Albert Y. Wu, MD, PhD, FACS

All Publications

• COVID-19 Recommendations From Ophthalmic and Plastic Reconstructive Surgery Societies Worldwide. Ophthalmic plastic and reconstructive surgery Nguyen, A. X., Gervasio, K. A., Wu, A. Y. 2020; 36 (4): 334?45

  Abstract

  PURPOSE: The COVID-19 pandemic has brought unprecedented challenges for oculoplastic surgeons worldwide, in terms of care delivery, medical equipment and at-risk patient management. To date, there are no centralized or compiled international COVID-19 guidelines for oculoplastic surgeons.METHODS: We examined COVID-19 guidelines published by oculoplastic societies worldwide. All countries around the world were initially considered in this study, but only 9 oculoplastic societies met the inclusion criteria: (1) publicly available guidelines displayed on the oculoplastic society's website, or (2) guidelines received from the oculoplastic society after contacting them twice using the contact information on their website.RESULTS: The 9 oculoplastic societies examined include: the American Society of Ophthalmic Plastic and Reconstructive Surgery, the British Oculoplastic Surgery Society, the Canadian Society of Oculoplastic Surgery, the European Society of Ophthalmic Plastic and Reconstructive Surgery, la Sociedad Espanola de Cirugia Plastica Ocular y Orbitaria, la Asociacion Colombiana de Cirugia Plastica Ocular, the Asia Pacific Society of Ophthalmic Plastic & Reconstructive Surgery, the Oculoplastics Association of India, and the Philippine Society of Ophthalmic Plastic and Reconstructive Surgery. They all agree that urgent procedures should not be delayed, while non-necessary procedures (including all elective clinic services) should be postponed. When adequate protective equipment is available, oculoplastic surgeons must treat urgent cases. Eight out of 9 societies have provided recommendations on personal protective equipment use in order to prevent the spread of COVID-19 and to adequately protect mucous membranes. Other recommendations provided by certain societies are related to shelter in place measures, hand hygiene and surface disinfection protocols, patient triage, and thyroid eye disease management.CONCLUSIONS: All 9 societies with published recommendations have provided valuable recommendations to their members, regarding urgency of care and infection control solutions (personal protective equipment, hand hygiene, telemedicine, and social isolation).

  View details for DOI 10.1097/IOP.0000000000001776

  View details for PubMedID 32658132

• Cannabis and the Cornea. Ocular immunology and inflammation Nguyen, A. X., Wu, A. Y. 2020: 1?6

  Abstract

  Purpose: While cannabis has the potential to reduce corneal pain, cannabinoids might induce side effects. This review article examines the effects of cannabinoids on the cornea. As more states and countries consider the legalization of adult cannabis use, health-care providers will need to identify ocular effects of cannabis consumption.Methods: Studies included in this review examined the connection between cannabis and the cornea, more specifically anti-nociceptive and anti-inflammatory actions of cannabinoids. NCBI Databases from 1781 up to December 2019 were consulted.Results: Five studies examined corneal dysfunctions caused by cannabis consumption (opacification, decreased endothelial cell density). Twelve studies observed a reduction in corneal pain and inflammation (less lymphocytes, decreased corneal neovascularization, increased cell proliferation and migration).Conclusion: More than half of the studies examined the therapeutic effects of cannabinoids on the cornea. As the field is still young, more studies should be conducted to develop safe cannabinoid treatments for corneal diseases.

  View details for DOI 10.1080/09273948.2020.1726969

  View details for PubMedID 32159404

• Differences in SARS-CoV-2 recommendations from major ophthalmology societies worldwide. BMJ open ophthalmology Nguyen, A. X., Gervasio, K. A., Wu, A. Y. 2020; 5 (1): e000525

  Abstract

  Objective: Since the WHO declared the COVID-19 outbreak as a public health emergency, medical societies around the world published COVID-19 recommendations to physicians to ensure patient care and physician safety. During this pandemic, ophthalmologists around the world adapted their clinical and surgical practice following such guidelines. This original research examines all publicly available COVID-19 recommendations from twelve major ophthalmology societies around the world.Methods and analysis: Twelve ophthalmology societies recognised by the International Council of Ophthalmology were included in this study. One society per each WHO region was included: the society selected was the one who had the highest number of national COVID-19 confirmed cases on 11 May 2020. In addition to these countries, the major ophthalmology society in each G7 country was included.Results: Ten out of 12 major international ophthalmology societies from countries covering all six WHO regions have given recommendations regarding urgent patient care, social distancing, telemedicine and personal protective equipment when caring for ophthalmic patients during the COVID-19 pandemic. While all guidelines emphasise the importance of postponing non-urgent care and taking necessary safety measures, specific recommendations differ between countries.Conclusions: As there is no clear consensus on ophthalmology guidelines across countries, this paper highlights the differences in international ophthalmic care recommendations during the COVID-19 pandemic. Knowledge of the differences in ophthalmic management plans will allow ophthalmologists and all eye care providers to consider the variety of international approaches and apply best practices following evidence-based recommendations during pandemics.

  View details for DOI 10.1136/bmjophth-2020-000525

  View details for PubMedID 32656359

• Training in and comfort with diagnosis and management of ophthalmic emergencies among emergency medicine physicians in the United States. Eye (London, England) Uhr, J. H., Governatori, N. J., Zhang, Q. E., Hamershock, R., Radell, J. E., Lee, J. Y., Tatum, J., Wu, A. Y. 2020

  Abstract

  Patients with ophthalmic emergencies often present to emergency rooms. Emergency medicine (EM) physicians should feel comfortable encountering these conditions. We assessed EM physicians' comfort working up, diagnosing, and managing ophthalmic emergencies.329 EM physicians participated in this cross-sectional multicentre survey. Questions inquired about the amount, type, and self-perceived adequacy of ophthalmic training. Likert scales were used to assess confidence and comfort working up, diagnosing, and managing ophthalmic emergencies.Participants recall receiving a median of 5 and 10?h of ophthalmic training in medical school and residency, respectively. Few feel this prepared them for residency (16.5%) or practice (52.0%). Only 50.6% feel confident with their ophthalmic exam. Most (75.0%) feel confident in their ability to identify an ophthalmic emergency, but 58.8% feel well prepared to work them up. Responders feel more comfortable diagnosing acute retrobulbar hematoma (72.5%), retinal detachment (69.8%), and acute angle closure glaucoma (78.0%) than central retinal artery occlusion (28.9%) or giant cell arteritis (53.2%). Only 60.2% feel comfortable determining if canthotomy and cantholysis is necessary in the setting of acute retrobulbar hematoma, and 40.3% feel comfortable performing the procedure. There was a trend towards attending physicians and providers in urban and academic settings feeling more comfortable diagnosing and managing ophthalmic emergencies compared to trainees, non-urban, and non-academic physicians.Many participants do not feel comfortable using ophthalmic equipment, performing an eye exam, making vision or potentially life-saving diagnoses, or performing vision-saving procedures, suggesting the need to increase ophthalmic training in EM curricula.

  View details for DOI 10.1038/s41433-020-0889-x

  View details for PubMedID 32350451

• "Percussive" orbital trauma from wooden drumstick. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie Garcia, G. A., Veerappan, M., Bair, H., Charlson, E. S., Wu, A. Y. 2020

  View details for DOI 10.1016/j.jcjo.2020.07.016

  View details for PubMedID 32818428

• Management and outcomes of proteasome inhibitor associated chalazia and blepharitis: a case series. BMC ophthalmology Sklar, B. A., Gervasio, K. A., Leng, S., Ghosh, A., Chari, A., Wu, A. Y. 2019; 19 (1): 110

  Abstract

  BACKGROUND: The purpose of this case series was to further characterize proteasome inhibitor associated chalazia and blepharitis, to investigate outcomes of different management strategies, and to propose a treatment algorithm for eyelid complications in this patient population.METHODS: This retrospective case series included sixteen patients found to have chalazia and/or blepharitis while receiving proteasome inhibitors for plasma cell disorders at Mount Sinai Hospital in New York, NY from January 2010 through January 2017. Main outcomes were complete resolution of eyelid complications and time to resolution. Student's t-test was used to compare average values and Fisher's exact test was used to compare proportions.RESULTS: Fourteen patients had chalazia and 10 had blepharitis. Chalazia averaged 5.4mm, and 11 patients with chalazia experienced two or more lesions. Median follow-up time was 17months. Average time from bortezomib exposure to onset of first eyelid complication was 3.4months. Chalazia episodes were more likely to completely resolve than blepharitis episodes (p=0.03). Ocular therapy alone was trialed for an average of 1.8months before proceeding to bortezomib omission. Average time to eyelid complication resolution using ocular therapy alone was 1.8months versus 3.1months after bortezomib omission. In this series, the combination of ocular therapy and bortezomib omission led to complete resolution of eyelid complications more often than ocular therapy alone.CONCLUSION: Proteasome inhibitor associated eyelid complications were identified in sixteen patients with plasma cell disorders. Eyelid complications may be treated with a 2-month trial of conservative ocular therapies alone, followed by continuation of ocular therapy in combination with bortezomib omission if eyelid signs persist.

  View details for DOI 10.1186/s12886-019-1118-x

  View details for PubMedID 31088416

• Association between cannabis and the eyelids: A comprehensive review. Clinical & experimental ophthalmology Nguyen, A. X., Wu, A. Y. 2019

  Abstract

  Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients. There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug. These include: ptosis induction, an "eyelid tremor" appearance and blepharospasm attenuation. Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors. Fourteen articles report eyelid tremors in intoxicated drivers and ptosis as a secondary effect in cannabinoid animal experimental models. The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear. Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/ceo.13687

  View details for PubMedID 31747112

• Review of Ocular Manifestations of Joubert Syndrome. Genes Wang, S. F., Kowal, T. J., Ning, K., Koo, E. B., Wu, A. Y., Mahajan, V. B., Sun, Y. 2018; 9 (12)

  Abstract

  Joubert syndrome is a group of rare disorders that stem from defects in a sensory organelle, the primary cilia. Affected patients often present with disorders involving multiple organ systems, including the brain, eyes, and kidneys. Common symptoms include breathing abnormalities, mental developmental delays, loss of voluntary muscle coordination, and abnormal eye movements, with a diagnostic "molar tooth" sign observed by magnetic resonance imaging (MRI) of the midbrain. We reviewed the ocular phenotypes that can be found in patients with Joubert syndrome. Ocular motor apraxia is the most frequent (80% of patients), followed by strabismus (74%) and nystagmus (72%). A minority of patients also present with ptosis (43%), chorioretinal coloboma (30%), and optic nerve atrophy (22%). Although mutations in 34 genes have been found to be associated with Joubert syndrome, retinal degeneration has been reported in only 38% of patients. Mutations in AHI1 and CEP290, genes critical to primary cilia function, have been linked to retinal degeneration. In conclusion, Joubert syndrome is a rare pleiotropic group of disorders with variable ocular presentations.

  View details for PubMedID 30518138

• Orbital Metastasis From Urothelial Carcinoma: A Comprehensive Literature Review. Ophthalmic plastic and reconstructive surgery Sklar, B. A., Gervasio, K. A., Karmazin, K., Wu, A. Y. 2018

  Abstract

  PURPOSE: To review the clinical features of orbital and choroidal metastases from urothelial carcinomas of the urinary tract among cases reported in the literature, and to describe a case of orbital metastasis from bladder cancer presenting as apparent internuclear ophthalmoplegia.METHODS: Case reports of orbital and choroidal metastases from urothelial carcinomas published in the literature from 1965 to 2018 were reviewed. Data collected included patient demographics, cancer stage and primary site, time to onset of ocular symptoms, length of presenting ocular symptoms, types of primary ocular symptoms, diagnostic imaging, histology, systemic and ocular treatments, and survival time.RESULTS: Twenty-eight cases of urothelial carcinoma with metastasis to the orbit or choroid were reviewed. Men were significantly more likely to suffer from this condition than women (p = 0.011). The average age of presentation with orbital symptoms was 63 years, with an average time of 19 months between primary cancer diagnosis and onset of orbital symptoms. Twenty-two patients had metastasis to the orbit and 6 to the choroid. In 4 cases, ocular deficits secondary to orbital and/or choroidal metastases were the initial presenting symptoms in patients with previously undiagnosed urothelial carcinoma. The most commonly noted primary ocular symptoms and signs consisted of decreased visual acuity, decreased ocular motility, proptosis, and diplopia. Average survival from onset of ocular symptoms was 4.67 months.CONCLUSIONS: Urothelial carcinoma may metastasize to the orbit or choroid; furthermore, its presentation may mimic internuclear ophthalmoplegia. It is recommended that any patient with visual symptoms and known urothelial cancer should undergo expedited workup for metastatic disease.

  View details for DOI 10.1097/IOP.0000000000001256

  View details for PubMedID 30489454

• RELATIONSHIP BETWEEN OBSTRUCTIVE SLEEP APNEA AND THE PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Chang, A. C., Fox, T. P., Wang, S., Wu, A. Y. 2018; 38 (11): 2197?2206

  Abstract

  To evaluate the relationship between obstructive sleep apnea (OSA) and the presence and severity of diabetic retinopathy (DR).Three hundred seventeen patients with International Classification of Diseases diagnoses of both DR and OSA were evaluated retrospectively. Diabetic retinopathy severity and diabetic macular edema status were determined by diagnostic coding and medical records. Obstructive sleep apnea severity and additional sleep measures were obtained from overnight polysomnography. Analysis was performed using multivariable logistic regression.After adjustment, an association was seen between DR and severe OSA (odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.14-4.18, P = 0.019). Proliferative DR was associated with severe OSA versus no DR (OR: 2.40, 95% CI: 1.12-5.14, P = 0.024) and mild nonproliferative DR (OR: 2.87, 95% CI: 1.26-6.55, P = 0.012). Comparing all nonproliferative DR with proliferative DR, proliferative DR and severe OSA were associated (OR: 2.20, 95% CI: 1.03-4.70, P = 0.043), as well as diabetic macular edema and severe OSA (OR: 2.89, 95% CI: 1.58-5.27, P = 0.001). No association was seen between DR/diabetic macular edema and secondary sleep measures.The findings suggest an increased risk of DR, proliferative DR, and diabetic macular edema in patients with severe OSA. Ophthalmologists following these patients should be aware of this association to better manage ocular sequelae of diabetes.

  View details for DOI 10.1097/IAE.0000000000001848

  View details for Web of Science ID 000454007400012

  View details for PubMedID 28937527

• Multi-electrode recording as a novel technique in electromyography of the orbicularis oculi muscle Sklar, B., Gervasio, K. A., Kaur, K., Sivak, M., Wu, A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912500290

• Surgical loupe usage among oculoplastic surgeons in North America CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE Wei, C., Wu, A. Y. 2018; 53 (2): 139?44

  Abstract

  To study the patterns of usage and perception among U.S. oculoplastic surgeons regarding surgical loupes.An anonymous 20-question survey was emailed out to the American Society of Ophthalmic Plastic and Reconstructive Surgery listserv. Data were compiled in Google Forms. SPSS was used for statistical analyses. This study was approved by the institutional review board.Of the 609 members contacted, 239 (39%) completed the survey; 95% of respondents owned loupes and 78% regularly used them. No association was observed between frequency of loupe usage and sex or years in practice. The most common magnification and brand were 2.5× and Designs for Vision, respectively. The most common problems associated with loupes were limited vision (33%) and lack of comfort (24%), with 11% citing neck and cervical spinal disorders. The most common benefits were magnification (93%) and increased visual accuracy (68%). Of the respondents, 56% believed improved patient care to be a benefit and 76% believed that loupes enhance surgical outcome. With regard to training, 67% supported incorporating loupes into residency, 35% believed in mandating loupe purchase, and 25% wanted residencies to provide loupes at no cost. Respondent support for the use of loupes in practice and training was directly correlated with how frequently they used loupes.The vast majority of respondents owned loupes. Although most loupe owners used loupes regularly, a sizable proportion operated with limited vision and lack of comfort. Overall, just over half of respondents believed that loupes improve patient care and should be integrated into residency.

  View details for PubMedID 29631825

• Conservative therapy for chalazia: is it really effective? Acta ophthalmologica Wu, A. Y., Gervasio, K. A., Gergoudis, K. N., Wei, C., Oestreicher, J. H., Harvey, J. T. 2018

  Abstract

  To assess the within-treatment efficacy of hot compresses (HC), HC plus tobramycin (Tobrex) and HC plus tobramycin/dexamethasone (Tobradex) for chalazia treatment.Design: Multicentre, randomized clinical trial (ClinicalTrials.gov identifier, NCT01230593).Two clinical sites in New York and two clinical sites in Ontario.A total of 149 patients with one or more chalazia on separate eyelids randomly assigned to receive HC (n = 50), HC plus tobramycin (n = 50) or HC plus tobramycin/dexamethasone (n = 49).4-6 weeks of assigned treatment. Patients were measured for chalazion horizontal width and surveyed for pain and treatment satisfaction levels.Primary outcome was complete resolution (100% size reduction). Secondary outcomes were size change in millimetres and patient reported pre- and post-treatment pain and satisfaction levels.In the intention-to-treat (ITT) population, complete resolution occurred in 36 (18%) lesions total, 13 (21%) treated with HC, 12 (16%) with HC plus tobramycin and 11 (18%) with HC plus tobramycin/dexamethasone, with no significant difference between them (p = .78). Individually by paired t-test, there were statistically significant post-treatment mean size differences: HC 1.20 mm (p < 0.001), HC plus tobramycin 1.69 mm (p < .001) and HC plus tobramycin/dexamethasone 1.54 mm (p < 0.001), but no significant difference between them (p = .61). Lesions that completely resolved had a statistically significant lower pretreatment duration (1.5 months) compared to lesions that did not completely resolve (2.2 months) (p = .04).Hot compresses (HC) alone or in combination with tobramycin or tobramycin/dexamethasone drops and ointment are all effective first-line treatment options for chalazia. However, physicians may consider moving directly to the use of more invasive therapies, such as incision and curettage or steroid injections, for chalazia that have been present for more than 2 months, as older lesions are less likely to resolve with conservative therapies alone.

  View details for PubMedID 29338124

• Novel Hormone Receptors Present in Apocrine Cystadenoma of the Eyelid OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY Brown, S. E., Friedman, A. H., Phelps, R. G., Bleiweiss, I. J., Wu, A. Y. 2017; 33 (1): E20-E21

  Abstract

  A 53-year-old woman presented with an apocrine cystadenoma of the right upper eyelid. Histologic examination revealed proliferating epithelial cells with apocrine snouts and occasional mitotic figures. Immunohistochemical analysis revealed a Ki-67 index of 15% and positive staining for synaptophysin, chromogranin, estrogen receptor, progesterone receptor, gross cystic disease fluid protein (GCDFP)-15, and mammoglobin. The complement of positive immunomarkers in this case reinforces the importance of total excision and careful histologic assessment.

  View details for DOI 10.1097/IOP.0000000000000416

  View details for Web of Science ID 000392250400028

  View details for PubMedID 25719370

• Healing comparison of porcine cutaneous incisions made with cold steel scalpel, standard electrosurgical blade, and a novel tissue dissector. Medical research and innovations Wu, A. Y., Baldwin, T. J., Patel, B. C., Clymer, J. W., Lewis, R. D. 2017; 1 (5)

  Abstract

  Standard electrosurgery provides superior hemostasis compared to a cold steel scalpel, but inferior tissue healing. A novel electrosurgical blade with an advanced waveform, the MEGADYNE ACE BLADE? 700 Soft Tissue Dissector (ACE), was designed to provide both excellent hemostasis and wound healing. This study compared ACE to scalpel and standard electrosurgery in a porcine model of wound healing.Skin incisions from six pigs were evaluated at time points of 0, 1, 2, 3 and 6 weeks after application of the three devices. Histopathology was performed on samples from each time point. For each non-initial time point, the healing incisions were photographed for later evaluation by expert graders, and excised for wound strength testing.Time 0 photomicrographs showed a gradient of thermal tissue damage by initial incision, ranging from no damage made by the scalpel, minimal damage made by ACE, and twice the ACE damage made by a nonstick PTFE-coated electrosurgical blade. Histopathologic analysis at 6 weeks showed comparable dermal scar width measurements for scalpel and ACE incisions. Scars were wider for incisions made by standard electrosurgical blade. Wound strength was greater for scalpel and ACE than for standard electrosurgery. Cosmetic results at 6 weeks were not significantly different between scalpel and ACE incisions, while standard electrosurgical blade incisions were significantly inferior to ACE (odds ratio: 53.4, p<0.001).The MEGADYNE ACE BLADE? 700 Soft Tissue Dissector represents a significant improvement in electrosurgical technology for skin incisions and dispels the traditional concerns of delayed healing and poor cosmetic result that have been attributed to using conventional electrosurgical blades for skin incisions.

  View details for DOI 10.15761/MRI.1000124

  View details for PubMedID 33073169

  View details for PubMedCentralID PMC7561048

• Gun trauma and ophthalmic outcomes. Eye (London, England) Chopra, N., Gervasio, K. A., Kalosza, B., Wu, A. Y. 2017

  Abstract

  PurposeThis retrospective cohort study assesses the visual outcomes of patients who survive gunshot wounds to the head.MethodsThe Elmhurst City Hospital Trauma Registry and Mount Sinai Data Warehouse were queried for gun trauma resulting in ocular injury over a 16-year period. Thirty-one patients over 16 years of age were found who suffered a gunshot wound to the head and resultant ocular trauma: orbital fracture, ruptured globe, foreign body, or optic nerve injury. Gun types included all firearms and air guns. Nine patients were excluded due to incorrect coding or unavailable charts. Statistical analysis was performed using a simple bivariate analysis (?2).ResultsOf the 915 victims of gun trauma to the head, 27 (3.0%) sustained ocular injuries. Of the 22 patients whose records were accessible, 18 survived. Eight of the 18 surviving patients (44%) suffered long-term visual damage, defined as permanent loss of vision in at least one eye to the level of counting fingers or worse. Neither location of injury (P=0.243), nor type of gun used (P=0.296), nor cause of gun trauma (P=0.348) predicted visual loss outcome. The Glasgow Coma Scale eye response score on arrival to the hospital also did not predict visual loss outcome (P=0.793).ConclusionThere has been a dearth of research into gun trauma and even less research on the visual outcomes following gun trauma. Our study finds that survivors of gun trauma to the head suffer long-term visual damage 44% of the time after injury.Eye advance online publication, 22 December 2017; doi:10.1038/eye.2017.249.

  View details for DOI 10.1038/eye.2017.249

  View details for PubMedID 29271420

• Applications of stem cell biology to oculoplastic surgery CURRENT OPINION IN OPHTHALMOLOGY Daniel, M. G., Wu, A. Y. 2016; 27 (5): 428-432

  Abstract

  The review examines the utility of stem cell biology in ophthalmology and oculoplastic surgery.The applicability of stem cell biology varies across a range of different subfields within ophthalmology and oculoplastic surgery. Resident stem cells have been identified in the lacrimal gland, corneal limbus, orbital fat, and muscles of the eye, and can potentially be applied for in-vitro cell and organ cultures with the intent of disease modeling and transplants. The discovery of adipocyte-derived stem cells offered a potentially powerful tool for a variety of oculoplastic applications, such as wound healing, skin rejuvenation, and burn therapeutics. Several groups are currently identifying new uses for stem cells in oculoplastic surgery.The need for stem cell treatment spans a wide array of subfields within ophthalmology, ranging from reconstruction of the eyelid to the generation of artificial lacrimal glands and oncological therapeutics. The advent of induced pluripotent stem cells opened the realm of regenerative medicine, making the modeling of patient-specific diseases a possibility. The identification and characterization of endogenous stem cell populations in the eye makes it possible to obtain specific tissues through induced pluripotent stem cells differentiation, permitting their use in transplants for oculoplastic surgery.

  View details for DOI 10.1097/ICU.0000000000000288

  View details for Web of Science ID 000382560300011

  View details for PubMedID 27206262

• Awareness and Knowledge of Emergent Ophthalmic Disease Among Patients in an Internal Medicine Clinic JAMA OPHTHALMOLOGY Uhr, J. H., Mishra, K., Wei, C., Wu, A. Y. 2016; 134 (4): 424-431

  Abstract

  Emergent ophthalmic disease can lead to permanent visual impairment or blindness if medical attention is delayed. Awareness and knowledge of emergent ophthalmic disease may be important for early medical presentation and maximization of visual prognosis in some cases.To assess public awareness and knowledge of 4 emergent ophthalmic diseases.This cross-sectional study was conducted from June 1 to July 30, 2015, in the waiting rooms of the outpatient internal medicine resident clinic at Mount Sinai Hospital. A written survey was administered to evaluate awareness and knowledge of retinal detachment, acute angle-closure glaucoma, giant cell arteritis, and central retinal artery occlusion. Awareness of each disease was assessed by whether participants knew what the diseases were (yes or no). Knowledge was evaluated by responses to 3 questions for each disease, including 1 question about basic pathophysiologic features, 1 question about basic symptoms, and 1 question about basic treatment options. All English-speaking patients who were physically and cognitively able to fill out the survey without assistance were considered eligible and offered the opportunity to participate during times of survey distribution; 237 completed the survey. Demographic information, including age, sex, race, income, and educational level, was collected. Data were assessed from August 1 to 7, 2015.Awareness of each ophthalmic disease was determined by the proportion of respondents who answered yes, and knowledge was determined by the proportion of aware respondents who answered the knowledge questions correctly.Two hundred thirty-seven patients (of 227 who gave complete demographic information, 76 men [33.5%], 151 women [66.5%], and mean [SD] age, 51.3 [16.8] years) completed the survey. Awareness of each of the diseases studied was low; 61 of 220 respondents (27.7%; 95% CI, 21.8%-33.6%) were aware of retinal detachment; 32 of 219 respondents (14.6%; 95% CI, 9.9%-19.3%), acute angle-closure glaucoma; 11 of 216 respondents (5.1%; 95% CI, 2.2%-8.0%), giant cell arteritis; and 10 of 218 respondents (4.6%; 95% CI, 1.8%-7.4%), central retinal artery occlusion. Respondents who were aware and knowledgeable ranged from 29 of 199 (14.6%) for the pathophysiologic features of retinal detachment, 1 of 208 (0.5%) for the symptoms and 2 of 203 (1.0%) for treatment of giant cell arteritis, and 1 of 193 (0.5%) for the pathophysiologic features of central retinal artery occlusion.Levels of awareness and knowledge of emergent ophthalmic diseases are low. These results indicate a need to educate the public about these acutely vision-threatening entities to ensure early medical presentation, to achieve the best possible visual prognosis, and to preserve quality of life.

  View details for DOI 10.1001/jamaophthalmol.2015.6212

  View details for Web of Science ID 000373988900019

  View details for PubMedID 26892039

• Corneal recovery in a rabbit limbal stem cell deficiency model by autologous grafts of tertiary outgrowths from cultivated limbal biopsy explants MOLECULAR VISION Selver, O. B., Durak, I., Gurdal, M., Baysal, K., Ates, H., Ozbek, Z., Wang, Z., Wu, A., Wolosin, J. M. 2016; 22: 138-149

  Abstract

  To determine the corneal regenerative capacity of sequentially generated primary, secondary, and tertiary limbal explant outgrowths in a limbal stem cell deficiency (LSCD) surgical model.Two-millimeter-long limbal shallow biopsies were surgically excised from the upper quadrant of the right eye of rabbits and set on preserved amniotic membrane for explant culture. After the generation of primary outgrowth, the biopsies were sequentially transferred to new amniotic membrane to generate secondary and then tertiary outgrowths. Eighteen rabbits were subjected to a 360° limbal peritomy extending into the scleral zone and combined with superficial keratectomy of the corneal periphery and thorough mechanical debridement of the central cornea in their left eye. Right eye outgrowths, six of each generation, were engrafted on the ocular surface. Clinical outcomes (neovascularization, corneal clarity, and corneal fluorescein staining) were graded after 6 months. Post-mortem corneas were compared with histology, immunochemistry for p63 and Krt3, ABCG2-dependent dye exclusion, and capacity for outgrowths in explant culture.Immunohistology and western blot of the outgrowths for p63 and Krt3 indicated no differences in expression between the primary and tertiary outgrowths for these two markers of growth and differentiation. Clinically, all rabbits treated with amniotic membrane alone developed severe LSCD. Most rabbits grafted with cell outgrowths from all three outgrowth generations achieved stable (>6 months) recovery of the ocular surface. There were partial failures of grafts performed with two secondary and tertiary outgrowths. However, Kruskal-Wallis statistical analysis of the clinical scores yielded no significant difference between the three groups (p=0.524). Histology showed full anatomic recovery of grafts made with primary and tertiary outgrowths. Krt3 and p63 expression throughout the whole limbal corneal epithelium with primary or tertiary outgrowths was not distinguishable from each other. The percentage of dye-excluding cells present within this zone and the capacity of the explant epithelial outgrowth of the regenerated peripheral corneal zone were also on par with those of the donor corneas. The Krt3-negative cells that characterize the basal epithelial layer of the normal limbus could not be found in any regenerated cornea from the primary to tertiary outgrowths.Our results demonstrate that in rabbits post-primary explant outgrowths retain the capacity for LSCD recovery found in primary explants.

  View details for Web of Science ID 000369699800001

  View details for PubMedID 26937166

  View details for PubMedCentralID PMC4757454

• Prognostic Value of Ocular Trauma Scores in Patients With Combined Open Globe Injuries and Facial Fractures AMERICAN JOURNAL OF OPHTHALMOLOGY Gervasio, K. A., Weinstock, B. M., Wu, A. Y. 2015; 160 (5): 882-888

  Abstract

  To assess the prognostic value of the Ocular Trauma Score in patients with combined open globe injuries and facial fractures.Retrospective cohort study.A comprehensive chart review was conducted on 25 patients (28 eyes) identified from the Elmhurst City Hospital Trauma Registry between January 1, 2000 and June 30, 2012. Elmhurst City Hospital is a level 1 trauma center located in Elmhurst, New York, USA.Average age was 52 (range 18-88) and patients were predominantly male (84%). The majority of patients had an Ocular Trauma Score of 1 (87.5%), and of these patients, 76% and 14% had final visual acuities of no light perception (NLP) and light perception/hand motion (LP/HM), respectively. These corresponded to 74% and 15% predicted by the original Ocular Trauma Score guidelines (100% sensitive and 100% specific). Ocular Trauma Score of 1 was associated with zone 3 eye wound location (P = .02). Independent of Ocular Trauma Score, initial visual acuity and frontal bone fractures were predictive of NLP (P = .006 and P = .047). Nonblindness was associated with nasal bone fractures (P = .047).This study validates the use of the Ocular Trauma Score in patients with combined facial fracture and open globe injury. The presence of facial fractures does not appear to influence visual prognosis for open globe injuries with an Ocular Trauma Score of 1. In the absence of data to calculate a full Ocular Trauma Score, initial visual acuity was the strongest predictor of final visual outcome.

  View details for DOI 10.1016/j.ajo.2015.08.007

  View details for Web of Science ID 000363914800006

  View details for PubMedID 26275473

• Diagnostic Delay and Amniotic Membrane Transplantation in a Child With Atypical Stevens-Johnson Syndrome. Journal of pediatric ophthalmology & strabismus Gervasio, K. A., Wu, A. Y. 2015; 52 Online: e41-4

  Abstract

  A 4-year-old boy presented with a 6-day history of severe non-limbic-sparing conjunctivitis. Atypical Stevens-Johnson syndrome with a possible cause of Mycoplasma pneumoniae was suspected as the precipitant of the clinical symptoms. The patient recovered with amniotic membrane transplantation and intravenous immunoglobulin therapy despite an initial delay in diagnosis.

  View details for DOI 10.3928/01913913-20150811-01

  View details for PubMedID 26301401

• Bilateral Lacrimal Gland Disease Clinical Features of 97 Cases OPHTHALMOLOGY Tang, S. X., Lim, R. P., Al-Dahmash, S., Blaydon, S. M., Cho, R. I., Choe, C. H., Connor, M. A., Durairaj, V. D., Eckstein, L. A., Hayek, B., Langer, P. D., Lelli, G. J., Mancini, R., Rabinovich, A., Servat, J., Shore, J. W., Sokol, J. A., Tsirbas, A., Wladis, E. J., Wu, A. Y., Shields, J. A., Shields, C., Shinder, R. 2014; 121 (10): 2040-?

  Abstract

  Bilateral lacrimal gland (LG) disease is a unique presentation that can result from varied causes. We reviewed the diagnoses, clinical features, and outcomes of 97 patients with this entity.Case series.Ninety-seven patients with bilateral LG disease.Retrospective review and statistical analysis using analysis of variance and the Fisher exact test.Patient demographics, clinical features, diagnostic testing, diagnosis, and treatment.Patient age ranging from 8 to 84 years (mean, 46 years). The predominant gender was female (77%), and race included black (49%), white (38%), and Hispanic (12%) patients. Diagnoses fell into 4 categories: inflammatory (n = 51; 53%), structural (n = 20; 21%), lymphoproliferative (n = 19; 20%), and uncommon (n = 7; 7%) entities. The most common diagnoses included idiopathic orbital inflammation (IOI; n = 29; 30%), sarcoidosis (n = 19; 20%), prolapsed LG (n = 15; 15%), lymphoma (n = 11; 11%), lymphoid hyperplasia (n = 8; 8%), and dacryops (n = 5; 5%). Inflammatory conditions were more likely in younger patients (P<0.05) and in those with pain (P<0.001) and mechanical blepharoptosis (P<0.01) at presentation, whereas lymphoma was more common in older patients (P<0.001) without active signs of inflammation at presentation. Black patients were more likely to have sarcoidosis (P<0.01). Laboratory results showed high angiotensin converting enzyme level being significantly more likely in patients with sarcoidosis (P<0.05). However, sensitivity was limited to 45%, with 25% of patients diagnosed with IOI also demonstrating positive results. Corticosteroid therapy was the treatment of choice in 38 cases, corresponding to resolution of symptoms in 29% and improvement in an additional 32%. Overall, chronic underlying disease was found in 71% of patients, among whom 26% achieved a disease-free state, whereas 3% succumbed to their underlying disease.The cause of bilateral lacrimal gland disease most commonly was inflammatory, followed by structural and lymphoproliferative. Patient characteristics and clinical presentations were key features distinguishing between competing possibilities. Despite local control with corticosteroids or radiotherapy, underlying disease continued in 71% of patients and led to death in 3%.

  View details for DOI 10.1016/j.ophtha.2014.04.018

  View details for Web of Science ID 000342697300036

  View details for PubMedID 24907059

• Enucleation versus evisceration in ocular trauma: a retrospective review and study of current literature. Orbit (Amsterdam, Netherlands) Zheng, C., Wu, A. Y. 2013; 32 (6): 356-361

  Abstract

  To compare variables and outcomes from ocular trauma leading to either enucleation or evisceration to better inform surgical decision making.Retrospective chart review.We reviewed 441 patients between 2001 and 2012 presenting with ocular trauma to a Level 1 trauma center in Queens, New York; of these, there were 16 enucleations and 6 eviscerations. Retrospective chart review noted age, gender, mechanism of injury, initial and final visual acuity, time to surgery, length of follow-up, pain, degree of motility, and complications. A review of literature in the context of our study was performed.20 patients were male and 2 patients were female; average age was 44 (SD: 20.0, range 18-91). 9/16 patients were enucleated to prevent sympathetic ophthalmia, whereas only 1/5 patient was eviscerated for this indication (p?=?0.1619). No cases of sympathetic ophthalmia were reported over an average follow-up of 316 days. Average length of follow-up varied significantly between the two groups, with an average of 370.4 days (SD: 566.9, range 0-1870) for enucleated eyes and 172.7 days (SD: 146.3, range 0-422) for eviscerated eyes (p?=?0.42). Medpor implants were preferred in eviscerations (5/6 eviscerations), whereas hydroxyapatite implants were preferred in enucleations (10/16 enucleations, p?=?0.04).Surgical decision-making in ocular trauma is largely based on surgeon preference and experience, with minimal evidence in the literature to support either enucleation or evisceration. We recommend evisceration over enucleation in cases of reliable patient follow-up due to the low incidence of sympathetic ophthalmia.

  View details for DOI 10.3109/01676830.2013.764452

  View details for PubMedID 23909276

• Idiopathic recurrent subconjunctival hemorrhage. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie Wu, A. Y., Kugathasan, K., Harvey, J. T. 2012; 47 (5): e28-9

  View details for DOI 10.1016/j.jcjo.2012.03.012

  View details for PubMedID 23036560

• A case of orbital involvement in IgG4-related disease. Orbit (Amsterdam, Netherlands) Teichman, J. C., Wu, A. Y., El-Shinnawy, I., Harvey, J. T. 2012; 31 (5): 327-329

  Abstract

  A 46-year-old male was referred to the Ophthalmology Service for a 7-year history of bilateral proptosis and a presumptive diagnosis of thyroid eye disease. Past medical history was only significant for autoimmune pancreatitis. All laboratory testing including tests of thyroid function were within normal limits. The patient underwent orbital biopsy and was found to have plasma cells containing mainly IgG4 immunoglobulin that was consistent with IgG4-related disease. The patient was treated with oral prednisone and the proptosis resolved within 3 weeks.

  View details for DOI 10.3109/01676830.2011.616618

  View details for PubMedID 22712681

• Cadaveric Anatomical Comparison of the Lateral Nasal Wall After External and Endonasal Dacryocystorhinostomy OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY Rootman, D., DeAngelis, D., Tucker, N., Wu, A., Hurwitz, J. 2012; 28 (2): 149-153

  Abstract

  Much literature has accumulated espousing the relative merits of endonasal and external dacryocystorhinostomy (DCR). However, there is comparatively little information on the relative anatomic differences between these 2 approaches. The purpose of this study is to investigate the anatomic relationships of the lateral nasal wall for endonasal and external DCR.Ten cadaver half heads were used in this study. Half were subject to endonasal and half to external DCR procedures. The lateral nasal wall was then dissected and measurements were taken of ostium and anastomosis size and position relative to other landmarks on the lateral nasal wall. Relationships were compared between the 2 procedures.The dimensions and area of the ostium and the anastomosis were similar between the 2 procedures. The lower portion of the ostium was located more inferiorly in endonasal DCR. Additionally, the ostium was more likely to be found lateral to the axilla of the middle turbinate in endonasal DCR, when compared with anterior for external. External DCR was also more likely to involve opening the anterior ethmoid air cells than endonasal approach.Endonasal and external DCR osteomies appear to be of similar size, with the endonasal opening being located slightly lower and more posterior on the lateral nasal wall.

  View details for DOI 10.1097/IOP.0b013e318248e687

  View details for Web of Science ID 000301974000025

  View details for PubMedID 22410664

• Endogenous bacterial endophthalmitis after routine colonoscopy CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE Wu, A. Y., Oestreicher, J. H. 2011; 46 (6): 556-557

  View details for DOI 10.1016/j.jcio.2011.10.002

  View details for Web of Science ID 000299017600027

  View details for PubMedID 22153651

• Bicanalicular Laceration Repair Via an Endoscopic Retrograde Approach OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY Wu, A. Y., Tucker, N. A. 2011; 27 (6): E165-E167

  Abstract

  A 31-year-old man presented 5 days after a left bicanalicular laceration from trauma. Identification of the medial cut ends under direct visualization was unsuccessful. A retrograde endoscopic approach was used to identify the common canaliculus or one of the medial cut ends of the canaliculi by injecting the lacrimal sac with saline and observing fluid egress from the wound. Both canaliculi were stented with a silicone tube and both ends of the tube were passed through the identified medial opening in the lacrimal sac. The tubes were retrieved from the nose and tied, and then left for 6 months before removal. The patient did not complain of epiphora and demonstrated bicanalicular patency on irrigation. This is the first description of using an endoscopic retrograde approach to identify the medial ends of a bicanalicular laceration.

  View details for DOI 10.1097/IOP.0b013e31820c6e3f

  View details for Web of Science ID 000296865200012

  View details for PubMedID 21346667

• Bifocal Orbital and Nasopharyngeal Amyloidomas Presenting as Graves Disease OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY Wu, A. Y., Chapman, W. B., Witterick, I. J., DeAngelis, D. D. 2011; 27 (5): E132-E134

  Abstract

  A 72-year-old man presented with a slowly progressive left hyperglobus, left infraduction deficit, bilateral lower eyelid retraction, and dysphagia. He had a notable chin-down head position, diplopia in primary position, and 3 mm of left proptosis. He had been diagnosed with Graves disease 3 years before presentation. CT scans showed enlargement of the left inferior and medial rectus muscles with associated stranding of the retrobulbar fat and a low-density heterogeneous mass in the left aspect of the neck protruding in the nasopharynx. Biopsies of the orbit and nasopharynx revealed focal areas of amyloid. This represents the first report of bifocal amyloidomas of the orbit and nasopharynx.

  View details for DOI 10.1097/IOP.0b013e31820367ca

  View details for Web of Science ID 000294711700012

  View details for PubMedID 21178798

• Indications for Orbital Imaging by the Oculoplastic Surgeon OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY Wu, A. Y., Jebodhsingh, K., Le, T., Law, C., Tucker, N. A., DeAngelis, D. D., Oestreicher, J. H., Harvey, J. T. 2011; 27 (4): 260-262

  Abstract

  To determine the indications for ordering orbital imaging and the indications for ordering CT versus MRI by oculoplastic surgeons and to assess the correlation between surgeon's clinical indications for imaging and the radiologist's diagnosis.Retrospective review of imaging requisitions and radiology reports.Patients of 4 oculoplastic surgeons who required CT or MRI scans.Imaging requisitions and radiology reports of patients from 4 oculoplastic surgeons were reviewed to determine the indication for ordering a CT or MRI scan between March 2006 and March 2009. The indications were then compared with the radiologist's diagnosis.A total of 735 patients were included: 449 (61.1%) female and 286 (38.9%) male, with an average age of 50.1 years and an age range of 7 months to 93 years. Of these patients, a total of 632 CT and 223 MRI scans were ordered, 135 of which were follow-up scans.The most common indication for CT scan was thyroid disease, followed by orbital tumors and then inflammatory disease, while the most common indication for MRI scan was orbital tumors, followed by inflammatory disease and then thyroid disease. CT scans were more commonly ordered than MRI, largely for trauma and to rule out orbital foreign body.

  View details for DOI 10.1097/IOP.0b013e31820b0365

  View details for Web of Science ID 000292633700022

  View details for PubMedID 21326128

• Enduragen patch grafts for exposed orbital implants. Orbit (Amsterdam, Netherlands) Wu, A. Y., Vagefi, M. R., Georgescu, D., Burroughs, J. R., Anderson, R. L. 2011; 30 (2): 92-95

  Abstract

  To present a new technique using the recently introduced Enduragen(®) material (Tissue Science Laboratories) as a patch graft for exposed ocular implants.A retrospective, interventional, non-comparative case series of 3 patients who had Enduragen patch grafts for the closure of Tenon's capsule and conjunctiva over exposed ocular implants. Medical records were reviewed and the following parameters were collected: age, gender, indication for surgery, type of surgery, laterality, type of orbital implant, complications after repair and length of follow-up.Three patients were identified, 2 males and 1 female. One patient had a secondary quad-motility implant with supertemporal exposure. The second patient had a secondary implant with a fistula at the lateral aspect of the socket. The third patient had a centrally exposed primary hydroxyapatite implant. All patients received Enduragen patch grafts to cover the implant. Follow up ranged from 40 to 43 months (mean, 41.3 months; SD, ± 1.5). None of the 3 patients had any signs of implant re-exposure at the time of the last post-operative visit. There were no intra-operative or early complications observed.This consecutive case series suggests that Enduragen could be used as a safe and effective patch graft for exposed ocular implants. However, a larger prospective study with longer follow-up would be useful in further defining the indications and limitations of the Enduragen patch graft for the treatment of exposed orbital implants.

  View details for DOI 10.3109/01676830.2011.558974

  View details for PubMedID 21438730

• Eyelash Resection Procedure for Severe, Recurrent, or Segmental Cicatricial Entropion OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY Wu, A. Y., Thakker, M. M., Wladis, E. J., Weinberg, D. A. 2010; 26 (2): 112-116

  Abstract

  To study the safety, efficacy, and cosmetic outcome of the eyelash resection procedure for treatment of severe, recurrent, or segmental cicatricial entropion.Retrospective consecutive case series of patients with severe, recurrent, or segmental cicatricial entropion treated with eyelash resection at the Moran Eye Center and the University of Vermont. Investigators performed chart reviews of these patients and evaluated effectiveness of the treatment and outcome data, including age, gender, diagnoses, method of repair, recurrence of trichiasis, and cosmetic satisfaction. There were no exclusionary characteristics specified in the study.A total of 26 eyelids were operated on in 5 male and 11 female patients. The mean age was 74 years, with the following diagnoses: idiopathic (6), ocular cicatricial pemphigoid (2), postoperative (2), ocular pseudopemphigoid (drug related) (1), graft-versus-host disease (1), Stevens-Johnson syndrome (1), trachoma (1), linear IgA bullous dermatosis (1), and trauma (1). Mean postoperative follow-up was 13 months. The functional success rate was 90.5%, and the cosmetic success rate was 100%.The eyelash resection procedure is a safe, effective, and cosmetically acceptable procedure for treatment of severe, recurrent, or segmental cicatricial entropion.

  View details for DOI 10.1097/IOP.0b013e3181b8c900

  View details for Web of Science ID 000276129300011

  View details for PubMedID 20305511

• Low-cost headlamps for facial and oculoplastic surgery OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY Wu, A. Y., Vagefi, M. R., Georgescu, D., McCann, J. D., Anderson, R. L. 2008; 24 (5): 429-429

  View details for Web of Science ID 000259652900028

  View details for PubMedID 18806679

• Molecular determinants for cyclic nucleotide binding to the regulatory domains of phosphodiesterase 2A JOURNAL OF BIOLOGICAL CHEMISTRY Wu, A. Y., Tang, X. B., Martinez, S. E., Ikeda, K., Beavo, J. A. 2004; 279 (36): 37928-37938

  Abstract

  Binding of cGMP to the GAF-B domain of phosphodiesterase 2A allosterically activates catalytic activity. We report here a series of mutagenesis studies on the GAF-B domain of PDE2A that support a novel mechanism for molecular recognition of cGMP. Alanine mutations of Phe-438, Asp-439, and Thr-488, amino acids that interact with the pyrimidine ring, decrease cGMP affinity slightly but increase cAMP affinity by up to 8-fold. Each interaction is required to provide for cAMP/cGMP specificity. Mutations of any of the residues that interact with the phosphate-ribose moiety or the imidazole ring abolish cGMP binding. Thus, residues that interact with the pyrimidine ring collectively control cAMP/cGMP specificity, whereas residues that bind the phosphate-ribose moiety and imidazole ring are critical for high affinity binding. Similar decreases in binding were found for mutations made in a bacterially expressed GAF-A/B plus catalytic domain construct. Because these constructs had very high catalytic activity, it appears that these mutations did not cause a global denaturation. The affinities of cAMP and cGMP for wild-type GAF-B alone were approximately 4-fold greater than for the holoenzyme, suggesting that the presence of neighboring domains alters the conformation of GAF-B. More importantly, the PDE2A GAF-B, GAF-A/B, GAF-A/B+C domains, and holoenzyme all bind cGMP with much higher affinity than has previously been reported. This high affinity suggests that cGMP binding to PDE2 GAF-B activates the enzyme rapidly, stoichiometrically, and in an all or none fashion, rather than variably over a large range of cyclic nucleotide concentrations.

  View details for DOI 10.1074/jbc.M404287200

  View details for Web of Science ID 000223554600086

  View details for PubMedID 15210692

• The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Martinez, S. E., Wu, A. Y., Glavas, N. A., Tang, X. B., Turley, S., Hol, W. G., Beavo, J. A. 2002; 99 (20): 13260-13265

  Abstract

  Cyclic nucleotide phosphodiesterases (PDEs) regulate all pathways that use cGMP or cAMP as a second messenger. Five of the 11 PDE families have regulatory segments containing GAF domains, 3 of which are known to bind cGMP. In PDE2 binding of cGMP to the GAF domain causes an activation of the catalytic activity by a mechanism that apparently is shared even in the adenylyl cyclase of Anabaena, an organism separated from mouse by 2 billion years of evolution. The 2.9-A crystal structure of the mouse PDE2A regulatory segment reported in this paper reveals that the GAF A domain functions as a dimerization locus. The GAF B domain shows a deeply buried cGMP displaying a new cGMP-binding motif and is the first atomic structure of a physiological cGMP receptor with bound cGMP. Moreover, this cGMP site is located well away from the region predicted by previous mutagenesis and structural genomic approaches.

  View details for DOI 10.1073/pnas.192374899

  View details for Web of Science ID 000178391700137

  View details for PubMedID 12271124

  View details for PubMedCentralID PMC130621

• Opposing effects of reactive oxygen species and cholesterol on endothelial nitric oxide synthase and endothelial cell caveolae CIRCULATION RESEARCH Peterson, T. E., Poppa, V., Ueba, H., Wu, A., Yan, C., Berk, B. C. 1999; 85 (1): 29-37

  Abstract

  Synthesis of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) is critical for normal vascular homeostasis. eNOS function is rapidly regulated by agonists and blood flow and chronically by factors that regulate mRNA stability and gene transcription. Recently, localization of eNOS to specialized plasma membrane invaginations termed caveolae has been proposed to be required for maximal eNOS activity. Because caveolae are highly enriched in cholesterol, and hypercholesterolemia is associated with increased NO production, we first studied the effects of cholesterol loading on eNOS localization and NO production in cultured bovine aortic endothelial cells (BAECs). Caveolae-enriched fractions were prepared by OptiPrep gradient density centrifugation. Treatment of BAECs with 30 microgram/mL cholesterol for 24 hours stimulated significant increases in total eNOS protein expression (1.50-fold), eNOS associated with caveolae-enriched membranes (2.23-fold), and calcium ionophore-stimulated NO production (1.56-fold). Because reactive oxygen species (ROS) contribute to endothelial dysfunction in hypercholesterolemia, we next studied the effects of ROS on eNOS localization and caveolae number. Treatment of BAECs for 24 hours with 1 micromol/L LY83583, a superoxide-generating napthoquinolinedione, decreased caveolae number measured by electron microscopy and prevented the cholesterol-mediated increases in eNOS expression. In vitro exposure of caveolae-enriched membranes to ROS (xanthine plus xanthine oxidase) dissociated caveolin more readily than eNOS from the membranes. These results show that cholesterol treatment increases eNOS expression, whereas ROS treatment decreases eNOS expression and the association of eNOS with caveolin in caveolae-enriched membranes. Our data suggest that oxidative stress modulates endothelial function by regulating caveolae formation, eNOS expression, and eNOS-caveolin interactions.

  View details for Web of Science ID 000081424900006

  View details for PubMedID 10400908

• Agonist induced homologous desensitization of mu-opioid receptors mediated by G protein-coupled receptor kinases is dependent on agonist efficacy MOLECULAR PHARMACOLOGY Kovoor, A., Celver, J. P., Wu, A., Chavkin, C. 1998; 54 (4): 704-711

  Abstract

  Using Xenopus laevis oocytes coexpressing mammalian mu-opioid receptors (MORs), beta-adrenergic receptor kinase 2 (beta-ARK2) [also called G protein-coupled receptor kinase (GRK3)], and beta-arrestin 2 (beta-arr 2), we compared the rates of beta-ARK2 (GRK3)- and beta-arr 2-mediated homologous receptor desensitization produced by treatment with opioid agonists of different efficacies. The response to MOR activation was measured using two-electrode voltage clamp as an increase in the conductance of the coexpressed G protein-coupled inwardly rectifying potassium (heteromultimer of KIR3.1 and KIR3.4) channels. Treatment with opioids of high efficacy, either [D-Ala2,N-MePhe4,Gly-ol5]-enkephalin, fentanyl, or sufentanyl, produced a GRK3- and beta-arr 2-dependent reduction in response in <20 min, whereas treatment with the partial agonist morphine produced receptor desensitization at a significantly slower rate. Because GRK3 requires activation and membrane targeting by free G protein betagamma subunits released after agonist-mediated activation of G proteins, a low efficacy agonist such as morphine may produce weak receptor desensitization as a consequence of poor GRK3 activation. To address this hypothesis, we substituted GRK5, a GRK that does not require activation by G protein betagamma. In oocytes expressing GRK5 instead of GRK3, both [D-Ala2,N-MePhe4, Gly-ol5]enkephalin and fentanyl, but not morphine, produced desensitization of MOR-activated potassium conductance. Thus, mu-opioid agonists produced significant receptor desensitization, mediated by either GRK3 or GRK5, at a rate dependent on agonist efficacy.

  View details for Web of Science ID 000076485500014

  View details for PubMedID 9765514