Originally from India, Ankush completed his Bachelors in Pharmacy from Guru Nanak Dev University in 2009. He completed his Masters in 2011 from McGill University, Montreal, Canada where he worked on investigating the role of intermediates of carbohydrate metabolism in regulating retinal angiogenesis. Furthermore, he obtained his PhD from Faculty of Medicine, McGill University in 2016 under the mentorship of Dr. Sylvain Chemtob.

His graduate research focus revolved around investigating the role of intermediates of carbohydrate metabolism and orphan GPCRs in modulation of the following:
1) Angiogenesis/Retinal vascular development in Retinopathy of Prematurity (ROP)
2) Modulation of inflammation during Preterm Labor
3) Regulation of Brain angiogenesis and rescue after post hypoxic-ischemic Brain injury

He received a couple of scholarships during his stint at McGill including CIHR-DDTP, CIHR-SBTP, FRSQ-VHRN scholarship and Graduate Provost Scholarship. He worked as a Biomarkers Scientist at Charles Rivers Laboratories, one of the leading CRO's for a year after his PhD. Ankush recently joined Department of Ophthalmology, Stanford University as a Post Doctoral Researcher under the guidance of Dr. Jeffery Goldberg.

Professional Education

  • PhD, McGill University, Pharmacology/Ophthalmology (2017)
  • Masters, McGill University, Pharmacology & Therapeutics (2012)
  • BPharm, Guru Nanak Dev University, Pharmaceutical Sciences (BPharm) (2009)


All Publications

  • Opposing Effects of Growth and Differentiation Factors in Cell-Fate Specification. Current biology : CB Chang, K. C., Sun, C., Cameron, E. G., Madaan, A., Wu, S., Xia, X., Zhang, X., Tenerelli, K., Nahmou, M., Knasel, C. M., Russano, K. R., Hertz, J., Goldberg, J. L. 2019


    Following ocular trauma or in diseases such as glaucoma, irreversible vision loss is due to the death of retinal ganglion cell (RGC) neurons. Although strategies to replace these lost cells include stem cell replacement therapy, few differentiated stem cells turn into RGC-like neurons. Understanding the regulatory mechanisms of RGC differentiation inávivo may improve outcomes of cell transplantation by directing the fate of undifferentiated cells toward mature RGCs. Here, we report a new mechanism by which growth and differentiation factor-15 (GDF-15), a ligand in the transforming growth factor-beta (TGF-?) superfamily, strongly promotes RGC differentiation in the developing retina inávivo in rodent retinal progenitor cells (RPCs) and in human embryonic stem cells (hESCs). This effect is in direct contrast to the closely related ligand GDF-11, which suppresses RGC-fate specification. We find these opposing effects are due in part to GDF-15's ability to specifically suppress Smad-2, but not Smad-1, signaling induced by GDF-11, which can be recapitulated by pharmacologic or genetic blockade of Smad-2 inávivo to increase RGC specification. No other retinal cell types were affected by GDF-11 knockout, but a slight reduction in photoreceptor cells was observed by GDF-15 knockout in the developing retina inávivo. These data define a novel regulatory mechanism of GDFs' opposing effects and their relevance in RGC differentiation and suggest a potential approach for advancing ESC-to-RGC cell-based replacement therapies.

    View details for DOI 10.1016/j.cub.2019.05.011

    View details for PubMedID 31155355

  • Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny SCIENTIFIC REPORTS Beaudry-Richard, A., Nadeau-Vallee, M., Prairie, E., Maurice, N., Heckel, E., Nezhady, M., Pundir, S., Madaan, A., Boudreault, A., Hou, X., Quiniou, C., Sierra, E., Beaulac, A., Lodygensky, G., Robertson, S. A., Keelan, J., Adams-Waldorf, K., Olson, D. M., Rivera, J., Lubell, W. D., Joyal, J., Bouchard, J., Chemtob, S. 2018; 8: 11875


    Antenatal inflammation as seen with chorioamnionitis is harmful to foetal/neonatal organ development including to eyes. Although the major pro-inflammatory cytokine IL-1? participates in retinopathy induced by hyperoxia (a predisposing factor to retinopathy of prematurity), the specific role of antenatal IL-1? associated with preterm birth (PTB) in retinal vasculopathy (independent of hyperoxia) is unknown. Using a murine model of PTB induced with IL-1? injection in utero, we studied consequent retinal and choroidal vascular development; in this process we evaluated the efficacy of IL-1R antagonists. Eyes of foetuses exposed only to IL-1? displayed high levels of pro-inflammatory genes, and a persistent postnatal infiltration of inflammatory cells. This prolonged inflammatory response was associated with: (1) a marked delay in retinal vessel growth; (2) long-lasting thinning of the choroid; and (3) long-term morphological and functional alterations of the retina. Antenatal administration of IL-1R antagonists - 101.10 (a modulator of IL-1R) more so than Kineret (competitive IL-1R antagonist) - prevented all deleterious effects of inflammation. This study unveils a key role for IL-1?, a major mediator of chorioamnionitis, in causing sustained ocular inflammation and perinatal vascular eye injury, and highlights the efficacy of antenatal 101.10 to suppress deleterious inflammation.

    View details for DOI 10.1038/s41598-018-30087-4

    View details for Web of Science ID 000440985100017

    View details for PubMedID 30089839

    View details for PubMedCentralID PMC6082873

  • Review of the mechanisms and therapeutic avenues for retinal and choroidal vascular dysfunctions in retinopathy of prematurity ACTA PAEDIATRICA Rivera, J. C., Madaan, A., Zhou, T. E., Chemtob, S. 2016; 105 (12): 1421-1433


    Retinopathy of prematurity (ROP) is a multifactorial disease and the main cause of visual impairment and blindness in premature neonates. The inner retina has been considered the primary region affected in ROP, but choroidal vascular degeneration and progressive outer retinal dysfunctions have also been observed. This review focuses on observations regarding neurovascular dysfunctions in both the inner and outer immature retina, the mechanisms and the neuronal-derived factors implicated in the development of ROP, as well potential therapeutic avenues for this disorder.Alterations in the neurovascular integrity of the inner and outer retina contribute to the development of ROP.

    View details for DOI 10.1111/apa.13586

    View details for Web of Science ID 000387793000026

    View details for PubMedID 27620714

  • Antenatal Suppression of IL-1 Protects against Inflammation-Induced Fetal Injury and Improves Neonatal and Developmental Outcomes in Mice JOURNAL OF IMMUNOLOGY Nadeau-Vallee, M., Chin, P., Belarbi, L., Brien, M., Pundir, S., Berryer, M. H., Beaudry-Richard, A., Madaan, A., Sharkey, D. J., Lupien-Meilleur, A., Hou, X., Quiniou, C., Beaulac, A., Boufaied, I., Boudreault, A., Carbonaro, A., Ngoc-Duc Doan, N. D., Joyal, J., Lubell, W. D., Olson, D. M., Robertson, S. A., Girard, S., Chemtob, S. 2017; 198 (5): 2047-2062


    Preterm birth (PTB) is commonly accompanied by in utero fetal inflammation, and existing tocolytic drugs do not target fetal inflammatory injury. Of the candidate proinflammatory mediators, IL-1 appears central and is sufficient to trigger fetal loss. Therefore, we elucidated the effects of antenatal IL-1 exposure on postnatal development and investigated two IL-1 receptor antagonists, the competitive inhibitor anakinra (Kineret) and a potent noncompetitive inhibitor 101.10, for efficacy in blocking IL-1 actions. Antenatal exposure to IL-1? induced Tnfa, Il6, Ccl2, Pghs2, and Mpges1 expression in placenta and fetal membranes, and it elevated amniotic fluid IL-1?, IL-6, IL-8, and PGF2?, resulting in PTB and marked neonatal mortality. Surviving neonates had increased Il1b, Il6, Il8, Il10, Pghs2, Tnfa, and Crp expression in WBCs, elevated plasma levels of IL-1?, IL-6, and IL-8, increased IL-1?, IL-6, and IL-8 in fetal lung, intestine, and brain, and morphological abnormalities: e.g., disrupted lung alveolarization, atrophy of intestinal villus and colon-resident lymphoid follicle, and degeneration and atrophy of brain microvasculature with visual evoked potential anomalies. Late gestation treatment with 101.10 abolished these adverse outcomes, whereas Kineret exerted only modest effects and no benefit for gestation length, neonatal mortality, or placental inflammation. In a LPS-induced model of infection-associated PTB, 101.10 prevented PTB, neonatal mortality, and fetal brain inflammation. There was no substantive deviation in postnatal growth trajectory or adult body morphometry after antenatal 101.10 treatment. The results implicate IL-1 as an important driver of neonatal morbidity in PTB and identify 101.10 as a safe and effective candidate therapeutic.

    View details for DOI 10.4049/jimmunol.1601600

    View details for Web of Science ID 000395904000030

    View details for PubMedID 28148737

  • ). American journal of obstetrics and gynecology Madaan, A., Nadeau-VallÚe, M., Rivera, J. C., Obari, D., Hou, X., Sierra, E. M., Girard, S., Olson, D. M., Chemtob, S. 2017; 216 (1): 60 e1-60 e17


    Uterine inflammatory processes trigger prolabor pathways and orchestrate on-time labor onset. Although essential for successful labor, inflammation needs to be regulated to avoid uncontrolled amplification and resolve postpartum. During labor, myometrial smooth muscle cells generate ATP mainly via anaerobic glycolysis, resulting in accumulation of lactate. Aside from its metabolic function, lactate has been shown to activate a G protein-coupled receptor, GPR81, reported to regulate inflammation. We therefore hypothesize that lactate produced during labor may act via GPR81 in the uterus to exert in a feedback manner antiinflammatory effects, to resolve or mitigate inflammation.We sought to investigate the role of lactate produced during labor and its receptor, GPR81, in regulating inflammation in the uterus.We investigated the expression of GPR81 in the uterus and the pharmacological role of lactate acting via GPR81 during labor, using shRNA-GPR81 and GPR81(-/-) mice.(1) Uterine lactate levels increased substantially from 2 to 9 mmol/L during labor. (2) Immunohistological analysis revealed expression of GPR81 in the uterus with high expression in myometrium. (3) GPR81 expression increased during gestation, and peaked near labor. (4) In primary myometrial smooth muscle cell and exávivo uteri from wild-type mice, lactate decreased interleukin-1?-induced transcription of key proinflammatory Il1b, Il6, Ccl2, and Pghs2; suppressive effects of lactate were not observed in cells and tissues from GPR81(-/-) mice. (5) Conversely, proinflammatory gene expression was augmented in the uterus at term in GPR81(-/-) mice and wild-type mice treated intrauterine with lentiviral-encoded shRNA-GPR81; GPR81 silencing also induced proinflammatory gene transcription in the uterus when labor was induced by endotoxin (lipopolysaccharide). (6) Importantly, administration to pregnant mice of a metabolically stable specific GPR81 agonist, 3,5-dihydroxybenzoic acid, decreased endotoxin-induced uterine inflammation, preterm birth, and associated neonatal mortality.Collectively, our data uncover a novel link between the anaerobic glycolysis and the control of uterine inflammation wherein the high levels of lactate produced during labor act on uterine GPR81 to down-regulate key proinflammatory genes. This discovery may represent a novel feedback mechanism to regulate inflammation during labor, and conveys a potential rationale for the use of GPR81 agonists to attenuate inflammation and resulting preterm birth.

    View details for DOI 10.1016/j.ajog.2016.09.072

    View details for PubMedID 27615440

  • Tetrahydrobiopterin (BH4) deficiency is associated with augmented inflammation and microvascular degeneration in the retina. Journal of neuroinflammation Rivera, J. C., Noueihed, B., Madaan, A., Lahaie, I., Pan, J., Belik, J., Chemtob, S. 2017; 14 (1): 181


    Tetrahydrobiopterin (BH4) is an essential cofactor in multiple metabolic processes and plays an essential role in maintaining the inflammatory and neurovascular homeostasis. In this study, we have investigated the deleterious effects of BH4 deficiency on retinal vasculature during development.hph-1 mice, which display deficiency in BH4 synthesis, were used to characterize the inflammatory effects and the integrity of retinal microvasculature. BH4 levels in retinas from hph-1 and wild type ?(WT)? mice were measured by LC-MS/MS. Retinal microvascular area and microglial cells number were quantified in hph-1 and WT miceáat different ages. Retinal expression of pro-inflammatory, anti-angiogenic, and neuronal-derived factors was analyzed by qPCR. BH4 supplementation was evaluated in vitro, ex-vivo, and in vivo models.Our findings demonstrated that BH4 levels in the retina from hph-1 mice were significantly lower by ~?90% at all ages analyzed compared to WTámice. Juvenile hph-1 mice showed iris atrophy, persistent fetal vasculature, significant increase in the number of microglial cells (pá<á0.01), as well as a marked degeneration of theáretinal microvasculature. Retinal microvascular alterations in juvenile hph-1 mice were associated with a decreased expression in Norrin (0.2-fold) and its receptor Frizzled-4 (FZD4; 0.51-fold), as well as with an augmented expression of pro-inflammatory factors such as IL-6 (3.2-fold), NRLP-3 (4.4-fold), IL-1? (8.6-fold), and the anti-angiogenic factor thrombospondin-1 (TSP-1; 17.5-fold). We found that TSP-1 derived from activated microglial cells is a factor responsible of inducing microvascular degeneration, but BH4 supplementation markedly prevented hyperoxia-induced microglial activation in vitro and microvascular injury in an ex-vivo model of microvascular angiogenesis and an in vivo model of oxygen-induced retinopathy (OIR).Our findings reveal that BH4 is a key cofactor in regulating the expression of inflammatory and anti-angiogenic factors that play an important function in the maintenance of retinal microvasculature.

    View details for DOI 10.1186/s12974-017-0955-x

    View details for PubMedID 28874201

  • Uterotonic Neuromedin U Receptor 2 and Its Ligands Are Upregulated by Inflammation in Mice and Humans, and Elicit Preterm Birth. Biology of reproduction Nadeau-VallÚe, M., Boudreault, A., Leimert, K., Hou, X., Obari, D., Madaan, A., Rouget, R., Zhu, T., Belarbi, L., Brien, M., Beaudry-Richard, A., Olson, D. M., Girard, S., Chemtob, S. 2016; 95 (3): 72-?


    Uterine labor requires the conversion of a quiescent (propregnancy) uterus into an activated (prolabor) uterus, with increased sensitivity to endogenous uterotonic molecules. This activation is induced by stressors, particularly inflammation in term and preterm labor. Neuromedin U (NmU) is a neuropeptide known for its uterocontractile effects in rodents. The objective of the study was to assess the expression and function of neuromedin U receptor 2 (NmU-R2) and its ligands NmU and the more potent neuromedin S (NmS) in gestational tissues, and the possible implication of inflammatory stressors in triggering this system. Our data show that NmU and NmS are uterotonic ex vivo in murine tissue, and they dose-dependently trigger labor by acting specifically via NmU-R2. Expression of NmU-R2, NmU, and NmS is detected in murine and human gestational tissues by immunoblot, and the expression of NmS in placenta and of NmU-R2 in uterus increases considerably with gestation age and labor, which is associated with amplified NmU-induced uterocontractile response in mice. NmU- and NmS-induced contraction is associated with increased NmU-R2-coupled Ca(++) transients, and Akt and Erk activation in murine primary myometrial smooth muscle cells (mSMCs), which are potentiated with gestational age. NmU-R2 is upregulated in vitro in mSMCs and in vivo in uterus in response to proinflammatory interleukin 1beta (IL1beta), which is associated with increased NmU-induced uterocontractile response and Ca(++) transients in murine and human mSMCs; additionally, placental NmS is markedly upregulated in vivo in response to IL1beta. In human placenta at term, immunohistological analysis revealed NmS expression primarily in cytotrophoblasts; furthermore, stimulation with lipopolysaccharide (LPS; Gram-negative endotoxin) markedly upregulates NmS expression in primary human cytotrophoblasts isolated from term placentas. Correspondingly, decidua of women with clinical signs of infection who delivered preterm display significantly higher expression of NmS compared with those without infection. Importantly, in vivo knockdown of NmU-R2 prevents LPS-triggered preterm birth in mice and the associated neonatal mortality. Altogether, our data suggest a critical role for NmU-R2 and its ligands NmU and NmS in preterm labor triggered by infection. We hereby identify NmU-R2 as a relevant target for preterm birth.

    View details for PubMedID 27512149

    View details for PubMedCentralID PMC5394981

  • Novel Noncompetitive IL-1 Receptor-Biased Ligand Prevents Infection-and Inflammation-Induced Preterm Birth JOURNAL OF IMMUNOLOGY Nadeau-Vallee, M., Quiniou, C., Palacios, J., Hou, X., Erfani, A., Madaan, A., Sanchez, M., Leimert, K., Boudreault, A., Duhamel, F., Rivera, J. C., Zhu, T., Noueihed, B., Robertson, S. A., Ni, X., Olson, D. M., Lubell, W., Girard, S., Chemtob, S. 2015; 195 (7): 3402-3415


    Preterm birth (PTB) is firmly linked to inflammation regardless of the presence of infection. Proinflammatory cytokines, including IL-1?, are produced in gestational tissues and can locally upregulate uterine activation proteins. Premature activation of the uterus by inflammation may lead to PTB, and IL-1 has been identified as a key inducer of this condition. However, all currently available IL-1 inhibitors are large molecules that exhibit competitive antagonism properties by inhibiting all IL-1R signaling, including transcription factor NF-?B, which conveys important physiological roles. We hereby demonstrate the efficacy of a small noncompetitive (all-d peptide) IL-1R-biased ligand, termed rytvela (labeled 101.10) in delaying IL-1?-, TLR2-, and TLR4-induced PTB in mice. The 101.10 acts without significant inhibition of NF-?B, and instead selectively inhibits IL-1R downstream stress-associated protein kinases/transcription factor c-jun and Rho GTPase/Rho-associated coiled-coil-containing protein kinase signaling pathways. The 101.10 is effective at decreasing proinflammatory and/or prolabor genes in myometrium tissue and circulating leukocytes in all PTB models independently of NF-?B, undermining NF-?B role in preterm labor. In this work, biased signaling modulation of IL-1R by 101.10 uncovers a novel strategy to prevent PTB without inhibiting NF-?B.

    View details for DOI 10.4049/jimmunol.1500758

    View details for Web of Science ID 000361741200046

    View details for PubMedID 26304990

  • Microglia and Interleukin-1 in Ischemic Retinopathy Elicit Microvascular Degeneration Through Neuronal Semaphorin-3A ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY Rivera, J. C., Sitaras, N., Noueihed, B., Hamel, D., Madaan, A., Zhou, T., Honore, J., Quiniou, C., Joyal, J., Hardy, P., Sennlaub, F., Lubell, W., Chemtob, S. 2013; 33 (8): 1881-1891


    Proinflammatory cytokines contribute to the development of retinal vasculopathies. However, the role of these factors and the mechanisms by which they elicit their effects in retina are not known. We investigated whether activated microglia during early stages of ischemic retinopathy produces excessive interleukin-1? (IL-1?), which elicits retinal microvascular degeneration not directly but rather by triggering the release of the proapoptotic/repulsive factor semaphorin-3A (Sema3A) from neurons.Sprague Dawley rats subjected to retinopathy induced by hyperoxia (80% O2; O2-induced retinopathy) exhibited retinal vaso-obliteration associated with microglial activation, NLRP3 upregulation, and IL-1? and Sema3A release; IL-1? was mostly generated by microglia. Intraperitoneal administration of IL-1 receptor antagonists (Kineret, or rytvela [101.10]) decreased these effects and enhanced retinal revascularization; knockdown of Sema3A resulted in microvessel preservation and, conversely, administration of IL-1? caused vaso-obliteration. In vitro, IL-1? derived from activated primary microglial cells, cultured under hyperoxia, stimulated the release of Sema3A in retinal ganglion cells-5, which in turn induced apoptosis of microvascular endothelium; antagonism of IL-1 receptor decreased microglial activation and on retinal ganglion cells-5 abolished the release of Sema3A inhibiting ensuing endothelial cell apoptosis. IL-1? was not directly cytotoxic to endothelial cells.Our findings suggest that in the early stages of O2-induced retinopathy, retinal microglia are activated to produce IL-1?, which sustains the activation of microglia and induces microvascular injury through the release of Sema3A from adjacent neurons. Interference with IL-1 receptor or Sema3A actions preserves the microvascular bed in ischemic retinopathies and, consequently, decreases ensued pathological preretinal neovascularization.

    View details for DOI 10.1161/ATVBAHA.113.301331

    View details for Web of Science ID 000322187600024

    View details for PubMedID 23766263

  • Restoration of renal function by a novel prostaglandin EP4 receptor-derived peptide in models of acute renal failure AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Leduc, M., Hou, X., Hamel, D., Sanchez, M., Quiniou, C., Honore, J., Roy, O., Madaan, A., Lubell, W., Varma, D. R., Mancini, J., Duhamel, F., Peri, K. G., Pichette, V., Heveker, N., Chemtob, S. 2013; 304 (1): R10-R22


    Acute renal failure (ARF) is a serious medical complication characterized by an abrupt and sustained decline in renal function. Despite significant advances in supportive care, there is currently no effective treatment to restore renal function. PGE(2) is a lipid hormone mediator abundantly produced in the kidney, where it acts locally to regulate renal function; several studies suggest that modulating EP(4) receptor activity could improve renal function following kidney injury. An optimized peptidomimetic ligand of EP(4) receptor, THG213.29, was tested for its efficacy to improve renal function (glomerular filtration rate, renal plasma flow, and urine output) and histological changes in a model of ARF induced by either cisplatin or renal artery occlusion in Sprague-Dawley rats. THG213.29 modulated PGE(2)-binding dissociation kinetics, indicative of an allosteric binding mode. Consistently, THG213.29 antagonized EP(4)-mediated relaxation of piglet saphenous vein rings, partially inhibited EP(4)-mediated cAMP production, but did not affect G?(i) activation or ?-arrestin recruitment. In vivo, THG213.29 significantly improved renal function and histological changes in cisplatin- and renal artery occlusion-induced ARF models. THG213.29 increased mRNA expression of heme-oxygenase 1, Bcl2, and FGF-2 in renal cortex; correspondingly, in EP(4)-transfected HEK293 cells, THG213.29 augmented FGF-2 and abrogated EP(4)-dependent overexpression of inflammatory IL-6 and of apoptotic death domain-associated protein and BCL2-associated agonist of cell death. Our results demonstrate that THG213.29 represents a novel class of diuretic agent with noncompetitive allosteric modulator effects on EP(4) receptor, resulting in improved renal function and integrity following acute renal failure.

    View details for DOI 10.1152/ajpregu.00138.2012

    View details for Web of Science ID 000313051200002

    View details for PubMedID 23152113

    View details for PubMedCentralID PMC3543653

  • Toilet technology: Improve sanitation on India's railways. Nature Sharma, A., Unnikrishnan, M. K., Madaan, A. 2012; 489 (7414): 33-?

    View details for DOI 10.1038/489033e

    View details for PubMedID 22955601

  • MEDICATION STORAGE AND SELF MEDICATION PRACTICE AMONG THE YOUTH IN KARNATAKA REGION, INDIA Int J Pharm Sci Res Sharma, A., Madaan, A., Nagappa, A. N. 2012; 3(8) (63): 2795-2800
  • Ghrelin Modulates Physiologic and Pathologic Retinal Angiogenesis through GHSR-1a INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Zaniolo, K., Sapieha, P., Shao, Z., Stahl, A., Zhu, T., Tremblay, S., Picard, E., Madaan, A., Blais, M., Lachapelle, P., Mancini, J., Hardy, P., Smith, L. E., Ong, H., Chemtob, S. 2011; 52 (8): 5376-5386


    Vascular degeneration and the ensuing abnormal vascular proliferation are central to proliferative retinopathies. Given the metabolic discordance associated with these diseases, the authors explored the role of ghrelin and its growth hormone secretagogue receptor 1a (GHSR-1a) in proliferative retinopathy.In a rat model of oxygen-induced retinopathy (OIR), the contribution of ghrelin and GHSR-1a was investigated using the stable ghrelin analogs [Dap3]-ghrelin and GHRP6 and the GSHR-1a antagonists JMV-2959 and [D-Lys3]-GHRP-6. Plasma and retinal levels of ghrelin were analyzed by ELISA, whereas retinal expression and localization of GHSR-1a were examined by immunohistochemistry and Western blot analysis. The angiogenic and vasoprotective properties of ghrelin and its receptor were further confirmed in aortic explants and in models of vaso-obliteration.Ghrelin is produced locally in the retina, whereas GHSR-1a is abundantly expressed in retinal endothelial cells. Ghrelin levels decrease during the vaso-obliterative phase and rise during the proliferative phase of OIR. Intravitreal delivery of [Dap3]-ghrelin during OIR significantly reduces retinal vessel loss when administered during the hyperoxic phase. Conversely, during the neovascular phase, ghrelin promotes pathologic angiogenesis through the activation of GHSR-1a. These angiogenic effects were confirmed ex vivo in aortic explants.New roles were disclosed for the ghrelin-GHSR-1a pathway in the preservation of retinal vasculature during the vaso-obliterative phase of OIR and during the angiogenic phase of OIR. These findings suggest that the ghrelin-GHSR-1a pathway can exert opposing effects on retinal vasculature, depending on the phase of retinopathy, and thus holds therapeutic potential for proliferative retinopathies.

    View details for DOI 10.1167/iovs.10-7152

    View details for Web of Science ID 000293377400048

    View details for PubMedID 21642627

    View details for PubMedCentralID PMC3176063

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