> Creating a field of molecular surgery to guide new therapies
Creating a field of molecular surgery to guide new therapies
A significant challenge for ophthalmologists is diagnosing diseases that appear clinically similar. Inside the eye, a “snowstorm” of white cells can be due to an autoimmune disease, cancer, or an infection, each requiring very different therapies. Current hospital laboratory testing is slow, and results can be inconclusive. Vinit Mahajan, MD, PhD,associate professor of ophthalmology, believes new molecular technologies in precision health will overcome these challenges.
After conventional therapies failed a family of patients going blind from severe inflammation, Mahajan and his research team surveyed their eye fluid and found unexpected protein signatures responsible for the inflammation, bleeding, and scar tissue formation. The team was able to select the right drugs—typically not used for eye diseases—to target the abnormal proteins and restore sight. At the same time, they were able to avoid some drugs most doctors were prescribing, because they knew their target proteins were absent in the diseased eyes.
“Analyzing fluid samples from the eye can completely change how we treat patients,” Mahajan said.
Mahajan and his research team are experts in characterizing proteins from liquid eye biopsies using proteomics technology. In only a few drops of fluid, they can measure thousands of molecules to identify overabundant proteins that trigger vision loss. Those proteins can then be matched with on-the-market drugs.
The success of this molecular approach demonstrates the potential of treating rare and complex eye conditions by matching drugs with individual disease proteins. With this in mind, Mahajan established the Molecular Surgery Program at Stanford’s Byers Eye Institute. This program now supports the collection and analysis of eye fluid from patients with macular degeneration, glaucoma, corneal transplants, infections, and cancer.
“If we can identify the molecules linked to eye disease, we can make precise diagnoses, choose the right medicines, and improve our surgical outcomes,” Mahajan said.
Using new proteomics technologies, Mahajan’s team can quickly find specific protein expression signatures that distinguish each of these conditions. Getting the correct diagnosis as soon as possible is essential to choosing the right therapy approach, and these protein biomarkers can provide the needed clarity.
Fluid analysis has also pointed to novel retinal disease proteins that do not yet have a drug therapy. Mahajan’s team is exploring these new disease proteins at the atomic level and working with colleagues in Stanford’s Chemistry and Structural Biology programs to design innovative small-molecule drugs.
“We can now think beyond using surgery as a means of manipulating tissues,” Mahajan said. “Manipulating molecules through surgery is the next step in highly personalized, precision medicine.”
Once surgeons and scientists have a molecular target in their sights, numerous molecular drugs are available to them. These may involve enzymes, genes, antibodies, or chemicals. Eye surgeons can precisely and safely deliver any of these molecules near specific cells in the eye, avoiding the toxicity and issues associated with drugs taken by mouth or injected into the blood stream. Once delivered, patients can be observed noninvasively in the clinic using ultra-high-resolution cameras.
“Recasting eye surgery in molecular terms will allow Stanford ophthalmologists to take innovative approaches to curing blindness,” Mahajan said.
By MARYANN MAHAJAN
MaryAnn joined Mahajan's lab in 2008. She earned her B.A. in English at the University of California, Berkeley and attended graduate school at the University of California, Los Angeles where she earned a secondary teaching credential. She is a writer and editor and also performs histological phenotyping of mouse eyes.