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The Biomarker Initiative

Retinal ganglion cell image from the Huberman lab
Retinal ganglion cell image from the Huberman lab

The Catalyst for a Cure Biomarker Initiative funded by Glaucoma Research Foundation is a collaborative research effort designed to accelerate the pace of discovery toward better treatments and ultimately a cure for glaucoma.

The Catalyst for a Cure (CFC) principal investigators are: Alfredo Dubra, PhD, Medical College of Wisconsin; Jeffrey Goldberg, MD, PhD, Shiley Eye Center, University of California San Diego; Andrew Huberman, PhD, University of California San Diego; and Vivek Srinivasan, PhD, University of California Davis. This report from the CFC researchers summarizes findings as of February 2014.

New Biomarker Targets

Glaucoma is a leading cause of blindness worldwide. A major obstacle in the treatment and prevention of vision loss is the inability to detect the disease early, or to know which patients are at greater risk of losing vision. During the first 2 years of the collaboration, the Catalyst for a Cure team has identified several possible glaucoma biomarkers. In addition they have built a series of novel instruments for imaging the retina non-invasively that will be used to measure and test these new biomarkers.

The consortium of 4 research labs is highly collaborative, combining expertise in state of the art imaging, cellular and molecular biology, and clinical glaucoma. They are applying their expertise toward biomarker discovery with the direct goal of improving patient care.

Major Areas of Progress

  • The team identified a subset of retinal ganglion cells (RGCs) that are among the earliest to show changes in glaucoma. This discovery has generated an exciting new approach, with a goal to design specific vision tests for identifying early glaucoma in patients who are more likely to lose vision if left untreated.
  • The degeneration of the connections, or "synapses," between retinal ganglion cells and neighboring cells is an early event in glaucoma. The team is developing probes for synaptic labeling and imaging technology to see synapses in the eye, to be perfected in models of glaucoma and in humans.
  • The smallest retinal blood vessels are intimately involved with retinal ganglion cells in the retina and optic nerve. The CFC team developed a number of novel approaches to visualize this microvasculature non-invasively, measure local blood flow and oxygenation, and even developed new probes that could be given as a simple blood test to determine whether retinal neurons or axons going into the optic nerve are dysfunctional or at risk.
  • The energy sources of the cell (mitochondria) are dysfunctional in both form and function in glaucoma models. The CFC has made significant progress in using non-invasive imaging modalities to detect fluorescently labeled mitochondria and has characterized the relationship between retinal ganglion cell mitochondria and activity in normal versus glaucomatous eyes.
  • The CFC has made considerable advances in developing non-invasive retinal imaging instruments including adaptive optics-scanning laser ophthalmoscopes; visible light, path-length-resolved spectroscopy; and infrared optical coherence tomography angiography.

Translating for Clinical Use

Together, one or more of these approaches may yield highly sensitive biomarkers for glaucoma detection and progression, and provide a sensitive means to monitor treatment efficacy. The Catalyst for a Cure team continues to work towards validation of these targets and technologies in models of glaucoma, and towards rapid translation into human testing.

Last reviewed on March 22, 2017

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