A New Approach to Rescuing Photoreceptors from Death through Activation of Endogenous Neuroprotective Mechanisms

Petr Baranov, MD, PhD
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary (Harvard) (Boston, MA)
Year Awarded:
2016
Grant Duration:
July 1, 2016 to June 30, 2018
Disease:
Macular Degeneration
Award Amount:
$159,641
Grant Reference ID:
M2016046
Award Type:
Standard
Award Region:
US Northeastern
Petr Baranov, MD, PhD

Indirect Photoreceptor Neuroprotection through Small Molecule-Induced Growth Factors

Summary

We aim to identify small molecules that can induce endogenous growth factors in the sensory part of the eye, the retina. Our overall goal is to investigate the power that this indirect neuroprotection might have to rescue photoreceptors and ganglion cells from death, overcoming limitations usually associated with growth factor delivery. The results of our studies should lead to the development of novel, accessible and effective molecular therapies for retinal degeneration and other neurodegenerative disorders.

Details

Our laboratory is looking for chemicals that can trigger the production of endogenous growth factors in the sensory part of the eye known as the retina. This indirect neuroprotection approach is of a particular interest for widespread diseases of complex origin, such as age-related macular degeneration (AMD).

To identify proper targets for such a therapy, we combine the advances in automated microscopy with the methods of stem cell biology and genetic engineering. First, induced pluripotent stem cells are genetically modified to carry a reporter gene, which provides a signal, ie, the cell itself will change its fluorescence if a particular growth factor is produced. Then, these stem cells are expanded and trillions of cells are differentiated into retinal tissue, followed by treatment with thousands of chemicals. The identified “hit” molecules are then tested for their ability to prevent photoreceptor death in an established animal models of retinal degeneration. We have an ability to non-invasively study retinal structure and response to light using optical coherence tomography and electroretinography.

This approach, of using multichannel automated imaging in vitro, allows to study the induction of several growth factors simultaneously in a high throughput manner. And the use of stem cells minimizes the number of animals needed for pre-clinical work.

The support from the BrightFocus Foundation we plan to identify novel targets for neuron rescue. And we believe that the exploration of this indirect neuroprotective strategy should lead to the development of novel, accessible and effective molecular therapies for macular degeneration and other neurodegenerative disorders.

About the Researcher

After completing medical school and graduate school at Russian State Medical University (Moscow) in 2011, I joined the lab of Michael Young at Schepens Eye Research Institute in Boston for a postdoctoral fellowship. During those years I was fortunate to participate in the pre-clinical development of stem cell based therapy for retinal degeneration. Since 2015, as an investigator, I have pursued several independent research projects with a major interest in retinal neuroprotection with growth factors and small molecules.

Personal Story

As a child I was amazed by the complexity of vision. Growing up in computer era, it is hard to believe that one organ can process that much information in a snap. Unfortunately, the cells in the retina, responsible for the acquisition and processing of this information, do not renew during our life. That’s why I am dedicated to the search of therapeutics that could protect gentle photoreceptors from stress.

I am extremely grateful to BrightFocus Foundation and its donors, who made it possible for me to pursue a research career in the United States.  I am dedicated to the discovery of the therapies for macular degeneration, and truly believe that I will witness blindness’ defeat in my lifetime.

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