Indirect Photoreceptor Neuroprotection Through Small Molecule-Induced Growth Factors

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.

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 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 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 of 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. 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.