Grant: Project Grant

The retina is a neural layer at the back of the eye that is responsible for visual processing. Photoreceptors, which line the back of the retina, are light-sensitive neurons that capture visual information and transmit it to the brain so that we can see. For the retina to function properly, the correct numbers of photoreceptors must be generated during development, and these photosensitive neurons must survive into adulthood. If photoreceptors die, light information cannot be processed and vision is lost. It is currently not feasible to replace lost photoreceptors, so visual loss or blindness is permanent. However, in fish and frogs, photoreceptors can regenerate through the latent stem cell properties of a group of retinal cells called Müller glia. Why Müller glia have lost stem cell properties in mammals is beginning to be elucidated and rekindling this stem cell behavior may allow regeneration to occur. We identified a gene known as Pten that regulates both photoreceptor differentiation and degeneration and Muller glia activation. We hypothesize that by studying Pten, we will be better positioned to develop regenerative strategies that promote photoreceptor survival and regeneration. This grant will focus on understanding how Pten and its downstream effectors regulate Müller glia activation (aim 1), photoreceptor differentiation (aim 2) and photoreceptor degeneration (aim 3). We are well positioned to conduct these studies as we have a successful track record of studying retinal biology. Further investigation of Pten functions in the retina will facilitate our design of reparative strategies for vision loss. Our studies may also be applicable to other regions of the central nervous system, such as the brain and spinal cord, where Pten may similarly maintain prevent regeneration after injury or disease.