- Ross A. Poché, Ph.D. Neuronal degeneration lies at the heart of a spectrum of debilitating human cognitive and motor diseases including Alzheimer’s and Parkinson’s disease as well as sensory diseases such as blindness. By characterizing cell populations within the retina, which have the ability to generate new neurons, therapeutic approaches could be employed to harness the ability of these cells to cure human neurological diseases. The objective of my research is to determine the potential of the mammalian retina for repair via endogenous mechanisms. In response to retinal damage, Müller glial (MG) cells of several vertebrate model systems have been shown to give rise to new retinal neurons. However, in mammals, there is a paucity of data directly testing the regenerative capacity of MG cells in vivo. My central hypothesis is that, in response to retinal damage, mature mouse MG cells possess the ability to re-enter the cell cycle and trans-differentiate into retinal neurons. The overall goal of my research is to test this hypothesis by performing genetic, Cre-loxP fate mapping experiments and time lapse imaging of retinal explants. I also aim to characterize the molecular pathways which confer stem cell-like ability upon the MG cells. Preliminary data suggests that the transcription factor, Sox9 may function in such a manner.
Another area of interest is characterization of the damaged retinal environment as it relates to neovascularization. Data from patients and animal models have suggested that early events of diabetic retinopathy show a very tight correlation with the appearance of reactive MG cells and subsequent neo-vascularization. However, this relationship is not well understood. Also, mice which undergo constitutive reactive gliosis or suffering from acute retinal damage exhibit significant increases in vessel branching and size. By rigorously characterizing the vascular structure of damaged retinae derived from various genetic contexts, I will gain insight into primary affected vascular cell types and subsequent overall vascular changes. With such data, I will be in a position to develop new hypotheses on the vasculature’s role during retinal repair to test in future studies.