Astrocytes Regulate the Health and Degeneration of Retinal Ganglion Cells in Glaucoma Neurodegeneration

Astrocytes are known to play vital roles in the maintenance of retinal ganglion cells, with these interactions adversely affected in glaucoma. In particular, as is common across a number of neurodegenerative diseases, the mitochondria of these cells are damaged, presumably leading to the disease phenotypes. The use of human pluripotent stem cells allows for the precise modeling of these interactions in a dish, providing the spatial and temporal resolution to closely examine how mitochondrial function is changed in these cells as a result of glaucoma, as well as how these changes in mitochondria alter the health and function of the cells as a whole.

The goal of this project is to examine the ways in which astrocytes, a type of support cell found throughout the central nervous system, can be adversely affected in glaucoma, leading to the degeneration of retinal ganglion cells. To accomplish this, we will utilize an in vitro human pluripotent stem cell model of glaucoma derived from samples from patients with inherited forms of the disease, as well as unaffected control cell lines. These cells will be differentiated into both retinal ganglion cells and astrocytes, and these differentiated cells will be grown together to examine the ways in which astrocytes regulate retinal ganglion cell function and viability. Through the use of these stem cell models, we are able to analyze mechanisms underlying the disease state in astrocytes and retinal ganglion cells in a human cellular model. Once the study is complete, we hope that results will illustrate the importance of astrocytes in the disease state, providing new pathways for the development of therapeutic approaches to glaucoma.