Ganglion Cell Gene Expression

The vertebrate retina is composed of several layers of different cell types, which act collectively in processing and transmitting a light stimulus to the brain. The innermost layer of cells, the ganglion nerve cells, comprise the final step in this phenomenon. They send processes directly to the brain from the retina via the optic nerve. Virtually no scientific research has been carried out on what the genetic controls are that govern the growth and function of ganglion cells. We propose to initiate an investigation of the molecular gene products that are expressed in the ganglion cells as a first step in determining the genetic controls in these cells. As it is the expression of specific genes that ultimately define the structure and function of a cell, we will concentrate this investigation to genes that are only expressed in ganglion cells. The study of ganglion cell gene expression will not only produce valuable information on the mechanisms controlling structure and function of these cells, but will also allow us to examine the molecular events that lead up to ganglion cell death as a result of glaucoma. Glaucoma is a disease that affects 2% of the population over 40. It is characterized by an increase in the fluid pressure within the eyeball (although in some forms of glaucoma this pressure does not occur) and ultimately leads to blindness because of the selective death of ganglion cells. Curiously, no other cell type in the retina is affected by this disease. In addition, in the early stages of glaucoma, only a select subpopulation of ganglion cells are affected, while other ganglion cells appear to be more resistant. The genetic basis for this selective atrophy of ganglion cells is not known. In addition to examining the gene expression in ganglion cells in eyes with glaucoma, we will also analyze the expression of genes directly associated with the disease. Such gene expression may not be restricted to ganglion cells, but may be exhibited by other cell types of the retina. For example, one possibility is that certain gene products expressed by non-ganglion cells may confer a protective measure to these cells. Hence, we are proposing a two-fold analysis of the molecular biology of glaucoma. On one hand, we will investigate gene expression in the subpopulation of ganglion cells that are most adversely affected by the disease, while on the other hand we will carry out a broader survey of the retina for gene expression that is directly altered by glaucoma.