Growth Factors and Retinal Ganglion Cell Survival

It is estimated that more than two million Americans have been diagnosed with glaucoma and that it is among the most common causes of blindness in the United States. At the current time, the decision to initiate treatment of glaucoma depends largely on recognizing the characteristic structural changes in the optic nerve head and/or loss of visual field. Although elevated intraocular pressure is a leading risk factor, as many as one third of eyes are considered to be within normal limits for intraocular pressure when first diagnosed. By the time reduction of visual performance in a standard visual field test is recognized, retinal ganglion cell loss may already be substantial. These ganglion cells convey visual information from the eye to the brain. Loss of these cells correlates with blindness in glaucoma. Recently new methods such as color visual field analysis are proving: 1) to show progressive loss sooner than conventional field analysis in eyes with glaucoma; 2) to show deficits in suspect eyes when conventional visual fields are normal; and 3) to identify early functional loss in eyes at greatest risk for primary open angle glaucoma. Thus, a retinal ganglion cell supporting treatment might prove useful to stabilize jeopardized retinal ganglion cells in patients with suspected or early stage glaucoma. Recently we have developed a cell culture system in which ganglion cells from newborn rats. Using this system, we have found that rat ganglion cell survival: 1) is dependent upon the availability of certain steroid hormones, 2) can be enhanced by nerve growth factor, epidermal growth factor, and transforming growth factor alpha and 3) is enhanced when epidermal growth factor is combined with insulin. In the present project, we will extend these initial findings by examining several additional growth factors as well as investigate the possibility that several factors together may promote greater survival than any one factor alone. We will also use antibodies to investigate the possibility that these treatments may induce the cultured ganglion cells to grow special features that are unique to ganglion cells in the eye. Knowledge of the specific retinal ganglion cell survival requirements will help in design of a treatment based on growth factors that effectively promotes survival of retinal ganglion cells and yet has minimal side effects.