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We have been interested in cellular regulatory mechanisms operating in mammalian retinal neurons, especially those determining sensitivity to factors which either promote or inhibit cell death. The production of reactive oxygen species through oxidative stress is believed to be an important mediator of neuronal cell death although the precise mechanism by which this occurs is unknown. Pigment epithelia derived factor (PEDF) has been shown to promotes neurotrophic differentiation and the survival of neurons of the central nervous system. Using a cell culture system, we demonstrate that multiple populations of retinal neurons can differentiate and be maintained in a chemically defined environment and that cell death induced by reactive oxygen species can be quantitated. The data also show that this induced death is dose dependent and occurs by an apoptotic mechanism which can be inhibited by PEDF. The mechanism by which PEDF provides this protection may be very important for inhibiting the apoptotic death of retinal neurons which occurs in retinitis pigmentosa, macular degeneration, glaucoma or other neurodegenerative diseases. These cultured neurons will also be useful for analyzing apoptotic responses of each of the retinal neuron cell types to a variety of "cytotoxic" agents and to the rescue effect of a number of "factors" either alone or in combination. [ABSTRACT FROM AUTHOR]