How to keep photoreceptors alive

Abstract

Over the last 40 years, there has been increasing success in the surgical treatment of retinal detachment in that the retinal reattachment could be achieved in a high proportion of cases but visual recovery was frequently poor. An explanation for this poor visual outcome was derived from work on experimental retinal detachment in which it was shown that photoreceptor cell death occurred because of a wave of apoptosis during the first few days of retinal detachment (1). It is recognized that apoptosis or programmed cell death is a genetically encoded potential of all cells (2). It is characterized by cleavage of most of the nuclear DNA into short but well organized chains of nucleosomes in multiples of 200 bp by an endogenous nonlysosomal nuclease (3, 4) and may be triggered by changes in the metabolic environment of the cell. The photoreceptor cells are closely approximated to the retinal pigment epithelium (Fig. 1) and depend on the retinal pigment epithelium for their metabolic sustenance. Physical separation of the two and loss of metabolic exchange as occurs in retinal detachment (Fig. 2) might have been supposed to cause a sequence of events that would inevitably induce cell loss that was not amenable to treatment. However, apoptosis may be manipulated by altering the metabolic environment, and it has been shown that brain-derived growth factor injected into the eye reduces the rate of photoreceptor cell loss in experimental retinal detachment (5), although the precise means by which apoptosis was induced and the mechanism of the therapeutic effect were uncertain.