ABSTRACT
In a review of retinitis pigmentosa (RP) written in 1976 (1), Merin and Auerbach mentioned that, in spite of voluminous literature on the subject, many questions about RP remained unanswered. In spite of extensive basic and clinical research, studies of experimentally induced and pathologic specimens of RP, symposia, books and thousands of articles devoted to RP, they remained so through the end of the 1980s (2). The breakthrough came with the advent of molecular genetics, and later, the detection of more and more genes associated with RP-causing mutations. The advance in the understanding of RP-related molecular genetics enabled a better understanding of the pathophysiology, biochemistry, electrophysiology, and clinical classifications of these diseases. In 1992, Humphries et al. marked the identification of two genes associated with RP (3). The discovery that both these genes encode transmembrane proteins of the rod outer segments indicated the important link between genetics, physiology and pathophysiology. In fact, in 1996 when 20 loci for RP were identified with seven genes cloned, Berson (4) considered the understanding of the effect of the mutation on the pathophysiology the most important contribution of the new developments in genetics. By the year 2000, 55 genes had been identified and 118 loci associated with photoreceptor degenerative diseases were known (5). By April 2004, the number of such known genes increased to 70, plus four mutations of the mitochondrial DNA (6). We are now not far from the point of recognizing all genes associated with RP. The 1990s marked the advent of a better understanding of mechanisms of normal function of photoreceptors (7) and of programmed cell death (apoptosis), a major factor in RP (8).
