Retinitis pigmentosa: Defined from a molecular point of view

Retinitis pigmentosa (RP) denotes a group of hereditary retinal dystrophies , characterized by the early onset of night blindness followed by a progres sive loss of the visual field. The primary defect underlying RP affects the function of the rod photoreceptor cell, and, subsequently, mostly unknown molecular and cellular mechanisms trigger the apoptotic degeneration of the se photoreceptor cells. Retinitis pigmentosa is very heterogeneous, both ph enotypically and genetically. In this review Mle propose a tentative classi fication of RP based on the functional systems affected by the mutated prot eins. This classification connects the variety of phenotypes to the mutatio ns and segregation patterns observed in RT. Current progress in the identif ication of the molecular defects underlying RP reveals that at least three distinct functional mechanisms may be affected: 1) the daily renewal and sh edding of the photoreceptor outer segments, 2) the visual transduction casc ade, and 3) the retinol (vitamin A) metabolism. The first group includes th e rhodopsin and peripherin/RDS genes, and mutations in these genes often re sult in a dominant phenotype. The second group is predominantly associated with a recessive phenotype that results, as we argue, from continuous inact ivation of the transduction pathway. Disturbances in the retinal metabolism seem to be associated with equal rod and cone involvement and the presence of deposits in the retinal pigment epithelium. (C) 1999 by Elsevier Scienc e Inc. All rights reserved.