Retinitis Pigmentosa: Genes and Disease Mechanisms

TLDR

Retinitis pigmentosa is an inherited retinal disorder affecting 1 in 3,000–7,000 people, caused by photoreceptor or retinal pigment epithelium abnormalities, and is genetically heterogeneous with over 40 associated genes. This review aims to catalogue the genes implicated in RP and to outline how their mutations drive retinal degeneration, while highlighting future prospects for genotype‑phenotype correlation to inform disease risk and therapeutic choices. The authors synthesize current knowledge on the pathogenic mechanisms by which mutations in RP genes disrupt photoreceptor or RPE function, leading to progressive retinal degeneration.

Abstract

Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000-7000 people and characterized by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina which lead to progressive visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. While usually limited to the eye, RP may also occur as part of a syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have been associated with RP so far, with the majority of them expressed in either the photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of the disease makes the genetics of RP complicated, thus rendering genotype-phenotype correlations not fully applicable yet. In addition to the multiplicity of mutations, in fact, different mutations in the same gene may cause different diseases. We will here review which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration. In the future, a more thorough analysis of genetic and clinical data together with a better understanding of the genotype-phenotype correlation might allow to reveal important information with respect to the likelihood of disease development and choices of therapy.