Retinitis Pigmentosa: Genes and Disease Mechanisms

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.

Protective effect of sulforaphane against retinal degeneration in the Pde6rd10 mouse model of retinitis pigmentosa

“…(5) However, the effective treatments targeting these genetic defects have yet to be reported. Pde6b (cGMP phosphodiesterase 6B, rod receptor, beta polypeptide) encodes the beta subunit of phosphodiesterase (PDE), a peripheral membrane enzyme involved in the phototransduction cascade in rod photoreceptors.…”

“…(6,7) This mutation also causes human autosomal recessive RP. (5,8) Progressive retinal outer nuclear layer (ONL) degeneration in rd10 mouse was observed around post-natal day 16 (P16), followed by a progressive reduction in visual function, determined by measuring rod and cone ERG a-wave and b-wave. Compared with rd1 , the rd10 phenotype has a slower onset and milder retinal degeneration and may provide a better model of RP for testing drug therapy.…”

A Cost-Effective Mutation Screening Strategy for Inherited Retinal Dystrophies

“…Three out of the 76 patients were diagnosed with Bardet-Biedl syndrome (BBS), according to clinical criteria, i.e. rod-cone dystrophy (>90%), truncal obesity (72%), postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism, complex female genitourinary malformations, and renal abnormalities [4]. Two of the samples from BBS patients have recently been genetically characterized using a high-resolution melting analysis approach, and therefore were included as positive controls [22].…”

“…Most cases are monogenic, such as in retinitis pigmentosa (RP), the most common form of IRD, or cone-rod dystrophy, with about 100 associated genes so far identified (Retnet: http://www.sph.uth.tmc.edu/Retnet/). The high number of genes and variants involved and other factors, such as noncanonical Mendelian inheritance patterns or variations of the fraction of disease-causing mutations associated with ethnicity and geography, have made the molecular characterization of genetic retinal dystrophies a real challenge [4,5]. …”

Screening for mutations in RPGR and RP2 genes in Jordanian families with X-linked retinitis pigmentosa

“…Rare forms, such as X-linked dominant, mitochondrial, and digenic RP also exist. X-linked RP (XLRP) accounts for 10 to 15% of all cases (Ferrari et al, 2011), and represents the most severe inherited form in terms of early onset and rapid progression of retinal degeneration in men (Aldred et al, 1994;García-Hoyos et al, 2006). According to a recent report by Shifera and Kay (2015), female carriers of XLRP may also manifest an early-onset, severe form of the disease, although the reason for this remains unclear.…”