Genetics of Retinal Disease

Abstract

Abstract The retina forms the inner lining of the posterior segment of the eye. Vision is dependent on intact retinal photoreceptors to transduce incident light to an electrical signal for relay to the brain. The function of these cells is in turn reliant upon their intimate relationship with the adjacent retinal pigment epithelium (RPE). Indeed, if RPE cells become degenerate or are lost, PR degeneration ensues and vice versa . These events form the basis of vision loss in many retinal degenerative diseases and are key features of such conditions as age‐related macular degeneration (AMD), retinitis pigmentosa and other genetically inherited retinal diseases such as Stargardt macular dystrophy. Cumulatively, these conditions now comprise the foremost causes of untreatable visual loss in developed countries. The diverse phenotypes observed reflect the remarkable genetic heterogeneity of retinal disease. Furthermore, different mutations within the same gene can cause different phenotypes. AMD is now known to be a complex genetic disorder with a number of genetic variants (single nucleotide polymorphisms, SNPs) now known to confer susceptibility to vision loss from the condition. Key Concepts: The retina is a multilayered neural tissue that comprises a variety of highly specialised cells that receive and process visual stimuli. The majority of genetic diseases of the retina affect the photoreceptor cell. Although many diseases affect the whole retina, certain conditions affect predominantly or exclusively the macula of the eye, that region of the retina specialised for central vision. More than 200 genes have been identified that cause monogenic retinal degeneration in humans. Hundreds of mutations have been described that can be inherited as autosomal dominant, recessive, X‐linked, mitochondrial, oligogenic and digenic traits. Monogenic retinal diseases are slowly progressive and in many instances lead to blindness. Age‐related macular degeneration is the most frequent cause of blindness in older individuals. It is a complex disease, one that arises due to the interplay of both multiple genetic and environmental factors. Although major advances are being made in treating these with gene and stem cell therapies, there is no currently approved treatment.