From the Research
Etiology of Retinitis Pigmentosa
The etiology of retinitis pigmentosa (RP) is complex and involves multiple genetic and molecular mechanisms.
- RP is a group of inherited disorders affecting the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina, leading to progressive visual loss 1, 2.
- The disease can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner, and is associated with over 40 genes, most of which are expressed in the photoreceptors or retinal pigment epithelium 1.
- The pathogenesis of RP is still unclear, but evidence suggests that vascular dysfunction and microglia activation may play a role in the progression of the disease 3.
- RP can occur in isolation (nonsyndromic) or as part of a genetic, metabolic, or neurologic syndrome or disorder, such as Usher syndrome and Bardet-Biedl syndrome 1, 2, 4.
Genetic Mechanisms
- The genetics of RP are complicated, with multiple mutations in different genes leading to the disease, and different mutations in the same gene causing different diseases 1.
- Over 45 causative genes/loci have been identified in non-syndromic RP, and molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease 2.
- Recent studies have shown promising progress in elucidating the photoreceptor degeneration mechanism, and the discovery of novel molecule therapeutics that can selectively target specific receptors or pathways may serve as a foundation for advanced drug development 5.
Molecular Pathways
- The development of RP involves alterations in molecular pathways, including endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability 5.
- Therapeutic approaches under development include gene and cell therapy, and the identification of novel potential drug targets for RP 5.