title: RPGR: Its role in photoreceptor physiology, human disease, and future therapies.
abstract: Mammalian photoreceptors contain specialised connecting cilia that connect the inner (IS) to the outer segments (OS). Dysfunction of the connecting cilia due to mutations in ciliary proteins are a common cause of the inherited retinal dystrophy retinitis pigmentosa (RP). Mutations affecting the Retinitis Pigmentosa GTPase Regulator (RPGR) protein is one such cause, affecting 10-20% of all people with RP and the majority of those with X-linked RP. RPGR is located in photoreceptor connecting cilia. It interacts with a wide variety of ciliary proteins, but its exact function is unknown. Recently, there have been important advances both in our understanding of RPGR function and towards the development of a therapy. This review summarises the existing literature on human RPGR function and dysfunction, and suggests that RPGR plays a role in the function of the ciliary gate, which controls access of both membrane and soluble proteins to the photoreceptor outer segment. We discuss key models used to investigate and treat RPGR disease and suggest that gene augmentation therapy offers a realistic therapeutic approach, although important questions still remain to be answered, while cell replacement therapy based on retinal progenitor cells represents a more distant prospect.
authors.affiliation: Scottish Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, United Kingdom. Electronic address: rolymegaw@ed.ac.uk.
authors.forename: Roly D
authors.initials: RD
authors.lastname: Megaw
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom. Electronic address: Dinesh.Soares@ed.ac.uk.
authors.forename: Dinesh C
authors.initials: DC
authors.lastname: Soares
authors.affiliation: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom. Electronic address: alan.wright@igmm.ed.ac.uk.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000502:physiology*; D015316:Genetic Therapy; D006801:Humans; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D055212:Photoreceptor Connecting Cilium / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D005136:Eye Proteins; C099929:RPGR protein, human
keywords: Animal model; Ciliopathy; Gene therapy; Human disease; RPGR; Retinitis pigmentosa; Stem cell