Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy.
Retinitis pigmentosa (RP) is a group of retinal degenerative diseases that are characterised primarily by the loss of rod photoreceptor cells. Mutations in rhodopsin are the most common cause of autosomal-dominant RP (ADRP). Here, we propose a new classification for rhodopsin mutations based on their biochemical and cellular properties. Several different potential gain-of-function mechanisms for rhodopsin ADRP are described and discussed. Possible dominant-negative mechanisms, which affect the processing, translocation or degradation of wild-type rhodopsin, are also considered. Understanding the molecular and cellular consequences of rod-opsin mutations and the underlying disease mechanisms in ADRP are essential to develop future therapies for this class of retinal dystrophies.
Mendes
Hugo F
HF
Division of Pathology, Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
van der Spuy
Jacqueline
J
Chapple
J Paul
JP
Cheetham
Michael E
ME
D000595:Amino Acid Sequence; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics*
D012243:Rhodopsin