The Role of Dominant Rhodopsin Mutations in Drosophila Retinal Degeneration
Mutations within the human rod opsin gene are responsible for approximately 25% of the autosomal dominant forms of retinitis pigmentosa (ADRP) afflicting human populations (l).There are over 60 different mutations known in the rhodopsin gene that cause ADRP. To account for the mechanisms by which these mutations can cause retinal degeneration, three general types of models have been considered. First, improper folding mutant protein may prevent its proper maturation (2). A second model is that the mutated forms may produce rhodopsins that are constitutively active, leading to increased metabolic activity (3). A third possibility is that the mutant proteins show improper cellular localization (4). All three views are consistent with a scenario by which the dominant rhodopsin mutation reduces the health of the photoreceptor, eventually causing the cell to degenerate. Understanding the molecular basis of rhodopsin-based forms of ADRP represents a major advance, but it is likely that successful strategies for alleviating the disease will require additional knowledge on the mechanisms by which these rhodopsin mutants trigger retinal degeneration.
KeywordsRetinitis Pigmentosa Photoreceptor Cell Endoplasmic Reticulum Membrane Retinal Degeneration Photoreceptor Degeneration
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