Retinitis Pigmentosa: Over-expression of anti-ageing protein Klotho in degenerating photoreceptors.
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Retinitis Pigmentosa involves a hereditary degeneration of photoreceptors by as yet unresolved mechanisms. The secretable protein α-Klotho has a function related to ageing processes, and α-Klotho deficient mice have reduced lifespan and declining functions in several tissues. Here, we studied Klotho in connection with inherited photoreceptor degeneration. Increased nuclear immunostaining for α-Klotho protein was seen in degenerating photoreceptors in four different Retinitis Pigmentosa models (rd1, rd2 mice; P23H, S334ter rhodopsin mutant rats). Correspondingly, in rd1 retina α-Klotho mRNA expression was significantly upregulated. Moreover, immunostaining for another Klotho family protein, β-Klotho, also co-localised with degenerating rd1 photoreceptors. The rd1 retina displayed reduced levels of fibroblast growth factor (FGF) 15, a member of the FGF subfamily for which Klotho acts as a co-receptor. Exogenous α-Klotho protein added to retinal explant cultures did not affect cell death in rd1 retinae, but caused a severe layer disordering in wild-type retinae. Our work suggests Klotho as a novel player in the retina, with a clear connection to photoreceptor cell death as well as with an influence on retinal organization. This article is protected by copyright. All rights reserved.