Misregulation of rhodopsin phosphorylation and dephosphorylation found in P23H rat retinal degeneration

Original Research

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Authors: Yoshiyuki Saito, Hiroshi Ohguro, Ikuyo Ohguro, Noriyuki Sato, Futoshi Ishikawa, et al

Published Date October 2008 Volume 2008:2(4) Pages 821 - 828

DOI: http://dx.doi.org/10.2147/OPTH.S4359

Yoshiyuki Saito¹, Hiroshi Ohguro¹, Ikuyo Ohguro¹, Noriyuki Sato², Futoshi Ishikawa³, Hitoshi Yamazaki³, Tomomi Metoki³, Tadashi Ito³, Mitsuru Nakazawa³

¹Department of Ophthalmology; ²Department of Pathology (Section 1), Sapporo Medical University School of Medicine, Sapporo, Japan; ³Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki, Japan

Abstract: To examine rhodopsin (Rho) functions in P23H rat, kinetics of Rho regeneration and dephosphorylation were investigated by spectrophotometric analysis and immunofluorescence labeling method using specific antibodies toward phosphorylated 334Ser or 338Ser site. Rho dephosphorylation at both sites was extremely delayed in P23H retina as compared to normal ones. Kinetics of Rho regeneration was not altered between normal and P23H rats under dark adaptation. Next, to study the effects of several Ca²⁺ channel blockers on this model, retinal function and morphology were evaluated. Among them, nilvadipine showed a significant protective effect against P23H retinal degeneration. Neurotrophic factor, fibroblast growth factor-2 and Arc, known to suppress the apoptosis in the central nervous system, were significantly upregulated upon administration of nilvadipine. The present study indicates that misregulation of Rho phosphorylation may be involved as an important step in retinal degeneration of P23H and administration of nilvadipine may be a potential therapeutic agent for the retinal degenerations.

Keywords: rhodopsin, P23H rat, retinitis pigmentosa, mutation

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