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