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Futoshi Ishikawa, Hiroshi Ohguro, Ikuyo Ohguro, Hitoshi Yamazaki, Kazuhisa Mamiya, Tomomi Metoki, Tadashi Ito, Yumiko Yokoi, Mitsuru Nakazawa; Prolonged Rhodopsin Phosphorylation in Light-Induced Retinal Degeneration in Rat Models. Invest. Ophthalmol. Vis. Sci. 2006;47(12):5204-5211. doi: 10.1167/iovs.05-1149.
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purpose. The effects of various light-induced stresses on the retina were examined in the retinal degenerative rat model.
methods. Retinal morphology and electroretinograms (ERGs) were analyzed after application of light-induced stress of several intensities (650, 1300, 2500, or 5000 lux). For evaluation of rhodopsin (Rho) function, the kinetics of Rho regeneration and dephosphorylation were studied by spectrophotometric analysis and immunofluorescence labeling with antibodies specifically directed toward the phosphorylated residues 334Ser and 338Ser in the C terminus of Rho. Retinal cGMP concentration was determined by ELISA. Expression levels of neurotrophic factors (FGF2, brain-derived neurotrophic factor [BDNF], platelet-derived growth factor [PDGF], and ciliary neurotrophic factor [CNTF]) were evaluated quantitatively by RT-PCR.
results. Light intensity–dependent deterioration of ERG responses and thinning of the retinal outer nuclear layer were observed in wild-type and Royal College of Surgeons (RCS) rat retinas. Under dark adaptation after light-induced stress, the kinetics of Rho regeneration were not different between wild-type and RCS rat retinas. Rho dephosphorylation at 334Ser and 338Ser was extremely delayed in RCS rat retinas compared with wild-type without light-induced stress, but Rho dephosphorylation at those sites became slower in both RCS and wild-type rat retinas. In terms of expression of neurotrophic factors, almost no significant changes were observed between the animals after light-induced stress.
conclusions. The present study indicates that light-induced stress causes intensity-dependent deterioration in retinal function and morphology in wild-type and RCS rat retinas. Disruption of the phototransduction cascade resulting from slower kinetics of Rho dephosphorylation appears to be involved in retinal degeneration.
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