title: Prolonged rhodopsin phosphorylation in light-induced retinal degeneration in rat models.
abstract: OBJECTIVE
  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 (334)Ser and (338)Ser 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 (334)Ser and (338)Ser 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.
authors.affiliation: Department of Ophthalmology, Hirosaki University School of Medicine, Hirosaki, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohguro
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ohguro
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Mamiya
authors.forename: Tomomi
authors.initials: T
authors.lastname: Metoki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ito
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yokoi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D003623:Dark Adaptation; D004596:Electroretinography / Q000528:radiation effects; D004797:Enzyme-Linked Immunosorbent Assay; D008027:Light; D008856:Microscopy, Fluorescence; D009414:Nerve Growth Factors / Q000235:genetics; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D012160:Retina / Q000378:metabolism / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000378:metabolism*
chemical_list: D009414:Nerve Growth Factors; D012333:RNA, Messenger; D012243:Rhodopsin; D006152:Cyclic GMP