title: Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching.
abstract: OBJECTIVE
  Acute white-light damage to rods depends on the amount of rhodopsin available for bleaching during light exposure. Bleached rhodopsin is metabolically regenerated through the visual cycle involving the pigment epithelium, or photochemically by deep blue light through photoreversal of bleaching. Because photoreversal is faster than metabolic regeneration of rhodopsin by several orders of magnitude, the photon catch capacity of the retina is significantly augmented during blue-light illumination, which may explain the greater susceptibility of the retina to blue light than to green light. However, blue light can also affect function of several blue-light-absorbing enzymes that may lead to the induction of retinal damage. Therefore, this study was conducted to test whether rhodopsin and its bleaching intermediates play a role in blue-light-induced retinal degeneration.
  
  
  METHODS
  Eyes of anesthetized rats and mice that did or did not contain rhodopsin were exposed to green (550 +/- 10 nm) or deep blue (403 +/- 10 nm) light for up to 2 hours. Rats with nearly rhodopsinless retinas were obtained by bleaching rhodopsin in animals with inhibited metabolic rhodopsin regeneration-that is, under halothane anesthesia. In addition, Rpe65(-/-) mice that are completely without rhodopsin were used to test the susceptibility to blue-light damage of a rodent retina completely devoid of the visual pigment. Effects of illumination on photoreceptor morphology were assessed 24 hours or 10 days thereafter by morphologic and biochemical methods.
  
  
  RESULTS
  Exposure to blue light resulted in severe retinal damage and activation of the transcription factor AP-1 in rats. In contrast, green light had no effect. When rhodopsin was almost completely bleached by short-term green-light exposure while metabolic regeneration (but not photoreversal) was prevented by halothane anesthesia, blue-light exposure induced distinct lesions in rat retinas. When both metabolic rhodopsin regeneration and photoreversal of bleaching were almost completely inhibited, blue-light exposure caused only very moderate lesions. When mice without rhodopsin were exposed to blue light, no damage occurred, in contrast to wild-type control mice.
  
  
  CONCLUSIONS
  Short time exposure to blue light has deleterious effects on retinal morphology. Because damage was observed only in the presence of the visual pigment, blue-light-induced retinal degeneration is rhodopsin mediated. Absorption of blue light by other proteins is not sufficient to induce light damage. Photoreversal of bleaching, which occurs only in blue but not in green light, increases the photon-catch capacity of the retina and may thus account for the difference in the damage potential between blue and green light.
authors.affiliation: Department of Ophthalmology, University Eye Clinic, Zurich, Switzerland. cgrimm@opht.unizh.ch
authors.forename: C
authors.initials: C
authors.lastname: Grimm
authors.forename: A
authors.initials: A
authors.lastname: Wenzel
authors.forename: T
authors.initials: T
authors.lastname: Williams
authors.forename: P
authors.initials: P
authors.lastname: Rol
authors.forename: F
authors.initials: F
authors.lastname: Hafezi
authors.forename: C
authors.initials: C
authors.lastname: Remé
mesh_terms: D000818:Animals; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D018808:Transcription Factor AP-1; D004247:DNA; D012243:Rhodopsin