title: Light damage in Abca4 and Rpe65rd12 mice.
abstract: OBJECTIVE
  Bisretinoids form in photoreceptor cells and accumulate in retinal pigment epithelium (RPE) as lipofuscin. To examine the role of these fluorophores as mediators of retinal light damage, we studied the propensity for light damage in mutant mice having elevated lipofuscin due to deficiency in the ATP-binding cassette (ABC) transporter Abca4 (Abca4(-/-) mice) and in mice devoid of lipofuscin owing to absence of Rpe65 (Rpe65(rd12)).
  
  
  METHODS
  Abca4(-/-), Rpe65(rd12), and wild-type mice were exposed to 430-nm light to produce a localized lesion in the superior hemisphere of retina. Bisretinoids of RPE lipofuscin were measured by HPLC. In histologic sections, outer nuclear layer (ONL) thickness was measured as an indicator of photoreceptor cell degeneration, and RPE nuclei were counted.
  
  
  RESULTS
  As shown previously, A2E levels were increased in Abca4(-/-) mice. These mice also sustained light damage-associated ONL thinning that was more pronounced than in age-matched wild-type mice; the ONL thinning was also greater in 5-month versus 2-month-old mice. Numbers of RPE nuclei were reduced in light-stressed mice, with the reduction being greater in the Abca4(-/-) than wild-type mice. In Rpe65(rd12) mice bisretinoid compounds of RPE lipofuscin were not detected chromatographically and light damage-associated ONL thinning was not observed.
  
  
  CONCLUSIONS
  Abca4(-/-) mice that accumulate RPE lipofuscin at increased levels were more susceptible to retinal light damage than wild-type mice. This finding, together with results showing that Rpe65(rd12) mice did not accumulate lipofuscin and did not sustain retinal light damage, indicates that the bisretinoids of retinal lipofuscin are contributors to retinal light damage.
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Keiko
authors.initials: K
authors.lastname: Ueda
authors.forename: Taka
authors.initials: T
authors.lastname: Nagasaki
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D008027:Light / Q000009:adverse effects*; D008062:Lipofuscin / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*
chemical_list: D018528:ATP-Binding Cassette Transporters; C512841:Abca4 protein, mouse; D008062:Lipofuscin; D004247:DNA
keywords: Abca4; bisretinoid; light; lipofuscin; retina; retinal degeneration; retinal pigment epithelium