June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Bisretinoid Formation and Photodegradation with Light and Dark Rearing
Author Affiliations & Notes
  • Janet R Sparrow
    Department of Ophthalmology, Columbia University, New York, NY
  • Keiko Ueda
    Department of Ophthalmology, Columbia University, New York, NY
  • Jilin Zhou
    Department of Ophthalmology, Columbia University, New York, NY
  • Zhao Liu
    Department of Ophthalmology, Columbia University, New York, NY
  • Heike Schoenherr
    Department of Ophthalmology, Columbia University, New York, NY
  • Footnotes
    Commercial Relationships Janet Sparrow, None; Keiko Ueda, None; Jilin Zhou, None; Zhao Liu, None; Heike Schoenherr, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2582. doi:
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      Janet R Sparrow, Keiko Ueda, Jilin Zhou, Zhao Liu, Heike Schoenherr; Bisretinoid Formation and Photodegradation with Light and Dark Rearing. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2582.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Given the cellular consequences of bisretinoid lipofuscin accumulation in retinal pigment epithelium (RPE), efforts have been made to elucidate mechanisms by which these compounds are damaging. In in vitro assays, bisretinoid fluorophores photodegrade releasing injurious aldehydes and dicarbonyls. To probe for evidence of photodegradation of lipofuscin in the eye, we compared levels of bisretinoid in mice that were raised in cyclic light as opposed to darkness and compared albino versus black-eyed mice.

Methods: Albino BALB/cJ, black C57BL/6J and albino C57BL/6c2j mice were raised in cyclic light or darkness. Bisretinoids were quantified by HPLC. All-trans, 13-cis, 9-cis-, and 11-cis-retinals were incubated with ethanolamine and analyzed by reverse phase UPLC. A2E and 11-cis-retinal were measured in eyecups from cyclic light-reared C57BL/6J or C57BL/6Jc2j mice that were dark-adapted before euthanasia.

Results: In BALB/cJ mice, A2E formed with both cyclic-light and dark-rearing. With housing in darkness, no differences were observed in black C57BL/6 versus albino C57BL/6c2j mice. However when the mice were maintained under cyclic light, A2E levels were reduced in the albino C57BL/6c2j mice. To adjust for increased photon catch, albino mice can reduce rhodopsin content (photostasis). Accordingly, in albino mice 11-cis retinal was lower, at age 6 and 9 months, but the extent of A2E decrease in the albino was proportionally greater. Using in vitro biosynthetic assays, we compared all-trans-retinal and various cis-isomers of retinaldehyde for their ability to form the bisretinoid conjugate A2E when reacted with ethanolamine. The percent conversion of 11-cis-retinal to total bisretinoid was 25% lower than for all-trans and 13-cis-retinals while the 9-cis-retinal isomer afforded considerably less total bisretinoid.

Conclusions: The albino mouse eye is exposed to more intraocular light than the melanin-expressing black eye. With dark-rearing, the presence or absence of ocular melanin had no effect on the levels of RPE bisretinoid lipofuscin. Conversely, In albino mice, cyclic light was associated with amounts of bisretinoid that were reduced relative to the levels observed when mice were housed in darkness. Photostasis cannot account for differences under cyclic light and dark-rearing, Photodegradative loss of the light-sensitive bisretinoid compounds likely explains the reduced lipofuscin levels in cyclic-light reared mice.


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