May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The All-Trans-Retinal Dimer Series of RPE Lipofuscin Pigments
Author Affiliations & Notes
  • J. Zhou
    Ophthalmology, Columbia University, New York, New York
  • S. Kim
    Ophthalmology, Columbia University, New York, New York
  • B. Westlund
    Ophthalmology, Columbia University, New York, New York
  • Y. Jang
    Pharmacy, Kyung Hee University, Seoul, Republic of Korea
  • J. Sparrow
    Ophthalmology, Columbia University, New York, New York
  • Footnotes
    Commercial Relationships  J. Zhou, None; S. Kim, None; B. Westlund, None; Y. Jang, None; J. Sparrow, None.
  • Footnotes
    Support  NIH Grant EY12951 (to J.R.S.)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 222. doi:https://doi.org/
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    • Get Citation

      J. Zhou, S. Kim, B. Westlund, Y. Jang, J. Sparrow; The All-Trans-Retinal Dimer Series of RPE Lipofuscin Pigments. Invest. Ophthalmol. Vis. Sci. 2008;49(13):222. doi: https://doi.org/.

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

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Abstract

Purpose: : We have presented two biosynthetic pathways by which all-trans-retinal can form RPE lipofuscin pigments, one leading to A2E formation and the other generating the all-trans-retinal dimer (atRAL dimer) series of compounds, including unconjugated all-trans-retinal dimer (atRAL dimer), atRAL dimer-PE and atRAL dimer-E (Fishkin et al., PNAS 2005; Kim et al., PNAS 2007). We showed that atRAL dimer is a more efficient generator of singlet oxygen than is A2E and in Abcr-/- mice levels of atRAL dimer-PE exceed that of A2E. While A2E is a pyridinium salt with a quaternary amine nitrogen that does not deprotonate/reprotonate, the imine nitrogen of atRAL dimer-E and atRAL dimer-PE protonates/deprotonates in a pH-dependent fashion. Here we report additional studies related to the photooxidation of these bisretinoid compounds.

Methods: : atRAL dimer, atRAL dimer-E and atRAL dimer-PE and oxidized-atRAL dimer (oxo-atRAL dimer) were synthesized. Reverse-phase HPLC analysis was performed with UV-visible and fluorescence detection. Mouse eyecups were extracted with chloroform/methanol for analysis. Complement activation was monitored using enzyme immunoassay to measure the C3 split product iC3b in undiluted serum incubated (37°C) in wells precoated with atRAL dimer, peroxy-atRAL dimer and furano-atRAL dimer. iC3b generation in normal human serum (NHS) was compared to that in factor B-depleted human serum.

Results: : Oxo-atRAL dimer exhibited more pronounced fluorescence (excitation, 430 nm; emission, 600 nm) than atRAL dimer. In a comparison of pigmented and albino Abcr-/- mice, no differences in levels of atRAL dimer (pmoles/eye) were observed; however, oxo-atRAL dimer was increased in albino mouse eyecups relative to pigmented mice . Oxo-atRAL dimer was also more abundant than atRAL dimer. iC3b was also increased in serum incubated in wells pre-coated with atRAL dimer and oxo-atRAL dimer(peroxy- atRAL dimer and furano- atRAL dimer). Substitution of NHS with factor B-depleted human sera containing 20 mM calcium and magnesium abrogated the increase in iC3b.

Keywords: age-related macular degeneration • retinal pigment epithelium • ipofuscin 
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