April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Accumulation of Toxic Retinal Fluorophores in Various Degenerative Retinal Diseases
Author Affiliations & Notes
  • T. V. Bui
    Sirion Therapeutics, Inc., San Diego, California
  • N. Tsivkovskaia
    Sirion Therapeutics, Inc., San Diego, California
  • N. L. Mata
    Sirion Therapeutics, Inc., San Diego, California
  • Footnotes
    Commercial Relationships  T.V. Bui, Sirion Therapeutics, E; N. Tsivkovskaia, Sirion Therapeutics, E; N.L. Mata, Sirion Therapeutics, E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4188. doi:
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    • Get Citation

      T. V. Bui, N. Tsivkovskaia, N. L. Mata; Accumulation of Toxic Retinal Fluorophores in Various Degenerative Retinal Diseases. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4188.

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

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Abstract

Purpose: : Excessive accumulation of lipofuscin and toxic retinal fluorophores has been previously observed in post-mortem donor eyes of patients with Stargardt’ disease. It is not clear whether retinal fluorophores play a role in the pathogenesis of other degenerative retinal diseases. In this study, we have examined post-mortem donor eyes representing four distinct retinal diseases in order to determine whether lipofuscin accumulation is correlated with the appearance and accretion of toxic retinal fluorophores.

Methods: : Post-mortem human donor eyes were received from a local eye bank and processed within 24 hours of procurement. The ocular disease indications of these donors included: AMD, diabetes mellitus (type II), ocular albinism, and glaucoma. Approximately age-matched normal donor eyes were used for comparison. Retinal fluorophores and retinoids were extracted from the samples and analyzed using established techniques. In some cases, histological examination was also performed.

Results: : Elevated levels of A2E, and related fluorophores, were found in the RPE of each diseased donor eye. Fluorophore levels in normal tissues were consistently below that found in diseased tissues. Interestingly, the highest fluorophore levels were observed in patients with ocular albinism, followed by AMD, diabetes mellitus II, and glaucoma. Thus, it appears that the absence of melanin contributes to fluorophore accumulation. It is also noteworthy that A2E was elevated in both dry and wet AMD specimens. Thus, A2E accumulation may be implicated in the pathogenesis of both disease states. Histological examinations showed compromised RPE structure in all diseased eyes.

Conclusions: : We have found that A2E and related fluorophores accumulate in each disease indication examined. This finding suggests a shared pathological mechanism among these diseases. Each of these diseases is characterized by RPE dysfunction which compromises the ability to degrade and recycle retinal debris. Moreover, current therapies directed at reducing A2E accumulation in AMD patients may be applicable to any degenerative retinal disease which is characterized by lipofuscin accumulation.

Keywords: age-related macular degeneration • retinal pigment epithelium 
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