April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Unique Photoreceptor Cell Death Profile In All-trans-retinal-associated Retinal Degeneration
Tadao Maeda; Kiichiro Okano; Yu Chen; Vishal Chauhan; Grazyna Palczewska; Akiko Maeda; Krzysztof Palczewski
Author Affiliations & Notes
  • Tadao Maeda
    Ophthalmology and Visual Sciences,
    Case Western Reserve University, Cleveland, Ohio
  • Kiichiro Okano
    Ophthalmology and Visual Sciences,
    Case Western Reserve University, Cleveland, Ohio
  • Yu Chen
    Pharmacology,
    Case Western Reserve University, Cleveland, Ohio
  • Vishal Chauhan
    Ophthalmology and Visual Sciences,
    Case Western Reserve University, Cleveland, Ohio
  • Grazyna Palczewska
    Polgenix, Inc., Cleveland, Ohio
  • Akiko Maeda
    Ophthalmology and Visual Sciences,
    Case Western Reserve University, Cleveland, Ohio
  • Krzysztof Palczewski
    Pharmacology,
    Case Western Reserve University, Cleveland, Ohio
  • Footnotes
    Commercial Relationships  Tadao Maeda, None; Kiichiro Okano, None; Yu Chen, None; Vishal Chauhan, None; Grazyna Palczewska, None; Akiko Maeda, None; Krzysztof Palczewski, None
  • Footnotes
    Support  EY008061, EY009339, EY019880, EY019031, EY020715 and P30 EY11373
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 953. doi:
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      Tadao Maeda, Kiichiro Okano, Yu Chen, Vishal Chauhan, Grazyna Palczewska, Akiko Maeda, Krzysztof Palczewski; Unique Photoreceptor Cell Death Profile In All-trans-retinal-associated Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):953.

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Abstract

Purpose: : To study the pathological functions of cone and rod photoreceptor cells in light-induced retinal degeneration associated with accumulation of toxic all-trans-retinal and its associated condensation products such as diretinoid-pyridinium-ethanolamine (A2E).

Methods: : We prepared light-induced retinal degeneration mouse models with rod-rich or cone-rich retina by genetically ablating with cone-DTA (cone-specific diphtheria toxin A) transgene or deletion of Nrl (rod photoreceptor-specific neural retina leucine zipper protein gene) in a Rdh8-/-Abca4-/-mouse background, in which clearance of all-trans-retinal is impaired, to examine the contribution of rods and cones to light-induced photoreceptor degeneration under different light conditions. Morphological changes in the retina were evaluated by histological techniques and in vivo ophthalmological imaging systems (scanning laser ophthalmoscope: SLO, spectral domain-optical coherence tomography: SD-OCT). Physiological and biochemical functions in the retina were investigated by electroretinography (ERG) and retinoid analysis.

Results: : Nrl-/-Rdh8-/-Abca4-/-(cone-rich) and cone-DTARdh8-/-Abca4-/- (rod-rich) retinas showed much milder degeneration compared with Rdh8-/-Abca4-/- retina (cone and rod) under a regular light cycle at 3 months of age. Although these three mouse models displayed progression in their retinal degeneration by the age of 6 months, cone-DTARdh8-/-Abca4-/- retina showed slower progression than Nrl-/-Rdh8-/-Abca4-/-and Rdh8-/-Abca4-/- retinas. After intense light exposure, photoreceptors in cone-DTA Rdh8-/-Abca4-/- and Rdh8-/-Abca4-/- retinas were severely degenerated whereas no significant photoreceptor cell death was observed in Nrl-/-Rdh8-/-Abca4-/- retina. Different amounts of A2E were detected in these animals.

Conclusions: : Progression of retinal degeneration induced by delayed clearance of all-trans-retinal was affected by the population density of rod and cone photoreceptors. This suggests that macular-specific distribution of cone/rod cells may dictate the characteristic photoreceptor degeneration observed in human age-related macular degeneration.

Keywords: age-related macular degeneration • retinoids/retinoid binding proteins • ipofuscin 
© 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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