May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Lipid Deposits, Retinal Pigment Epithelium Dysfunction and Photoreceptor Degeneration: An Acute Rat Model of Dry Age-Related Macular Degeneration
Author Affiliations & Notes
  • Y. Zhang
    Novartis Institute for Biomedical Research, Cabridge, Massachusetts
  • A. De Erkenez
    Novartis Institute for Biomedical Research, Cabridge, Massachusetts
  • J. Demirs
    Novartis Institute for Biomedical Research, Cabridge, Massachusetts
  • B. Jaffee
    Novartis Institute for Biomedical Research, Cabridge, Massachusetts
  • Footnotes
    Commercial Relationships Y. Zhang, novartis, E; A. De Erkenez, novartis, E; J. Demirs, novartis, E; B. Jaffee, novartis, E.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3017. doi:
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      Y. Zhang, A. De Erkenez, J. Demirs, B. Jaffee; Lipid Deposits, Retinal Pigment Epithelium Dysfunction and Photoreceptor Degeneration: An Acute Rat Model of Dry Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3017.

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

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Abstract

Purpose:: The lack of suitable animal models has hampered development of pharmaceutical therapy for dry age-related macular degeneration (AMD). For rapid compound screening and preclinical assessments, an adequate acute model is required. This study aims to develop a rat model of dry AMD with rapid disease development.

Methods:: Intravenous injection of a single dose of NaIO3 was given to the tail vein of Sprague-Dawley rats (6 to 8 weeks old). At 5 and 6 days post NaIO3 injection, LDL cholesterol was injected intravenously. Age-matched rats after a single iv of PBS, NaIO3 or Cholesterol served as controls. Seven days after first injection, rats were sacrificed, and the eyes were subjected to histological analysis. RPE cells were visualized by RPE 65 immunocytochemistry, and tight junction of RPE cells were examined in RPE/sclera whole mounts. Apoptosis was evaluated by TUNEL assay. Lipid deposits were detected by Oil-Red and filipin staining.

Results:: After NaIO3 and cholesterol injections, large number of RPE cells appeared swollen or degenerated, and junction integrity was disrupted in the central retina. Lipid-positive deposits were found widespread in the damaged regions of RPE cells. TUNEL-positive cells were identified frequently in the photoreceptor layer. After NaIO3 injection alone, a similar damage on RPE and photoreceptor could be seen. However, very few lipid deposits were found. Little, if any, pathological changes were found in other controls (single injection of cholesterol or PBS).

Conclusions:: Intravenous injections of NaIO3 followed by cholesterol induced pathological changes in the retina that represent pathology similar to human dry AMD. This model has fast onset, and may serve as a useful tool to evaluate compounds for dry AMD.

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