Paper

Ccl2/Cx3cr1-Deficient Mice: An Animal Model for Age-Related Macular Degeneration
Chi-Chao Chan^a, Robert J. Ross^a, Defen Shen^a, Xiaoyan Ding^a, Zigurts Majumdar^b, Christine M. Bojanowski^a, Min Zhou^a, Norman Salem, Jr.^c, Robert Bonner^b, Jingsheng Tuo<sup>a

a</sup>Section of Immunopathology, Laboratory of Immunology, National Eye Institute,
^bSection on Medical Biophysics, Laboratory of Integrative and Medical Biophysics, National Institute of Child Health and Human Development, and
^cLaboratory of Membrane Biochemistry and Biophysics, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Md., USA

Address of Corresponding Author

Ophthalmic Res 2008;40:124-128 (DOI: 10.1159/000119862)

  Key Words

• Age-related macular degeneration
• Animal model
• CCL2
• CX3CR1
• Retinal pigment epithelium
• N-retinylidene-N-retinylethanolamine
• Chaperone
• Omega-3 long-chain polyunsaturated fatty acids

  Abstract

Background/Aims: Senescent Ccl2^-/- mice develop cardinal features of human age-related macular degeneration (AMD). Loss-of-function single-nucleotide polymorphisms within CX3CR1 are associated with AMD. Methods: We generated Ccl2^-/-/Cx3cr1^-/- [double-knockout (DKO)] mice and evaluated the eyes using fundoscopy routine histology, immunochemistry, biochemistry and proteomics. Results: At 6 weeks old, all DKO mice developed AMD-like retinal lesions such as abnormal retinal pigment epithelium cells, drusen, photoreceptor atrophy and choroidal neovascularization, which progressed with age and reversed with high omega-3 long-chain polyunsaturated fatty acid diet. N-retinylidene-N-retinylethanolamine (A2E), a major lipofuscin fluorophore, illustrated by an emission peak at ~600 nm, was significantly higher in DKO retinal pigment epithelium. Decreased ERp29 was found in the retina of DKO mice. Conclusion: A broad spectrum of AMD pathologies with early onset and high penetrance in these mice implicate certain chemokines, A2E and endoplasmic reticulum proteins in AMD pathogenesis.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Chi-Chao Chan, MD
Building 10, Room 10N103
10 Center Drive, NIH/NEI
Bethesda, MD 20892-1857 (USA)
Tel. +1 301 496 0417, Fax +1 301 402 8664, E-Mail chanc@nei.nih.gov

  Article Information

Published online: April 18, 2008
Number of Print Pages : 5
Number of Figures : 5, Number of Tables : 0, Number of References : 24