An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice
| Autor: | Akshay Anand, Barrett J. Rollins, Jayakrishna Ambati, William A. Kuziel, Eiji Sakurai, Bert C. Lynn, Stefan Fernandez, Balamurali K. Ambati |
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| Rok vydání: | 2003 |
| Předmět: |
Aging
CCR2 Chemokine Pathology medicine.medical_specialty genetic structures Receptors CCR2 Complement C5a Drusen Retina General Biochemistry Genetics and Molecular Biology Lipofuscin Macular Degeneration Mice chemistry.chemical_compound medicine Animals Chemokine CCL2 Inflammation biology Macrophages Monocyte Complement System Proteins General Medicine Macular degeneration medicine.disease eye diseases Vascular endothelial growth factor Choroidal neovascularization medicine.anatomical_structure chemistry Immunoglobulin G Immunology biology.protein Receptors Chemokine sense organs medicine.symptom |
| Zdroj: | Nature Medicine. 9:1390-1397 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm950 |
| Popis: | The study and treatment of age-related macular degeneration (AMD), a leading cause of blindness, has been hampered by a lack of animal models. Here we report that mice deficient either in monocyte chemoattractant protein-1 (Ccl-2; also known as MCP-1) or its cognate C-C chemokine receptor-2 (Ccr-2) develop cardinal features of AMD, including accumulation of lipofuscin in and drusen beneath the retinal pigmented epithelium (RPE), photoreceptor atrophy and choroidal neovascularization (CNV). Complement and IgG deposition in RPE and choroid accompanies senescence in this model, as in human AMD. RPE or choroidal endothelial production of Ccl-2 induced by complement C5a and IgG may mediate choroidal macrophage infiltration into aged wild-type choroids. Wild-type choroidal macrophages degrade C5 and IgG in eye sections of Ccl2(-/-) or Ccr2(-/-) mice. Impaired macrophage recruitment may allow accumulation of C5a and IgG, which induces vascular endothelial growth factor (VEGF) production by RPE, possibly mediating development of CNV. These models implicate macrophage dysfunction in AMD pathogenesis and may be useful as a platform for validating therapies. |
| Databáze: | OpenAIRE |
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