Abstract | INTRODUCTION: Complement activation is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which may be mediated in part by para-inflammatory processes. We aimed to investigate the expression and localization of C3, a crucial component of the complement system, in the retina during the course of aging. METHODS: SD rats were born and reared in low-light conditions, and euthanized at post-natal (P) days 100, 450, or 750. Expression of C3, IBA1, and Ccl- and Cxcl- chemokines was assessed by qPCR, and in situ hybridization. Thickness of the ONL was assessed in retinal sections as a measure of photoreceptor loss, and counts were made of C3-expressing monocytes. RESULTS: C3 expression increased significantly at P750, and correlated with thinning of the ONL, at P750, and up-regulation of GFAP. In situ hybridization showed that C3 was expressed by microglia/monocytes, mainly from within the retinal vasculature, and occasionally the ONL. The number of C3-expressing microglia increased significantly by P750, and coincided spatiotemporally with thinning of the ONL, and up-regulation of Ccl- and Cxcl- chemokines. CONCLUSIONS: Our data suggest that recruited microglia/monocytes contribute to activation of complement in the aging retina, through local expression of C3 mRNA. C3 expression coincides with age-related thinning of the ONL at P750, although it is unclear whether the C3-expressing monocytes are a cause or consequence. These findings provide evidence of activation of complement during natural aging, and may have relevance to cellular events underling the pathogenesis of age-related retinal diseases.
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Authors | Matt Rutar, Krisztina Valter, Riccardo Natoli, Jan M Provis |
Journal | PloS one
(PLoS One)
Vol. 9
Issue 4
Pg. e93343
( 2014)
ISSN: 1932-6203 [Electronic] United States |
PMID | 24705166
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chemokines
- Complement C3
- Glial Fibrillary Acidic Protein
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Topics |
- Aging
(genetics, metabolism)
- Animals
- Animals, Newborn
- Chemokines
(genetics, metabolism)
- Complement C3
(genetics, metabolism)
- Glial Fibrillary Acidic Protein
(genetics, metabolism)
- Microglia
(metabolism)
- Monocytes
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Retina
(cytology, physiology)
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