Synthesis and propagation of complement C3 by microglia/monocytes in the aging retina

• Published in: PloS one 2014-04, Vol.9 (4), p.e93343-e93343
• Main Authors: Rutar, Matt, Valter, Krisztina, Natoli, Riccardo, Provis, Jan M
• Format: Article
• Language: English
• Subjects: Age; Age related diseases; Aging; Aging (natural); Aging - genetics; Aging - metabolism; Analysis; Animals; Animals, Newborn; Biology and Life Sciences; Cell activation; Chemokines; Chemokines - genetics; Chemokines - metabolism; Complement; Complement activation; Complement C3 - genetics; Complement C3 - metabolism; Complement component C3; Disease; Gene amplification; Gene expression; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - genetics; Glial Fibrillary Acidic Protein - metabolism; Health aspects; Homeostasis; Immunology; Inflammation; Intermediate filament proteins; Localization; Macular degeneration; Medical research; Medicine and Health Sciences; Microglia; Microglia - metabolism; Monocytes; Monocytes - metabolism; mRNA; Pathogenesis; Photoreceptors; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Retina; Retina - cytology; Retina - physiology; RNA; Studies; Thinning
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0093343

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. 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. 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. 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.