TY  - JOUR
AU  - Rutar, M
AU  - Valter, K
AU  - Natoli, R
AU  - Provis, JM
Y2  - 2021/02/12
Y1  - 2014/04/04
SN  - 1932-6203
UR  - http://hdl.handle.net/11343/260610
AB  - 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.
LA  - English
PB  - PUBLIC LIBRARY SCIENCE
T1  - Synthesis and Propagation of Complement C3 by Microglia/Monocytes in the Aging Retina
DO  - 10.1371/journal.pone.0093343
IS  - PLoS One
VL  - 9
IS  - 4
L1  - /bitstream/handle/11343/260610/PMC3976274.pdf?sequence=1&isAllowed=y
ER  -