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

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.

• 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)

Chemical References

• Chemokines
• Complement C3
• Glial Fibrillary Acidic Protein

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)