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

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.Funding provided by Australian Research Council Centres of Excellence Program Grant (CE0561903)

Regional sea level, Southern Oscillation and beach change, New South Wales, Australia

Coastal erosion is a problem of increasing concern that affects 60% of the world\u27s sandy coastline. This erosion has been attributed to increased storminess, tectonic subsidence, eustatic sea-level rise, decreased shoreward sediment movement from the shelf, permanent longshore leakage of sediment from beach compartments, shifts in global pressure belts resulting in changes in the directional component of wave climates, and human interference. No one explanation has worldwide applicability because all factors vary in importance regionally. Evaluation of factors is complicated by a lack of accurate, continuous, long-term erosional data. Historical map evidence spanning 100-1,000 yr has been used in a few isolated areas; however, temporal resolution has not been sufficient to evaluate the effect of climatic variables. Air photographic evidence is restricted to the past 40 yr, and often suffers from insufficient ground control for accurate mapping over time. Ground surveying of beaches was rarely carried out before 1960 and is often discontinuous in time and space. I have resolved the problems of temporal and spatial continuity by studying change for the whole of Stanwell Park beach, New South Wales, Australia for the period 1895-1980 (Fig. 1). I report here that using the average high-tide wave run-up position measured accurate to ±2.5 m from oblique and vertical photographs, changes could be linked to regional sea-level variation and a globally significant climatic variable, the Southern Oscillation (SO)