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Matthew V. Rutar, Riccardo Natoli, Krisztina Valter, Jan M. Provis; Complement Synthesis And Propagation By Infiltrating Monocytes In Aged And Degenerative Retinas. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1225.
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Complement activation is associated with the pathogenesis of retinal dystrophies such as age-related macular degeneration (AMD). We aimed to investigate the expression and localization of a crucial component of complement, C3, in the retina during aging and in a light-induced degenerative model of atrophic AMD.
In the degenerative model, SD rats were exposed to 1000 lux of light for up to 24hrs (1, 3, 6, 12, 17, and 24hrs), after which some animals were kept in dim light (5 lux) to recover (3 and 7 days). In the aging model, SD rats were born and reared in age groups corresponding to post-natal (P) days 100, 450, and 750. For both models at their respective time-points, animals were euthanized and retinas processed. The expression of C3 was assessed by qPCR (n=3), immunohistochemistry (n=3), and in situ hybridization (n=3). Counts were made of C3-expressing monocytes using in situ hybridization (n=3). In conjunction, photoreceptor apoptosis was assessed using TUNEL labeling (n=5), as well as the expression of the stress factor GFAP (n=3). Statistical significance was determined using the Students t-test and One-way ANOVA.
In the light-damage model, a significant up-regulation (p<0.0001) of C3 was observed during and following 1000 lux light exposure, correlating with the emergence of photoreceptor death and stress factor expression (GFAP) (p<0.001). C3 expression was found to increase with age, with a significant up-regulation at P750 (p<0.05) in conjunction with increases in GFAP expression (p<0.05). In situ hybridization, coupled with immunoreactivity for the monocyte marker ED-1, revealed that C3 is expressed by infiltrating monocytes associated with the retinal vasculature and subretinal space. These increased substantially in the retina following 24hrs light-damage, and at P750 in the aging model.
Our data show that recruited monocytes actively contribute to the prolonged activation of complement in both the damaged and aging retina, though the local synthesis of C3. These findings may have relevance to the cellular events of complement activation underling the pathogenesis of AMD.
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