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M. V. Rutar, R. Natoli, K. Valter, J. M. Provis; Mechanisms of Neuroinflammatory Activation by the Neural Retina Following Light-Induced Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2250.
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To investigate the expression and localization of potent inflammatory markers from the chemokine and complement system pathways in the neural retina following photoreceptor death induced by excessive light.
SD rats were exposed to 1000lx of light for up to 24hrs, after which some animals were kept in dim light (5 lux) to recover. At specific time points during exposure (1, 3, 6, 12, 17, and 24hrs) and following exposure (3 and 7 days), animals were euthanized and retinas processed. The expression of the monocyte chemoattractant chemokine CCL-2, and an array of complement system components (C1s, C3, and C5) and receptors (C1qR, C3aR, C5aR), were assessed by qPCR (n=4), immunohistochemistry (n=3), and in situ hybridization (n=3). In conjunction, counts were made of monocytes on retinal cryo-sections immunolabeled with ED1 (n=3), and photoreceptor cell apoptosis was assessed using TUNEL labeling (n=5). Statistical significance was determined using the Students t-test and One-way ANOVA.
Up-regulation of CCL-2 gene expression was evident in retinal tissue, and reached a maximum at 24hrs, which correlated with the increase (p<0.05) in photoreceptor cell death. Immunohistochemistry and in situ hybridization on retinal cryo-sections revealed that CCL-2 is expressed by Müller cells, predominately in regions of heavy photoreceptor degeneration. In conjunction, a significant (p<0.05) localized recruitment of monocytes to the choroidal and retinal vascular supplies from 24hrs exposure was observed. A significant up-regulation (p<0.0001) of complement genes C3, C1s, C3aR, C1qR, and C5aR was observed during and following the course of light exposure, correlating with significant increases in photoreceptor death (p<0.001).
Our data indicate that the retina actively contributes to the guidance of the neuroinflammatory response following retinal injury, through the local expression of inflammatory factors from both chemokine and complement pathways. Characterization of the immune response of the neural retina is crucial in clarifying the underling pathogenesis of inflammation in retinal degeneration.
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