| Purpose: Resident microglia are involved in stress responses of the central nervous system and contribute to neuronal degeneration.This study was conducted to explore the role that retinal microglia play in light-induced photoreceptor degeneration and evaluate the neuroprotective effect of Naloxone as a microglia inhibitor.
Methods: Sprague-Dawley rats accepted dark adaptation prior to light exposure of 24 h at 2.5 Klux. The animals received intraperitoneal injections of Naloxone or PBS 2 days before light exposure for 2 weeks. TUNEL assay and mouse-anti-rat OX42 antibody were used to detect DNA fragmentation and label retinal microglia. Western-blot were used to evaluate the IL-1ß protein level of the retina. Morphologic, electrophysiological and immunohistochemical studies were performed to evaluate the efficacy of naloxone in the amelioration of light-induced retinal degeneration and the possible involvement of microglial cells.
Results: After intense light exposure, TUNEL-positive cells were noted in the outer nuclear layer (ONL) of the retina as early as 2 h and reached the peak at 1 day. In contrast OX42-positive cells assumed a more ameboid configuration were seen in the ONL at 6 h and and increased significantly at 1 day and 3 days, so as the retinal IL-1ß protein expression. Naloxone treatment provided marked amelioration in the loss of photoreceptors in light-induced retinal degeneration, as evidenced by morphologic and electrophysiologic criteria. Morphologically,the Naloxone-treated group showed markedly preservation of the ONL thickness 14 days after exposure to light(P<0.001) .At the same timepoint, electroretinography (ERG) showed that Naloxone significantly preserved the amplitudes of dark-adapted a- and b-wave, which were all markedly reduced after photic injury.The microglia in the ONL and subretinal space in Naloxone-treated group at 3 days after light exposure were significantly decreased when compared with those in the light-exposed, PBS-treated control group (P<0.01).
Conclusions: Activation and migration of retinal microglia, as well as expression of microglia-derived toxic factor(IL-1ß), coincides with photoreceptor apopotosis, suggesting activated microglia play a major role in photoreceptor degeneration. Systemic infusion of Naloxone significantly reduced the light-induced loss of photoreceptors possibly through inhibiting the activation of microglia.
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