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Y. Ni, G.-Z. Xu, W.-Z. Hu, P.-Q. Zhao, L. Shi, Y.-W. Qin; A Novel Neuroprotective Effect of Naloxone in Light-Induced Photoreceptor Degeneration Through Inhibiting Activation of Retinal Microglia. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4413. doi: https://doi.org/.
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To study the role of microglia activation and migration in light-induced photoreceptor degeneration and evaluate the novel neuroprotective effect of naloxone as a microglia inhibitor.
Sprague-Dawley rats received light exposure at 2500 lux for 24 hours. Daily intraperitoneal injection of naloxone or PBS was started 2 days before light exposure and lasted for 2 weeks. TUNEL staining and anti-OX42 antibody were used to detect DNA fragmentation and label retinal microglia. Western-blot was used to evaluate the protein level of IL-1ß in retina. Retinal histology, immunohistochemistry and electroretinography were performed to evaluate the effect of naloxone in light-induced photoreceptor degeneration.
TUNEL-positive cells were noted in the outer nuclear layer (ONL) as early as 2 hours and reached the peak at 24 hours after light exposure. OX42-positive microglia occurred in the ONL and subretinal space at 6 hours, peaked at 3 days, and changed morphologically from the resting ramified to the activated amoeboid. The protein expression of IL-1ß was also increased significantly at 3 days. Compared to the PBS control group, TUNEL-positive cells in the ONL were significantly decreased in the naloxone-treated group at 3 and 7 days but no different at 1 day with microglia migrated in the outer retina decreased at 3 days; and the thickness of ONL and the amplitudes of dark-adapted a- and b-waves were also well preserved at 14 days.
Activation and migration of retinal microglia, as well as expression of neurotoxic factor(IL-1ß), coincides with photoreceptor apopotosis, suggesting activated microglia play a major role in photoreceptor degeneration. Naloxone protects against further degeneration of photoreceptors after light damage by inhibiting the microglial activation.
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