Neuroprotective effects of naloxone against light-induced photoreceptor degeneration through inhibiting retinal microglial activation.
OBJECTIVE
To determine the role of microglial activation in light-induced photoreceptor degeneration and the neuroprotective effects of naloxone as a novel microglial inhibitor.


METHODS
Sprague-Dawley rats were exposed to intense blue light for 24 hours. Daily intraperitoneal injection of naloxone or PBS as a control was given 2 days before exposure to light and was continued for 2 weeks. Apoptotic cells were detected by the TUNEL assay, and anti-OX42 antibody was used to label retinal microglia. Western blot was applied to evaluate the retinal interleukin (IL)-1beta protein levels. Retinal histologic examination and electroretinography (ERG) were also performed to evaluate the effects of naloxone on light-induced photoreceptor degeneration.


RESULTS
TUNEL-positive cells were noted in the outer nuclear layer (ONL) of the retina as early as 2 hours and peaked at 24 hours after exposure to light. 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. Expression of IL-1beta protein was also significantly increased at 3 days. Compared with the control, the number of microglia in the outer retina was significantly decreased in the naloxone-treated group 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.


CONCLUSIONS
The activation and migration of microglia and the expression of neurotoxic factor (IL-1beta) coincide with photoreceptor apoptosis, suggesting that activated microglia play a major role in light-induced photoreceptor degeneration. Inhibiting microglial activation by naloxone significantly reduces this degeneration.
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China.
Ying-qin
YQ
Ni
Ge-zhi
GZ
Xu
Wen-zheng
WZ
Hu
Le
L
Shi
Yao-wu
YW
Qin
Cui-di
CD
Da
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D053583:Interleukin-1beta / Q000378:metabolism; D008027:Light / Q000009:adverse effects*; D008297:Male; D017628:Microglia / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation
D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D009270:Naloxone