Preventive effects of rapamycin on inflammation and capillary degeneration in a rat model of NMDA-induced retinal injury.
Inhibitors of the mammalian target of rapamycin (mTOR) have been shown to protect against neuronal injury, but the mechanisms underlying this effect are not fully understood. The present study aimed to examine the effects of rapamycin, an inhibitor of the mTOR pathway, on inflammation and capillary degeneration in a rat model of N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity. Inflammation and capillary degeneration were evaluated by counting the numbers of CD45-positive leukocytes and Iba1-positive microglia, and by measuring the length of empty basement membrane sleeves, respectively. Marked increases in the numbers of leukocytes and microglia were observed 1 d after intravitreal injection of NMDA (200 nmol), and significant capillary degeneration was observed after 7 d. These NMDA-induced changes were significantly reduced by the simultaneous injection of rapamycin (20 nmol) with NMDA. These results suggest that rapamycin has preventive effects on inflammation and capillary degeneration during retinal injury.
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences.
Yuto
Y
Aoki
Tsutomu
T
Nakahara
Daiki
D
Asano
Hiroko
H
Ushikubo
Asami
A
Mori
Kenji
K
Sakamoto
Kunio
K
Ishii
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D008297:Male; D016202:N-Methylaspartate; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D020123:Sirolimus / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D016202:N-Methylaspartate; D020123:Sirolimus