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Tomohiro Okamoto, Mamoru Kamoshita, Hideto Osada, Eriko Toda, Toshihide Kurihara, Norihiro Nagai, Kazuo Tsubota, Yoko Ozawa; Neuroprotective effect of rapamycin in the retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):435.
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© ARVO (1962-2015); The Authors (2016-present)
Rapamycin is an inhibitor of PI3K/Akt/mTOR pathway that is widely used in the medical field. It has immunosuppressive, anti-cancer, and life extending effects. In this study, we investigated the neuroprotective effect of rapamycin in the retina of lipopolysaccharide (LPS) -induced uveitis and retinitis (EIU) model mice.
Six-week old C57BL/6 mice received a single intraperitoneal injection of LPS to generate the EIU model. Rapamycin was administered by intraperitoneal injection 1 hour after LPS injection, and an autophagy inhibitor, 3-methyladenine (3-MA), was 30 minutes after rapamycin administration. Twenty-four hours after LPS injection, visual function was analyzed by electroretinogram (ERG), and the protein and mRNA levels of rhodopsin were measured by immunoblot analysis and real time RT-PCR, respectively.
Compared with the control mice, the amplitude of the a-wave and b-wave in ERG were reduced in EIU mice treated by control vehicle. However, the reduction was attenuated in the EIU mice treated by rapamycin. The level of rhodopsin protein was reduced in the vehicle treated EIU mice, however, it was preserved in the rapamycin treated EIU mice. The mRNA level of rhodopsin showed no change. Interestingly, the protein level reduced in the retina of EIU mice treated by 3-MA in addition to rapamiycin.
Rapamycin treatment prevented visual function impairment and the post-transcriptional reduction of rhodopsin protein in the retina of EIU model mice. Autophagy was most likely involved in the underlying mechanism. Further studies will help understand the pathogenesis of retinal inflammation and the neuroprotective effect of rapamycin in the retina.
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