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Venu Talla, Vittorio Porciatti, John Guy; Rapamycin Treatment Inhibits the Progression of Optic Neuritis Mediated Visual Loss in Experimental Autoimmune Encephalomyelitis (EAE) Mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5093.
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© ARVO (1962-2015); The Authors (2016-present)
To study the effect of the mTOR inhibitor rapamycin on retinal ganglion cell axonal degeneration, visual loss and optic neuropathy in EAE mouse model.
EAE was induced in Female DBA1J mice by subdermal injection of 0.1 ml homologous spinal cord emulsion in complete Freunds adjuvant. Mice injected with complete Freunds adjuvant and age-matched normal mice were used as controls. Visual function was assessed by pattern electroretinograms (PERGs) at 1, 4 and 7 month post sensitization (MPS). Upon the decrease in PERG, mice were randomly divided into two groups. Group one received intraperitoneal injection of rapamycin (8.0 mg/Kg body weight) everyday for 30 days, whereas group two received only vehicle. One month later visual function was assessed by recording the PERG. Spectral domain OCT evaluated thickness of the inner plexiform layer to nerve fiber layer. Mice were euthanized at 9MPS, retinal ganglion cell (RGC) and mitochondrial numbers were evaluated by Tuj1 and GRIM19 staining on retinal whole mounts. The regenerative ability of the RGC axons were evaluated by GAP43 staining.
PERG analysis at 7MPS indicated decrease in amplitudes by 27% in EAE mice compared to CFA control (p=0.0002). There was no significant change in PERG amplitude of pretreatment verses post rapamycin treated EAE mice. However, PERG amplitude in vehicle treated EAE mice was decreased by 31% (p=0.01) compared to pretreatment. Rapamycin injections prevented the loss of amplitudes by 100% compared to EAE vehicle treatment. OCT showed rescue of inner retinal thickness in rapamycin treated group that was comparable to CFA control whereas, it is thinner by 14% in vehicle treated EAE mice (p<0.0001). RGCs were preserved in rapamycin treated EAE mice and comparable to CFA control whereas, there was a decrease by 21.4% (p<0.001) in vehicle treated EAE mice. Mitochondrial numbers were found to be higher in rapamycin treated group (p=0.03) whereas, they were comparable to CFA control in EAE vehicle group.
Rapamycin may be useful for reducing neurodegeneration associated with permanent visual loss in optic neuritis and multiple sclerosis patients.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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