Intravitreal injection of SARM1 siRNA in TNF-induced optic nerve degeneration

Intravitreal injections of some drugs such as anti-VEGF antibodies are available for certain human ocular diseases. Meanwhile, inhibition of SARM1 has been reported to exert neuroprotection in several neurodegenerative disease models. The aim of the current study is to investigate whether intravitreal injection of SARM1 siRNA can protect axons against TNF-induced optic nerve degeneration model.

Rats were received with intravitreal injection of PBS, TNF, TNF + SARM1 siRNA or SARM1 siRNA alone. Pre-injection of SARM1 siRNA + TNF and pre-injection of control siRNA + TNF groups were also made. Immunoblot analysis was carried out to evaluate SARM1 expression in the optic nerve. Morphometric analysis was carried out to evaluate the effects of SARM1 siRNA against axon loss induced by TNF. Immunohistochemical analysis was carried out to examine the localization of SARM1 in cross-sectioned optic nerves.

Immunoblot analysis showed that intravitreal injection of SARM1 siRNA significantly decreased the SARM1 protein level in the optic nerve. Unexpectedly, axonal loss in the simultaneous intravitreal injection of SARM1 and TNF was almost the same as that in the TNF injection alone group. Pre-injection of SARM1 siRNA did not prevent axonal loss induced by TNF. There were no changes in SARM1 protein level in optic nerves 1 week after TNF injection compared with the PBS-injected group. Immunohistochemical analysis showed that the SARM1 immunoreactivity was colocalized with GFAP immunoreactivity in cross-sectioned optic nerves in both TNF and control groups.

These results suggest that intravitreal injection of SARM1 siRNA may not prevent axonal degeneration induced by TNF.