Conclusions
Elevated SARM1 expression was observed in the optic nerves in both the COH and I/R injury models. Downregulation of SARM1 exhibited a protective effect on RGC soma and axons in the COH model, with JNK identified as a downstream regulator of SARM1 in this context.
Methods
The COH model was induced by injecting magnetic microbeads into the anterior chamber, whereas the acute model was created through ischemia-reperfusion (I/R) injury. Immunohistochemistry and Western blot were used to assess SARM1 expression and JNK phosphorylation in the retina and optic nerve. SARM1 downregulation was achieved through the intravitreal injection of adeno-associated virus (AAV)2-shRNA. Quantitative analysis of RGC survival was performed by the counting of Brn3A-positive RGCs, and surviving axons were assessed through optic nerve toluidine blue stain.
Purpose
This study aimed to assess the expression of sterile alpha and TIR motif containing protein 1 (SARM1) in both chronic and acute glaucomatous animal models and investigate the underlying SARM1-JNK signaling mechanism responsible for the protective effects of SARM1 downregulation on retinal ganglion cell (RGC) soma and axons in a chronic intraocular hypertension (COH) model.
Results
The expression of SARM1 increased 1 week after microbead injection in the optic nerve, whereas the retinal SARM1 expression decreased at 3 days post-injection in the COH model. After 24 hours of reperfusion, SARM1 expression increased in both the optic nerves and the retinas in the I/R injury model. SARM1 downregulation led to increased survival of RGC soma and axons in the COH model. In this model, JNK phosphorylation was significantly reduced concomitant with decreased SARM1 expression. Conclusions: Elevated SARM1 expression was observed in the optic nerves in both the COH and I/R injury models. Downregulation of SARM1 exhibited a protective effect on RGC soma and axons in the COH model, with JNK identified as a downstream regulator of SARM1 in this context.