Reduction of Lipid Droplets Modulates the Injury Response and Enhances CNTF-Induced Axon Regeneration Following Optic Nerve Crush.

Source: PubMed, NCBI / U.S. National Library of Medicine

Disruption of lipid metabolism occurs in both the retina and optic nerve following optic nerve crush (ONC); however, whether the regulation of lipid droplets (LDs) influences the survival and function of retinal ganglion cells (RGCs) remains largely elusive. Here, we identified the distribution of LDs in the retina and optic nerve of ONC mice, and A922500, a selective inhibitor of diacylglycerol acyltransferase 1 (DGAT1), was applied to investigate the effect of suppressing LD biogenesis on RGC survival and visual function. The results showed that LDs were localized in Tuj1-positive cells within the retina and in IBA1-positive cells within GFAP-negative region of optic nerve following injury. A922500 significantly reduced LD accumulation and attenuated microglial density in both retina and optic nerve, but did not affect RGC survival following injury. No regenerating CTB-labeled axons were observed with A922500 monotherapy. However, combined treatment with A922500 and AAV2-CNTF enhanced axon regeneration compared to CNTF-treated alone. A922500 also significantly improved flash visual evoked potential recordings in both ONC control mice and CNTF-treated mice after injury. This study demonstrates that optic nerve crush induces LD accumulation in retinal RGC somas and in microglia at the optic nerve injury site, and reducing LDs does not preserve RGC survival but attenuates injury response, enhances CNTF-induced axon regeneration, and improves visual function.