Since RGCs are critical for vision, knowing what other cells influence RGCs and RGC axon survival, especially when injured, is essential. Unlike other vertebrates 3, mammals cannot spontaneously regenerate damaged axons of RGC after ON injury due to various inhibitory factors 4, 5. Given their delicate structure, ON axons are vulnerable to insult. Posterior to the ONH, the axons are myelinated by supporting oligodendrocytes, a type of glial cell. Unmyelinated RGC axons exit the eyes globe at the ON head (optic nerve head). The ON transmits signal from the eye to the brain through axons of retinal ganglion cells (RGCs), which reside in the nerve fiber layer of the neural retina. The optic nerve (ON) is a sensory nerve critical for vision. Injury or insult to CNS axons causes irreversible damage leading to neurological and neurodegenerative disorders 2. In summary, we report the first study demonstrating that AR inhibition transiently protects RGC and axon from degeneration, providing a potential therapeutic strategy for optic neuropathies.Ĭentral nervous system (CNS) axons and neurons are incapable of spontaneously regenerating in mammals 1. RNA sequencing data revealed that Sorbinil protects the retina from ONC-induced degeneration by suppressing inflammatory signaling. Moreover, Sorbinil restored RGC function and delayed axon degeneration one week after ONC. In vitro, we discovered that Sorbinil, an AR inhibitor, attenuates BV2 microglia activation and migration in the lipopolysaccharide (LPS) and monocyte chemoattractant protein-1 (MCP-1) treatments. In vivo, Sorbinil suppressed ONC-induced Iba1 + microglia/macrophage infiltration in the retina and ON and promoted RGC survival. Since aldose reductase (AR) is an inflammatory response mediator highly expressed in RMG, we investigated if pharmacological inhibition of AR can attenuate ocular inflammation and thereby promote RGC survival and axon regeneration after ON crush (ONC). In ON trauma, retinal microglia (RMG) become activated, inducing inflammatory responses and resulting in axon degeneration and RGC loss. Unfortunately, they do not regenerate upon injury in mammals. As part of the central nervous system (CNS), retinal ganglion cells (RGCs) and their axons are the only neurons in the retina that transmit visual signals from the eye to the brain via the optic nerve (ON).
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