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Eye disease: switching signals for repairing injured optic nerves Regulating molecular signaling pathways that control the degradation of cellular components—a process known as autophagy—could offer a new approach to treating optic nerve damage after traumatic injuries. There is currently no established treatment option for traumatic optic nerve injury. Rong-Kung Tsai and colleagues at Tzu Chi University in Hualien, Taiwan, explored the role of a protein complex called mTORC2 in autophagy during the repair of optic nerves in rats. They investigated mTORC2 activation by small RNA molecules that also activate autophagy, and by drugs that activate autophagy but inhibit mTORC2. The results indicate that autophagy associated with activation of mTORC2 protects damaged retinal neurons and promotes visual recovery. In addition to treating optic nerve injuries, drugs activating mTORC2 and autophagy might help treat nerve-related diseases of the eye, including glaucoma.

Astaxanthin, a xanthophyll belonging to the family of carotenoids, is a potent antioxidant. However, much less is known about its protective effects on the oxidative stress of ischemic optic nerve. We hypothesized that astaxanthin treatment could protect retinal ganglion cells (RGCs) from death via anti-oxidative and anti-apoptotic responses. Adult male Wistar rats were fed astaxanthin (100 mg/kg/day) by daily gavage for seven consecutive days, either before or after inducing oxidative stress in the retina by photodynamic treatment. The visual function, RGC apoptosis, macrophage infiltration in the optic nerve, expression of p-Akt, p-mTOR, SGK1, pS6K, Nrf2, p62, TNFα, Il1β in retinas were investigated. The visual function and the RGC densities were significantly higher in both pre- and post-treatment groups. The numbers of apoptotic RGCs and extrinsic macrophage infiltration in the optic nerve were significantly decreased in both astaxanthin-treated groups. Furthermore, pre- and post-treatment of astaxanthin showed a higher expression of p-Akt, p-mTOR, Nrf2 and superoxide dismutase activity, and a lower expression of cleaved caspase-3, suggesting anti-apoptotic and anti-oxidative roles. Our findings indicate that astaxanthin can preserve visual function and reduce RGC apoptosis after ischemic insults. Including astaxanthin in daily diet as a supplement may be beneficiary for ischemic optic neuropathy.

To investigate the effect of oroxylin A on the survival of retinal ganglion cells (RGC) and the activation of microglial cells in a rat optic nerve (ON) crush model.Oroxylin A (15mg/Kg in 0.2ml phosphate-buffered saline) or phosphate-buffered saline (PBS control) was immediately administered after ON crush once by subcutaneous injection. Rats were euthanized at 2 weeks after the crush injury. The density of RGC was counted by retrograde labeling with FluoroGold and immunostaining of retina flat mounts for Brn3a. Electrophysiological visual function was assessed by flash visual evoked potentials (FVEP). TUNEL assay, immunoblotting analysis of glial fibrillary acidic protein (GFAP), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the retinas, and immunohistochemistry of GFAP in the retinas and ED1 in the ON were evaluated.Two weeks after the insult, the oroxylin A-treated group had significantly higher FG labeled cells and Brn3a+ cells suggesting preserved RGC density in the central and mid-peripheral retinas compared with those of the PBS-treated group. FVEP measurements showed a significantly better preserved latency of the P1 wave in the ON-crushed, oroxylin A-treated rats than the ON-crushed, PBS treated rats. TUNEL assays showed fewer TUNEL positive cells in the ON-crushed, oroxylin A-treated rats. The number of ED1 positive cells was reduced at the lesion site of the optic nerve in the ON-crushed, oroxylin A-treated group. Increased GFAP expression in the retina was reduced greatly in ON-crushed, oroxylin A-treated group. Furthermore, administration of oroxylin A significantly attenuated ON crush insult-induced iNOS and COX-2 expression in the retinas.These results demonstrated that oroxylin A hasss neuroprotective effects on RGC survival with preserved visual function and a decrease in microglial infiltration in the ONs after ON crush injury.