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Kana Sase, Yasushi Kitaoka, Yasunari Munemasa, Hitoshi Takagi; Atg4A in axonal protection by short-term hyperglycemia in TNF-induced optic nerve degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5065.
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We have recently showed that short-term hyperglycemia protects axons in TNF-induced optic nerve degeneration and that this axonal-protective effect may be associated with autophagy machinery. In this study, we investigated the expression of autophagy-related genes 4A (Atg4A) in this axon process.
Wistar rats were divided into two group. One group remained normoglycemia (NG), the other was rendered hyperglycemia (HG) by an intraperitoneal injection of streptozotocin (STZ). In both groups, TNF was administered intravitreally into the right eyes. PBS alone was administered into the left eyes as a control. In the HG group, 3-methyladenine (3-MA) was also administered simultaneously with TNF into the right eyes. One week after intravitreal injection, Western blot analysis and immunostaining were performed to investigate the Atg4A expression in optic nerve.
Western blot analysis showed the existence of Atg4A in optic nerve. The protein level of Atg4A was significantly increased in optic nerve in TNF-treated eyes compared with that in PBS-treated eyes. The short-term HG did not significantly alter the Atg4A protein levels in optic nerve.Treatment of 3-MA did not alter the Atg4A protein levels in optic nerve in HG groups. Immunohistochemical study showed that Atg4A was colocalized with GFAP but not neurofilament.
Although we previously observed that LC3 (Atg8) exists inside axon and is involved in the short-term HG axonal protection, the present results suggest that enhanced glial Atg4A may be involved in TNF-induced optic nerve degeneration but not in HG axonal protection.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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