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Updated: Jun 26, 2026
A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure
Published on: July 14, 2016
SIRT4 Alleviates Retinal Ischemia-Reperfusion Injury Via Mediating Astrocytes Lipid Metabolism and Mitochondrial
Hongdou Luo1, Ming Jin1,2,3, Ke Xu1
1Affiliated Eye Hospital of Nanchang University, Jiangxi Research Institute of Ophthalmology and Visual Science, Jiangxi Provincial Key Laboratory for Ophthalmology, Jiangxi Clinical Research Center for Ophthalmic Disease, Nanchang, China.
Purpose:
To investigate whether SIRT4 protects the optic nerve by regulating mitochondrial function and lipid metabolism in neurotoxic reactive astrocytes in the retinal ischemia-reperfusion injury.
Methods:
Using SIRT4 knockout, wild-type, and overexpressing mouse ischemia-reperfusion (I/R) models, we assessed retinal ganglion cell loss, protein expression (SIRT4, APOL6, GBP2, mitochondrial dynamics), and conducted metabolomic/transcriptomic analyses. In vitro, primary astrocytes were treated with TIC cytokines; SIRT4 was knocked down via lentivirus, followed by measurement of ATP, lipid secretion, and mitochondrial morphology/function.
Results:
SIRT4 was highly expressed in astrocytes. Its knockdown exacerbated I/R injury, promoting a neurotoxic astrocyte phenotype with increased APOL6 expression, and elevated secretion of long-chain fatty acids and phosphatidylcholines and mitochondrial damage. SIRT4 deficiency enhanced astrocyte susceptibility to injury, further reducing ATP production and worsening lipid accumulation and optic nerve damage.
Conclusions:
SIRT4 plays a protective role in retinal ischemia-reperfusion injury model by regulating astrocyte lipid metabolism and mitochondrial function, offering a potential therapeutic target for neuroprotection.