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Am J Transl Res. 2016 Feb 15;8(2):799-810. eCollection 2016.

Adeno-associated virus mediated SOD gene therapy protects the retinal ganglion cells from chronic intraocular pressure elevation induced injury via attenuating oxidative stress and improving mitochondrial dysfunction in a rat model.

Author information

1
Department of Ophthalmology, Second Xiangya Hospital, Central South University Changsha 410011, Hunan, China.

Abstract

PURPOSE:

This study aimed to determine whether chronic intraocular pressure (IOP) elevation induces retinal oxidative stress and alters mitochondrial morphology and function of retinal ganglion cells (RGC) and to explore the effects of AAV-SOD2 gene therapy on the RGC survival and mitochondrial dysfunction.

METHODS:

Chronic experimental glaucoma was induced unilaterally in adult male Sprague-Dawley rats by laser burns at trabecular meshwork and episcleral veins 2 times with an interval of one week. One eye of each rat was intravitreally pretreated with recombinant adeno-associated virus expressing SOD2 (AAV-SOD2) or recombinant AAV expressing GFP (AAV-GFP) 21 days before glaucoma induction. RGCs counting, morphometric analysis of retina and optic nerve, and detection of activities of retinal SOD2 and catalase, MDA, mitochondrial morphology, mitochondrial dynamin protein OPA1 and DRP-1 expressions were conducted at 4, 8, 12 and 24 weeks.

RESULTS:

Severe RGC loss, degeneration of optic nerve, reduced thickness of RGC layer and nerve fiber layer, significant decrease in total SOD and catalase activities, mitochondrial dysfunction and increased MDA were observed at 4, 8, 12 and 24 weeks after glaucoma. Pretreatment with AAV-SOD2 significantly reduced MDA and attenuated the damage to RGCs through a mitochondria-related pathway.

CONCLUSION:

AAV mediated pre-treatment with SOD2 is able to attenuate oxidative stress and improve mitochondrial dysfunction of RGC and optic nerve secondary to glaucoma. Thus, SOD2 may be used to prevent the retinal RGCs from glaucoma, which provides a promising strategy for glaucoma therapy.

KEYWORDS:

Chronic intraocular pressure; SOD; retinal ganglion cells

PMID:
27158370
PMCID:
PMC4846927

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