RGD Reference Report - Increased optic atrophy type 1 expression protects retinal ganglion cells in a mouse model of glaucoma. - Rat Genome Database

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Increased optic atrophy type 1 expression protects retinal ganglion cells in a mouse model of glaucoma.

Authors: Ju, WK  Kim, KY  Duong-Polk, KX  Lindsey, JD  Ellisman, MH  Weinreb, RN 
Citation: Ju WK, etal., Mol Vis. 2010 Jul 15;16:1331-42.
RGD ID: 7800720
Pubmed: PMID:20664796   (View Abstract at PubMed)
PMCID: PMC2905637   (View Article at PubMed Central)

PURPOSE: The goal of this study is to determine whether increased optic atrophy type 1 (OPA1) expression protects against retinal ganglion cell (RGC) death in glaucomatous DBA/2J mice. METHODS: Intraocular pressure in DBA/2J mice was measured, and pre-glaucomatous DBA/2J mice eyes were transfected with recombinant adeno-associated virus serotype 2 (AAV2) constructs including AAV2-wild type (WT) mOPA1 for two months. Increased OPA1 expression was confirmed by western blotting and RGC survival was assessed by retrograde labeling with FluoroGold. In addition, apoptotic cell death and mitochondrial structure were determined in AAV2-WT mOPA1-transfected differentiated RGC-5 cells exposed to elevated hydrostatic pressure (30 mmHg) for three days. RESULTS: WT AAV2-mOPA1 transfection significantly increased 90 kDa and 80 kDa OPA1 isoforms in the retina of glaucomatous DBA/2J mice. OPA1 immunoreactivity was increased in the inner nuclear layer, inner plexiform layer, and ganglion cell layer in nine month-old glaucomatous DBA/2J mice transfected with AAV2-WT mOPA1. Overexpression of OPA1 significantly increased RGC survival at two months after AAV2-WT mOPA1 transfection, and decreased activation of both astroglia and microglia in the retina of glaucomatous DBA/2J mice. Also, overexpression of OPA1 in differentiated RGC-5 cells resulted in less apoptotic cell death and blocked mitochondrial fission following elevated hydrostatic pressure. CONCLUSIONS: OPA1 can directly modulate RGC survival, and increasing OPA1 expression may protect against RGC death in glaucomatous optic neuropathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glaucoma treatmentISOOpa1 (Mus musculus)7800720; 7800720 RGD 
glaucoma treatmentIMP 7800720 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Opa1  (OPA1, mitochondrial dynamin like GTPase)

Genes (Mus musculus)
Opa1  (OPA1, mitochondrial dynamin like GTPase)

Genes (Homo sapiens)
OPA1  (OPA1 mitochondrial dynamin like GTPase)


Additional Information