RGD Reference Report - Early inner retinal astrocyte dysfunction during diabetes and development of hypoxia, retinal stress, and neuronal functional loss. - Rat Genome Database

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Early inner retinal astrocyte dysfunction during diabetes and development of hypoxia, retinal stress, and neuronal functional loss.

Authors: Ly, A  Yee, P  Vessey, KA  Phipps, JA  Jobling, AI  Fletcher, EL 
Citation: Ly A, etal., Invest Ophthalmol Vis Sci. 2011 Dec 2;52(13):9316-26. doi: 10.1167/iovs.11-7879.
RGD ID: 7364887
Pubmed: PMID:22110070   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.11-7879   (Journal Full-text)

PURPOSE: Neuronal and glial alterations precede the overt vascular change that characterizes diabetic retinopathy. Because retinal astrocytes modulate neuronal and vascular function, this study investigated the time course of astrocyte, Muller cell, and neuronal change during diabetes to determine whether astrocytes may play an early role in diabetic retinopathy. METHODS: Sprague-Dawley rats were rendered diabetic via streptozotocin and neuronal and glial changes were assessed after 2-10 weeks. Astrocyte change was investigated using connexin-26 immunolabeling, whereas connexin-26 and -43 gene expressions were quantified using real-time PCR. Hypoxia was measured by pimonidazole labeling and the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) was quantified using Western blot. Muller cell gliosis was assessed by glial fibrillary acidic protein immunolabeling and retinal function assessed using the electroretinogram. RESULTS: Astrocyte connexin-26 and -43 gene and protein expression decreased after 4 weeks of diabetes, before significant astrocyte loss. At the same time, the retina became hypoxic, with increased HIF-1alpha expression and pimonidazole labeling in the ganglion cell layer. This coincided with a decrease in ganglion cell function. After 6 weeks of diabetes, Muller cell gliosis became more evident and there were additional functional deficits in photoreceptoral and amacrine cell responses. CONCLUSIONS: These findings suggest that early changes in astrocytes are coincident with inner retinal hypoxia and ganglion cell functional deficits, whereas Muller cell gliosis and more extensive decreases in neuronal function occur later. Astrocytes may play an early and key role in changes in retinal vasculature and inner retinal dysfunction in diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetic retinopathy  ISOHif1a (Rattus norvegicus)7364887; 7364887associated with Diabetes Mellitus more ...RGD 
diabetic retinopathy  IEP 7364887associated with Diabetes Mellitus more ...RGD 
Experimental Diabetes Mellitus  ISOGja1 (Rattus norvegicus)7364887; 7364887protein:altered expression:retina:RGD 
Experimental Diabetes Mellitus  ISOGjb2 (Rattus norvegicus)7364887; 7364887mRNA and protein:decreased expression:retina:RGD 
Experimental Diabetes Mellitus  IEP 7364887protein:altered expression:retina:RGD 
Experimental Diabetes Mellitus  IEP 7364887mRNA and protein:decreased expression:retina:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gja1  (gap junction protein, alpha 1)
Gjb2  (gap junction protein, beta 2)
Hif1a  (hypoxia inducible factor 1 subunit alpha)

Genes (Mus musculus)
Gja1  (gap junction protein, alpha 1)
Gjb2  (gap junction protein, beta 2)
Hif1a  (hypoxia inducible factor 1, alpha subunit)

Genes (Homo sapiens)
GJA1  (gap junction protein alpha 1)
GJB2  (gap junction protein beta 2)
HIF1A  (hypoxia inducible factor 1 subunit alpha)


Additional Information