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

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HIF1AHumandiabetic retinopathy  ISORGD:61928associated with Diabetes Mellitus, Experimental;protein:increased expression:retina (rat)RGD 
Hif1aRatdiabetic retinopathy  IEP associated with Diabetes Mellitus, Experimental;protein:increased expression:retina (rat)RGD 
Hif1aMousediabetic retinopathy  ISORGD:61928associated with Diabetes Mellitus, Experimental;protein:increased expression:retina (rat)RGD 
GJA1HumanExperimental Diabetes Mellitus  ISORGD:2690protein:altered expression:retina:RGD 
GJB2HumanExperimental Diabetes Mellitus  ISORGD:728891mRNA,protein:decreased expression:retina:RGD 
Gja1RatExperimental Diabetes Mellitus  IEP protein:altered expression:retina:RGD 
Gja1MouseExperimental Diabetes Mellitus  ISORGD:2690protein:altered expression:retina:RGD 
Gjb2RatExperimental Diabetes Mellitus  IEP mRNA,protein:decreased expression:retina:RGD 
Gjb2MouseExperimental Diabetes Mellitus  ISORGD:728891mRNA,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