RGD Reference Report - Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathy. - Rat Genome Database

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Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathy.

Authors: Yoshida, Y  Yamagishi, S  Matsui, T  Jinnouchi, Y  Fukami, K  Imaizumi, T  Yamakawa, R 
Citation: Yoshida Y, etal., Diabetes Metab Res Rev. 2009 Oct;25(7):678-86.
RGD ID: 2317854
Pubmed: PMID:19685553   (View Abstract at PubMed)
DOI: DOI:10.1002/dmrr.1007   (Journal Full-text)

BACKGROUND: Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy. METHODS: Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)-conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence. RESULTS: Retinal PEDF levels were reduced, and amplitudes of a- and b-wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Muller cells. Further, retinal 8-OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy. CONCLUSIONS: Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase-driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CYBAHumandiabetic retinopathy  ISOCyba (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 
CybaRatdiabetic retinopathy  IEP associated with Diabetes Mellitus and ExperimentalRGD 
CybaMousediabetic retinopathy  ISOCyba (Rattus norvegicus)associated with Diabetes Mellitus and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyba  (cytochrome b-245 alpha chain)

Genes (Mus musculus)
Cyba  (cytochrome b-245, alpha polypeptide)

Genes (Homo sapiens)
CYBA  (cytochrome b-245 alpha chain)


Additional Information