RGD Reference Report - Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. - Rat Genome Database

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Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury.

Authors: Nishijima, K  Ng, YS  Zhong, L  Bradley, J  Schubert, W  Jo, N  Akita, J  Samuelsson, SJ  Robinson, GS  Adamis, AP  Shima, DT 
Citation: Nishijima K, etal., Am J Pathol. 2007 Jul;171(1):53-67.
RGD ID: 7421609
Pubmed: PMID:17591953   (View Abstract at PubMed)
PMCID: PMC1941589   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2007.061237   (Journal Full-text)

Vascular endothelial growth factor-A (VEGF-A) has recently been recognized as an important neuroprotectant in the central nervous system. Given its position as an anti-angiogenic target in the treatment of human diseases, understanding the extent of VEGF's role in neural cell survival is paramount. Here, we used a model of ischemia-reperfusion injury and found that VEGF-A exposure resulted in a dose-dependent reduction in retinal neuron apoptosis. Although mechanistic studies suggested that VEGF-A-induced volumetric blood flow to the retina may be partially responsible for the neuroprotection, ex vivo retinal culture demonstrated a direct neuroprotective effect for VEGF-A. VEGF receptor-2 (VEGFR2) expression was detected in several neuronal cell layers of the retina, and functional analyses showed that VEGFR2 was involved in retinal neuroprotection. VEGF-A was also shown to be involved in the adaptive response to retinal ischemia. Ischemic preconditioning 24 hours before ischemia-reperfusion injury increased VEGF-A levels and substantially decreased the number of apoptotic retinal cells. The protective effect of ischemic preconditioning was reversed after VEGF-A inhibition. Finally, chronic inhibition of VEGF-A function in normal adult animals led to a significant loss of retinal ganglion cells yet had no observable effect on several vascular parameters. These findings have implications for both neural pathologies and ocular vascular diseases, such as diabetic retinopathy and age-related macular degeneration.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Retina Reperfusion Injury  ISOVegfa (Rattus norvegicus)7421609; 7421609 RGD 
Retina Reperfusion Injury  IDA 7421609 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neuron apoptotic process  IMP 7421609 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
VEGFA  (vascular endothelial growth factor A)


Additional Information