RGD Reference Report - EDG receptors as a potential therapeutic target in retinal ischemia-reperfusion injury. - Rat Genome Database

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EDG receptors as a potential therapeutic target in retinal ischemia-reperfusion injury.

Authors: Savitz, SI  Dhallu, MS  Malhotra, S  Mammis, A  Ocava, LC  Rosenbaum, PS  Rosenbaum, DM 
Citation: Savitz SI, etal., Brain Res. 2006 Nov 6;1118(1):168-75. Epub 2006 Oct 5.
RGD ID: 2317696
Pubmed: PMID:17026968   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2006.05.060   (Journal Full-text)

LPA (lysophosphatidic acid) specific endothelial differentiation gene (EDG) receptors have been implicated in various anti-apoptotic pathways. Ischemia of the brain and retina causes neuronal apoptosis, which raises the possibility that EDG receptors participate in anti-apoptotic signaling in ischemic injury. We examined the expression of EDG receptors in a model of retinal ischemia-reperfusion injury and also tested LXR-1035, a novel analogue of LPA, in the rat following global retinal ischemic injury. Rats were subjected to 45 or 60 min of raised intraocular pressure. Animals were sacrificed at 24 h post-ischemia and retinal tissue was stained for EDG receptors. In separate experiments, animals were randomized to receive LXR or saline vehicle by intravitreal injection 24 h prior to ischemia. The degree of retinal damage was assessed morphologically by measuring the thickness of the inner retinal layers as well as functionally by electroretinography (ERG). We found that the normal retina has a baseline expression of the LPA receptors, EDG-2 and EDG-4, which are significantly upregulated in the inner layers in response to ischemia. Animals pretreated with LXR-1035 had dose-dependent, significant reductions in histopathologic damage and significant improvement in functional deficits compared with corresponding vehicle-controls, after 45 and 60 min of ischemia. These results suggest that LPA receptor signaling may play an important role in neuroprotection in retinal ischemia-reperfusion injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Retina Reperfusion Injury  ISOLpar1 (Rattus norvegicus)2317696; 2317696protein:increased expression:retinal inner nuclear layer and retinal ganglion cell layer (rat)RGD 
Retina Reperfusion Injury  IEP 2317696protein:increased expression:retinaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Lpar1  (lysophosphatidic acid receptor 1)

Genes (Mus musculus)
Lpar1  (lysophosphatidic acid receptor 1)

Genes (Homo sapiens)
LPAR1  (lysophosphatidic acid receptor 1)

Objects referenced in this article
Gene BUD31 BUD31 homolog Homo sapiens
Gene Bud31 BUD31 homolog Mus musculus

Additional Information