RGD Reference Report - SDF-1 is both necessary and sufficient to promote proliferative retinopathy. - Rat Genome Database

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SDF-1 is both necessary and sufficient to promote proliferative retinopathy.

Authors: Butler, JM  Guthrie, SM  Koc, M  Afzal, A  Caballero, S  Brooks, HL  Mames, RN  Segal, MS  Grant, MB  Scott, EW 
Citation: Butler JM, etal., J Clin Invest. 2005 Jan;115(1):86-93.
RGD ID: 2306559
Pubmed: PMID:15630447   (View Abstract at PubMed)
PMCID: PMC539202   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI22869   (Journal Full-text)

Diabetic retinopathy is the leading cause of blindness in working-age adults. It is caused by oxygen starvation in the retina inducing aberrant formation of blood vessels that destroy retinal architecture. In humans, vitreal stromal cell-derived factor-1 (SDF-1) concentration increases as proliferative diabetic retinopathy progresses. Treatment of patients with triamcinolone decreases SDF-1 levels in the vitreous, with marked disease improvement. SDF-1 induces human retinal endothelial cells to increase expression of VCAM-1, a receptor for very late antigen-4 found on many hematopoietic progenitors, and reduce tight cellular junctions by reducing occludin expression. Both changes would serve to recruit hematopoietic and endothelial progenitor cells along an SDF-1 gradient. We have shown, using a murine model of proliferative adult retinopathy, that the majority of new vessels formed in response to oxygen starvation originate from hematopoietic stem cell-derived endothelial progenitor cells. We now show that the levels of SDF-1 found in patients with proliferative retinopathy induce retinopathy in our murine model. Intravitreal injection of blocking antibodies to SDF-1 prevented retinal neovascularization in our murine model, even in the presence of exogenous VEGF. Together, these data demonstrate that SDF-1 plays a major role in proliferative retinopathy and may be an ideal target for the prevention of proliferative retinopathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetic retinopathy severityIEP 2306559protein:increased expression:vitreous humorRGD 
diabetic retinopathy severityISOCXCL12 (Homo sapiens)2306559; 2306559protein:increased expression:vitreous humorRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcl12  (C-X-C motif chemokine ligand 12)

Genes (Mus musculus)
Cxcl12  (C-X-C motif chemokine ligand 12)

Genes (Homo sapiens)
CXCL12  (C-X-C motif chemokine ligand 12)


Additional Information