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

Jason M. Butler, Steven M. Guthrie, Mehmet Koc, Aqeela Afzal, Sergio Caballero, H. Logan Brooks, Robert N. Mames, Mark S. Segal, Maria B. Grant, Edward W. Scott

Research output: Contribution to journalArticle

217 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)86-93
Number of pages8
JournalJournal of Clinical Investigation
Volume115
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Butler, J. M., Guthrie, S. M., Koc, M., Afzal, A., Caballero, S., Brooks, H. L., Mames, R. N., Segal, M. S., Grant, M. B., & Scott, E. W. (2005). SDF-1 is both necessary and sufficient to promote proliferative retinopathy. Journal of Clinical Investigation, 115(1), 86-93. https://doi.org/10.1172/JCI200522869