Research ArticleNeovascularization

SOCS3 in retinal neurons and glial cells suppresses VEGF signaling to prevent pathological neovascular growth

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Science Signaling  22 Sep 2015:
Vol. 8, Issue 395, pp. ra94
DOI: 10.1126/scisignal.aaa8695

Halting blood vessel formation in the eye

Diabetics and preterm infants are susceptible to vision loss or blindness because of abnormal blood vessel formation in the eye, a process called retinal neovascularization. Using a model of this disease process, Sun et al. found that mice that lacked a protein called SOCS3 in the neurons and glial cells of the eye had greater retinal neovascularization than did control mice. Their results suggest that SOCS3 prevents neurons and glial cells from releasing too much VEGF (a cytokine that promotes blood vessel formation) by inhibiting the transcription factor STAT3, which can trigger the production of VEGF.


Neurons and glial cells in the retina contribute to neovascularization, or the formation of abnormal new blood vessels, in proliferative retinopathy, a condition that can lead to vision loss or blindness. We identified a mechanism by which suppressor of cytokine signaling 3 (SOCS3) in neurons and glial cells prevents neovascularization. We found that Socs3 expression was increased in the retinal ganglion cell and inner nuclear layers after oxygen-induced retinopathy. Mice with Socs3 deficiency in neuronal and glial cells had substantially reduced vaso-obliterated retinal areas and increased pathological retinal neovascularization in response to oxygen-induced retinopathy, suggesting that loss of neuronal/glial SOCS3 increased both retinal vascular regrowth and pathological neovascularization. Furthermore, retinal expression of Vegfa (which encodes vascular endothelial growth factor A) was higher in these mice than in Socs3 flox/flox controls, indicating that neuronal and glial SOCS3 suppressed Vegfa expression during pathological conditions. Lack of neuronal and glial SOCS3 resulted in greater phosphorylation and activation of STAT3, which led to increased expression of its gene target Vegfa, and increased endothelial cell proliferation. In summary, SOCS3 in neurons and glial cells inhibited the STAT3-mediated secretion of VEGF from these cells, which suppresses endothelial cell activation, resulting in decreased endothelial cell proliferation and angiogenesis. These results suggest that neuronal and glial cell SOCS3 limits pathological retinal angiogenesis by suppressing VEGF signaling.

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