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

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.

Proliferative Diabetic Retinopathy: An Overview of Vitreous Immune and Biomarkers

“…It recruits endothelial progenitor cells (EPCs) from the bone marrow to the site of repair and upregulates expression of VEGF, increasing the angiogenic process. This pro-angiogenic factor is categorized as being hypoxia-responsive and is found to be upregulated in PDR [98][99][100] …”

Second line therapy in type 2 diabetes: legacy effect activation

“…Потенциал воздействия иДПП-4 на течение ДР обусловлен наличием у этой группы препаратов большого числа суб-стратов, помимо ГПП-1. Одним из таких субстратов явля-ется stromalcell-derivedfactor-1 alpha (SDF-1a), отвечающий за ангиогенез [16]. Этот хемокин провоцирует ангиогенез, а концентрация SDF-1a увеличивается при пролифератив-ной ДР.…”

The Multifactorial Nature of Retinal Vascular Disease

“…The pathophysiological role of eicosanoids in the eye is of great interest in ophthalmology because AA metabolites have been implicated in a number of ocular disorders including uveitis, CME and DR [22]. Stromal cell-derived factor-1 (SDF-1), a cytokine involved in cellular trafficking and angiogenesis, may also play a major role in the pathology of both ME and proliferative DR (PDR) [23]. …”