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Sankarathi Balaiya, Maria Grant, K V Chalam; Growth Factors/Cytokines Present In Diabetic Vitreous Inhibit CD34+ Bone Marrow Derived Stem Cell Function. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1354.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic dysfunctional CD34+ cells play an important role in proliferative diabetic retinopathy (PDR). This study was undertaken to evaluate the role of growth factors/cytokines in human PDR vitreous on bone marrow derived CD34+ cells.
Fresh human CD34+ cells from healthy individuals were treated with human PDR vitreous and control samples (no PDR; after obtaining IRB approval) overnight in a CO2 incubator at 37C. The conditioned mixture was collected and their angiogenic role was analyzed using human retinal microvascular endothelial cells (HRMEC) by in vitro angiogenic assay. Presence of angiogenic cytokines were measured using angiogenic antibody array. Their expression levels were compared against the control vitreous samples treated conditioned mixture.
In HRMEC, PDR vitreous treated conditioned mixture showed reduced number of tubes (66±2.1, p<0.05) compared to control vitreous treated conditioned mixture (80±2.5). We observed a total of seven angiogenic proteins in the CD34+ cells treated with vitreous samples (conditioned mixture). Two of the proteins (CXCL4, SerpinF1) were upregulated in PDR vitreous treated CD34+ cell conditioned mixture (p<0.01). Three other proteins (Thrombospondin-1, dipeptidylpeptidase IV and angiopoietin-2, were present only in PDR vitreous treated CD34+ cell conditioned mixture. Other two proteins (endothelin-1 and tissue inhibitor of metalloproteinases-1) were equally present in both PDR vitreous and control vitreous treated CD34+ cell conditioned mixture.
Presence of angiogenic proteins such as CXCL4 and dipeptidylpeptidase IV in vitreous are responsible for CD34+ mobilization for vascular repair in diabetic retinopathy.
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