• Ahmed M Abu El-Asrar, Ajmal Ahmad, Kaiser Alam, Mohammad Mairaj Siddiquei, Ghulam Mohammad, HertoghGert DeGLaboratory of Histochemistry and Cytochemistry, University of Leuven, KU Leuven, Leuven, Belgium., Ahmed Mousa, and Ghislain Opdenakker.
• Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
• Acta Ophthalmol. 2017 Nov 1; 95 (7): 697-704.

PurposeExtracellular matrix metalloproteinase inducer (EMMPRIN) promotes angiogenesis through matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) production. We investigated the expression levels of EMMPRIN and correlated these levels with VEGF, MMP-1 and MMP-9 in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of EMMPRIN in the retinas of diabetic rats and the effect of EMMPRIN on the induction of angiogenesis regulatory factors in human retinal microvascular endothelial cells (HRMECs).MethodsVitreous samples from 40 PDR and 19 non-diabetic patients, epiretinal membranes from 12 patients with PDR, retinas of rats and HRMECs were studied by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, Western blot analysis, zymography analysis and RT-PCR.ResultsWe showed a significant increase in the expression of EMMPRIN, VEGF, MMP-1 and MMP-9 in vitreous samples from PDR patients compared with non-diabetic controls (p < 0.0001; p = 0.001; p = 0.009; p < 0.0001, respectively). Significant positive correlations were found between the levels of EMMPRIN and the levels of VEGF (r = 0.38; p = 0.003), MMP-1 (r = 0.36; p = 0.005) and MMP-9 (r = 0.46; p = 0.003). In epiretinal membranes, EMMPRIN was expressed in vascular endothelial cells and stromal cells. Significant increase of EMMPRIN mRNA was detected in rat retinas after induction of diabetes. EMMPRIN induced hypoxia-inducible factor-1α, VEGF and MMP-1 expression in HRMEC.ConclusionsThese results suggest that EMMPRIN/MMPs/VEGF pathway is involved in PDR angiogenesis.© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

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