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Doaa Sobeih, Khaled Hussein, Neveen Said, Kouros Motamed, Mohamed Al-Shabrawey; Effect of SPARC deletion on retinal neovascularization and capillary drop out in mouse model of ischemic retinopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):376.
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© ARVO (1962-2015); The Authors (2016-present)
: The matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC/osteonectin) has been shown to play an important role in pathological angiogenesis. Previous animal studies have also supported the concept of SPARC as an angiogenesis regulator in some retinal diseases such as choroidal neovascularization (CNV) as well as proliferative diabetic retinopathy (PDR). However, the exact role of SPARC in regulation of the angiogenesis process is still unclear. The aim of the current study was to investigate the effect of the matricellular SPARC deletion on pathological angiogenesis and capillary drop out in the mouse model of oxygen induced retinopathy (OIR).
Whole-mount retinas labeled with vascular marker (Isolectin-B4) were examined in OIR wild type (n=7) and OIR SPARC-deficient mice (n=7). Analysis was performed at postnatal day 17 (P17) after they were exposed to 77% Oxygen for five days (P7- P12), followed by exposing the animal to normal air for 5 days until P17. Analysis of retinal vasculatures in retinal flat mounts included the total area of new capillary tufts and area of capillary dropout normalized to the total retinal area. Using Western Blot (WB), SPARC expression was analyzed in retinal homogenates of OIR wild type mice (P14 and P17) versus control mice at same time points. Human retinal endothelial cells (HRECs) were exposed to low oxygen treatment (1%) for 6 hrs before measuring the levels of SPARC by WB.
We noticed a modest increase in the new capillary tufts in SPARC-deficient mice, compared to the wild type. However, lack of SPARC was associated with significant increase in the capillary dropout in comparison with the wild type (p value=0.03).Meanwhile, a significant decrease in the SPARC protein levels were detected by WB performed on the retinas of OIR wild type animal model compared to the control animals at P14 (p value=0.01) while no significant difference was noticed at P17. Moreover, hypoxia significantly abrogated SPARC expression in HRECs.
SPARC deletion augments the severity of ischemic retinopathy in the form of increasing capillary drop out areas with modest increase in pathological neovascularization. Therefore, modulation of SPARC expression in retina could be a novel therapeutic approach to prevent pathological retinal neovascularization
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