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Raquel Formica, Jikui Shen, Christopher P. Seidel, Sean F. Hackett, Michael S. Kramer, Mark L. Lupher Jr., Peter A. Campochiaro; Recombinant Pentraxin-2 (rPTX-2) Shifts Macrophage Phenotype, Suppresses Subretinal NV, and Reduces Associated Vascular Leakage and Collagen Deposition Deposition. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1211.
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Pentraxin-2 (PTX-2) or serum amyloid P (SAP) is a circulating 125 kD member of the pentraxin family and a soluble pattern recognition receptor. We previously showed that rPTX-2 reduces the number of macrophages in the eye and suppresses retinal and choroidal NV. In this study, we tested the effect of rPTX-2 on leakage, collagen deposition, macrophage markers, and expression of mRNA for IL-10.
Leakage from choroidal NV was assessed by fluorescein angiography and collagen deposition was assessed by measurement of the area of Trichrome staining on serial ocular sections through entire NV lesions. Leakage from subretinal NV in rho/VEGF transgenic mice was assessed by immunohistochemical staining for albumin. The level of IL-10 mRNA was measured by quantitative real time RT-PCR. Macrophage populations were assessed by immunofluorescent staining for F4/80, CXCR4, CCR2, and CX3CR1.
Compared to intraocular injection of vehicle after laser-induced rupture of Bruch’s membrane, there was significant reduction in the mean area of NV after injection of 2 (40%), 5 (43%) or 20μg (50%) of rPTX-2, but not 0.2μg. Seven days after rupture of Bruch’s membrane and injection of 2μg of rPTX-2 or vehicle, fluorescein angiography showed reduced fluorescein leakage from choroidal NV in rPTX-2-injected compared to vehicle-injected eyes. Treatment with rPTX-2 also reduced the area of collagen staining associated with choroidal NV lesions. Rhodopsin/VEGF transgenic mice were given intraocular injections of vehicle or 20μg of rPTX-2 at P14 and P17. At P21, the area of albumin staining per retina was 0.0128mm2 in rPTX-2-injected eyes compared to 0.0361mm2 in vehicle injected eyes (p=0.0003). Compared to eyes injected with vehicle, those injected with rPTX-2 had a significant increase in IL10 mRNA. Mice with ischemia-induced retinal NV treated with rPTX-2 had significantly fewer CXCR4+, CCR2+ and F4/80+ cells in the retina compared to controls, but no difference in CX3CR1+ cells.
PTX-2 reduces total macrophage number in ischemic retina and causes a relative increase in CX3CR1+ cells versus those positive for CXCR4, CCR2 and F4/80. This and the increase in IL-10 mRNA suggest an increase in MREG/M1(ratio). This change in macrophage number and phenotype is associated with suppression of NV and reduced leakage and collagen deposition.
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