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Clemens A. Lange, Freya M. Mowat, Ulrich F. Luhmann, Haroon H. Sayed, Peter Kelly, Alexander J. Smith, James Leipner, Robin R. Ali, James W. Bainbridge; Ddah-2 Deletion Promotes Vascular Regeneration In Retinal Ischemia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3122.
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Retinal ischemia and pathological angiogenesis is a central feature of common blinding disorders including retinal vascular occlusive disease and diabetic retinopathy. Nitric oxide (NO) is a potent vasodilator and has pro-angiogenic properties in the retina and choroid. Dimethylarginine dimethylaminohydrolase 2 (DDAH2) is a key regulator of nitric oxide synthases and NO production. The aim of this study was to investigate the role of DDAH2 in physiological and pathological angiogenesis in the retina and choroid.
We assessed the vascular phenotype of DDAH2-knockout mice by in vivo fluorescein angiography and by immuno-histochemistry, and the retinal function by electroretinogram. We investigated the role of DDAH2 in pathological retinal and choroidal angiogenesis using the oxygen-induced retinopathy (OIR) and the laser-induced choroidal neovascularisation mouse model.
DDAH2 deletion had no evident effect on normal retinal vasculature nor on retinal function. In the OIR model we found that DDAH2 deletion reduces the area of ischemia by 59% (±30%, p<0.0001) and the area of preretinal pathological neovascularisation by 71% (±9%, p<0.0001) compared with wild type littermates at P17. We observed no significant difference in laser induced choroidal neovascularisation in DDAH2 deficient mice compared with wild type controls (p=0.17).
DDAH2 has an important role in retinal vascular repair and in the development of ischemia-induced retinal neovascularisation. These results suggest that inhibition of DDAH-2 may offer a safe and efficient therapeutic strategy for retinal ischemia and pathological retinal neovascularisation.
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