losartan-potassium and Choroid-Neoplasms

Ocular vascular diseases such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration, whose population increases along with aging, have become leading causes of severe visual disturbance. Macular edema and serous retinal detachment are associated with abnormal vascular leakage and tractional retinal detachment, and neovascular glaucoma is caused by retinal neovascularization. Such ocular vascular diseases are caused by vascular cell aging and vascular damage associated with lifestyle-related diseases including diabetes mellitus, hypertension, hyperlipidemia, and obesity. In the present study, we investigated molecular mechanisms in such vascular deficiencies using vascular cell biology methodology, and we propose novel strategies for the treatment of such vascular diseases. Along with aging, oxidative stress and physical stress, such as mechanical stretch, continuously and directly insult vascular cells. Such stress induces apoptosis by intracellular signaling through stress kinases in cultured retinal vascular cells. Inhibition of such stress kinases could be an effective treatment to protect the vascular cells against age-related damage. In a retinal vascular developmental model, pericyte loss causes pathology mimicking macular edema and proliferative diabetic retinopathy. Angiopoietin 1 (Ang 1) secreted by pericytes suppresses oxidative stress-induced intracellular signaling through stress kinases linked to cell apoptosis and normalizes such retinal pathology. This suggests that the paracrine action of Ang 1 in the pericytes is necessary to sustain normal retinal vasculature, and that Ang 1-triggered intracellular signaling is useful for the treatment of vascular cell pathology associated with pericyte loss. In diabetic retinopathy and retinal vein occlusion, retinal vessels regress along with retinal vascular cell apoptosis, and the retina becomes ischemic followed by pathological retinal neovascularization. VEGF has been recognized as a predominant factor to induce the ischemic retinal neovascularization. We found that retinal vascular cells have a characteristic pattern in VEGF receptor expression, which causes vascular pathology more frequently in the retina than in other organs. Neuropilin 1 (NRP 1), which enhances VEGF receptor function, is abundantly expressed in the retinal endothelial cells and is upregulated by VEGF itself and by hypoxia to regulate a positive feedback mechanism in retinal neovascularization. Th

Topics: Aging; Angiogenesis Inhibitors; Angiopoietin-1; Angiotensin II Type 1 Receptor Blockers; Animals; Apoptosis; Choroid Neoplasms; Diabetic Retinopathy; Drug Design; Erythropoietin; Humans; Life Style; Neuropilin-1; Oxidative Stress; Pericytes; Renin-Angiotensin System; Retinal Vein Occlusion; Signal Transduction; Vascular Endothelial Growth Factor A