Molecular biological analysis and treatment for diabetic retinopathy

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Diabetic retinopathy is a major cause of blindness in adults. We investigate the retinal changes in SDT (Spontaneously Diabetic Torii) rats, a model of type 2 diabetic mellitus, and the molecular mechanisms controlling the diabetic retinopathy. Propliferative tissues that are similar to human proliferative diabetic retinopathy (PDR) are found in eyes of some of the SDT rats. However, SDT rats have a low incidence of retinal neovascularization and poor development of retinal non-perfused areas. Expression of vascular endothelial growth factor (VEGF), a major angiogenic stimulator, and pigment epithelium-derived factor (PEDF), an angiogenic inhibitor, were both increased in the retina of SDT rats. PEDF inhibited the VEGF-induced leukostasis. Thus, the high levels of PEDF in the retina of SDT rats may contribute to the low incidence of neovascular formation and absence of non-perfused areas that did not match the typical diabetic retinopathy in humans. In human PDR tissues, VEGF and PEDF were both strongly expressed, but the distribution was different.Platelet-derived microparticles (PDMPs) stimulate the coagulation cascade and increase leukocyte and endothelial cell adhesions, and monocytes-derived microparticles (MDMPs) are released from activated monocytes and enhance the procoagulant activity. These activities are key events in the development of diabetic retinopathy. PDMPs and MDMPs are correlated with each other and also correlated with activated platelet (CD62P and CD63) and adhesion molecules (P-selectin and ICAM-1). PDMPs and MDMPs are increased according to the progression of diabetic retinopathy. Therefore, increased levels of MDMPs and PDMPs may accelerate the progression of diabetic retinopathy.