Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy.
Curr Med Chem. 2013;20(26):3218-25. doi: 10.2174/09298673113209990022.
The onset of diabetic retinopathy is characterized by morphologic alterations of the microvessels, with thickening of the basement membrane, loss of inter-endothelial tight junctions and early and selective loss of pericytes, together with increased vascular permeability, capillary occlusions, microaneurysms and, later, loss of endothelial cells (EC). A key role in the evolution of the disease is played by pericytes, specialized contractile mesenchymal cells of mesodermal origin, that, in capillaries, exert a function similar to smooth muscle cells in larger vessels, regulating vascular tone and perfusion pressure. Thickening of the basement membrane, together with systemic and local hypertension, hyperglycaemia, advanced glycation end-product formation and hypoxia, may disrupt the tight link between pericytes and EC causing pericyte apoptosis, while endothelium, deprived of proliferation control, can give rise to new vessels. Pericyte dropout has great consequences on capillary remodelling and may cause the first abnormalities of the diabetic eye which can be observed clinically. Hyperglycaemia and local hypertension are known to be a direct cause of pericyte apoptosis and dropout, and intracellular biochemical pathways of the glucose metabolites have been explored. However, the exact mechanisms are not yet fully understood and need further clarification in order to develop new effective drugs for the prevention of retinopathy.
糖尿病性视网膜病变的发病机制以微血管的形态改变为特征，包括基底膜增厚、内皮细胞间紧密连接丧失和周细胞的早期和选择性丢失，同时伴有血管通透性增加、毛细血管闭塞、微动脉瘤，以及随后的内皮细胞丢失。周细胞在疾病的进展中起着关键作用，周细胞是中胚层来源的具有收缩功能的特化间充质细胞，在毛细血管中发挥类似于较大血管中平滑肌细胞的功能，调节血管张力和灌注压。基底膜增厚，加上全身和局部高血压、高血糖、晚期糖基化终产物形成和缺氧，可能破坏周细胞和内皮细胞之间的紧密联系，导致周细胞凋亡，而失去增殖控制的内皮细胞则可能产生新的血管。周细胞丢失对毛细血管重构有很大影响，并可能导致糖尿病患者眼部的最初异常，这些异常可以在临床上观察到。高血糖和局部高血压是周细胞凋亡和丢失的直接原因，已经探索了葡萄糖代谢物的细胞内生化途径。然而，确切的机制尚未完全阐明，需要进一步澄清，以便开发预防视网膜病变的新有效药物。
