Diabetes, Ocular Diabetes, and Galactosemia：糖尿病，糖尿病和半乳糖血症的眼，.ppt

There are 5 biochemical hypotheses that offer explanations to the cause of blood vessel loss in diabetic retinopathy: the osmotic effect of polyol formation (in the pericytes). ? in diacylglycerol that causes the synthesis of endothelin-1 ? in mitogen activated protein kinase that ? endothelin-1 glycation of proteins (affecting vessel collagens) oxidation that also ? glycation of proteins Hypothesis 1: The polyol pathway…Although the polyol pathway no longer seemed to be an attractive mechanism for diabetic retinopathy a few years back, new evidence suggests that it now may be so. What is lacking is an ARI (aldose reductase inhibitor) that is effective. It is quite clear that AR and the polyol pathway operate in both blood vessel endothelial cells and pericytes in the retina. It is also thought that the pathway exists in Müller cells that support the neural retinal photoreceptors. One investigator has stated that the presently available ARIs were not strong enough and when boosted would protect against cellular damage in the retina if only the well-known side effects of these agents could be prevented. So the future in prevented diabetic retinopathy may lie in the discovery of a safe inhibitor. Hypothesis 2: diacylglycerol and endothelin-1….An intermediate offshoot from the E-M pathway is a 3-carbon compound esterified to fatty acids called diacyglycerol. This substance activates protein kinase C which, in turn, brings about a gene induction for the synthesis of the protein endothelin-1 (see pp. 118-119 in your text). Endothelin-1 promotes blood vessel occlusion (blockage). Since pericytes have receptors for endothelin-1, it is possible that this peptide may induce blood vessel blockage only leading to leakiness as a secondary effect. Hypothesis 3: MAP kinase and endothelin-1….This is a variation of hypotheis 2 in which mitogen stimulated protein kinase (MAP kinase) also stimulates the synthesis of endothelin-1. The stimulation of MAP kinase activity has b