| Summary: | 碩士 === 國立陽明大學 === 生物藥學研究所 === 94 === Age-related macular degeneration (AMD) causes gradual loss of central vision by damaging the retinal pigment epithelial (RPE) cells. In the present day there haven’t found the correct target for drug development in AMD. By far the therapy can only treat the secondary complications, such as growth of abnormal blood vessels. RPE is critical to the maintenance and normal function of the retina. We hypothesized that there is a potential role for RPE to regenerate retina. We believe that enhance or maintain the RPE cells functions can be the therapy target for AMD. The aim of this study is to find out drugs that can promote RPE functions and further to set up animal models for the evaluation of retina function impairment to establish ophthalmic drugs screening plateform.
We have tested several kinds of Chinese herbal extract that are known to gave enhanced bovine RPE cell phagocytosis activity on the mice RPE cell phagocytosis activity drug screening platform.These Chinese herbal medicine have similar effective pattern in bovine and mice phagocytosis activity drug screening platform. We also find that 0.1, 1, and 10 μg/ml nicotinamide and 0.01, 0.1μg/ml resveratrol also enhance RPE phagocytosis activity. In the in vitro model of CoCl2 induced RPE cell damage 0.1, 1, 10, and 100 μg/ml nicotinamide and 0.1, 1μg/ml resveratrol can increase cell viability about 15%. In RPE proliferation platform 0.1, 1, 10, and100μg/ml nicotinamide and 10 μg/ml resveratrol can inhibit RPE proliferation. In RPE cell migration assay platform 1μg/ml resveratrol can inhibit RPE migration. Both nicotinamide and resveratrol have no effect in cell adhesion platform. Further study showed that 1, 10, and100 μg/ml nicotinamide enhance the expression of integrin、cathepsin D、bFGF and CNTF.0.01and 0.1μg/ml of resveratrol enhance the expression of cathepsin D and HGF. These results indicate that nicotinamide and resveratrol may through enhance integrin 、 cathepsin D and bFGF expression and consequently phagocytosis. The protection effects of nicotinamide and resveratrol may increase cell viability through enhanced expression of CNTF、 HGF and bFGF.
In animal studies, we have set up ERG (Electroretinogram) platform and retinal degeneration models induced by Sodium iodate、N-methyl-N-nitrosourea or light that can cause retina partial functional damage for at least 7 days. We will evaluate the effects of nicotinamide by light damage model in mice in the future.
In our study, we find nicotinamide and resveratrol can promote RPE cell’s phagocytic activity, viability and dose not promote RPE cell’s proliferation and migration. We suggest that drugs may enhance RPE cell phagocytosis activity through stimulate integrin and cathepsin D expression, and also through the stimulated bFGF、CNTF,and HGF expression for the enhancement of RPE cell viability. It seems that nicotinamide and resveratrol could repair damaged retina by promoting RPE cell’s functions. Our data suggest that both compounds can be the potential drug candidatsfor the treatment of AMD.
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