視網(wǎng)膜鐵代謝與年齡相關(guān)性黃斑變性實(shí)驗(yàn)研究
[Abstract]:Age-related macular degeneration (age related macular degeneration, AMD) is one of the main diseases affecting the visual function of the elderly. Oxidative stress is an important pathogenesis of age-related macular degeneration. Reactive oxygen species cluster can promote the pathological changes of retinal degeneration. Iron can produce reactive oxygen species by Fenton reaction, and excessive iron can induce oxidative stress damage. Abnormal iron metabolism may be involved in the occurrence and development of age-related macular degeneration by inducing oxidative stress damage. Iron regulatory protein (hepcidin Hepc) is an important factor in the regulation of iron metabolism. It can be combined with membrane iron transporter 1 (FPN) and degrade the latter. Because Fpn is the only known pathway of iron excretion, so, The fine regulation of iron regulatory proteins plays an important role in maintaining the homeostasis of iron in cells. The aim of this study was to investigate the regulatory mechanism of iron regulatory proteins in the retina and the protective effect of iron chelating agents on iron overload retina. In order to investigate the regulatory mechanism of iron regulatory protein, the bonemorphogenetic protein 6 (bonemorphogenetic protein 6 Bmp6) gene knockout mice were used in this study. The liver specific knockout mice of Hepc gene were injected with iron sucrose injection (iron sucrose injection Venofer. Morphological and biochemical indexes were detected by real-time PCR, so as to explore the regulatory mechanism of iron regulatory proteins in the retina. The results showed that the retinal iron level of Bmp6 knockout mice gradually accumulated with age, and the expression of HEC was not affected by Bmp6 knockout, and increased with the increase of retinal iron level. The iron level of the retina of the Hepc liver-specific knockout mice increased with age and was significantly higher than that of the control group. Iron overload occurred in the retinal pigment epithelium (retinal pigment epithelium of the C57BL/6J mice treated with iron. Although the expression of local iron regulatory protein changed, it could not resist the change of iron level and decrease the absorption of iron in retina. In conclusion, iron regulatory proteins play a role in the local retina, and their regulation is not affected by the Bmp6 pathway. The iron level in the circulation is an important factor of iron regulatory proteins. In order to investigate the protective effect of deferriferone on the retina, the Hepc gene knockout mice model was used in this study. After 12 months of DFP intervention, the mice were killed, and (ERG), fundus photography was performed by electroretinography. Retinal function, morphology and molecular biological indexes were detected by real-time PCR. The results showed that not only the function of the retina was less damaged than that of the control group, but also the number and degree of autofluorescence and mast cells in the photoreceptor cells were less than those in the control group. The results of molecular biology showed that the expression levels of rhodopsin Rho and RPE65 were significantly higher than those of the control group. The results suggest that DFP can significantly reduce the level of iron in the retina, reduce the level of oxidative stress and protect the retinal function.
【學(xué)位授予單位】:吉林大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2015
【分類號】:R774.1
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