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酶诱导的玻璃体溶解可以通过 HIF-1α 通路缓解糖尿病视网膜病变的进展。

Enzyme-induced vitreolysis can alleviate the progression of diabetic retinopathy through the HIF-1α pathway.

机构信息

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Invest Ophthalmol Vis Sci. 2013 Jul 26;54(7):4964-70. doi: 10.1167/iovs.12-11443.

DOI:10.1167/iovs.12-11443
PMID:23847321
Abstract

PURPOSE

We studied the mechanism by which complete posterior vitreous detachment by enzyme-induced vitreolysis alleviates the progression of diabetic retinopathy.

METHODS

We enrolled 50 diabetic rats and 20 normal control rats in this study. The right eyes of these diabetic rats were treated with a hyaluronidase (5 U) plus plasmin (0.25 U) by intravitreous injection (ET group), while the left eyes of diabetic rats (DR group) and eyes of the normal rats (NC group) were injected with balanced saline. Eight months after intravitreous injection, the oxygen concentration in the vitreous was measured, and the expression levels of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), and basic fibroblast growth factor (bFGF) in retinas were determined by real-time PCR and Western blot. Clinical observation, visual electrophysiology tests, and scanning electron microscopy (SEM) also were performed on the rats.

RESULTS

SEM results showed that the surface of retinas in the ET group had little vitreous cortex and the inner limiting membrane could be observed. The oxygen concentration of the midvitreous was higher in the ET group than other groups. A significantly high expression of HIF-1α, VEGF, and bFGF was detected in the retinas of the DR group compared to the ET and NC groups. In visual electrophysiology tests, amplitude decline and peak time latency were found in diabetic rats, and changes in the DR group were more obvious than in the ET group.

CONCLUSIONS

Enzyme-induced vitreolysis can increase oxygen concentration in the vitreous, with reduced expression of HIF-1α, VEGF, and bFGF, and increased expression of PEDF in the retinas, thus alleviating the progression of diabetic retinopathy.

摘要

目的

我们研究了酶诱导玻璃体裂解引起的完全玻璃体后脱离缓解糖尿病视网膜病变进展的机制。

方法

本研究纳入 50 只糖尿病大鼠和 20 只正常对照大鼠。将透明质酸酶(5 U)加纤溶酶(0.25 U)通过玻璃体腔内注射入这些糖尿病大鼠的右眼(ET 组),而糖尿病大鼠的左眼(DR 组)和正常大鼠的眼睛(NC 组)则注射平衡盐溶液。玻璃体腔内注射 8 个月后,测量玻璃体中的氧浓度,并通过实时 PCR 和 Western blot 测定视网膜中缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)、色素上皮衍生因子(PEDF)和碱性成纤维细胞生长因子(bFGF)的表达水平。还对大鼠进行临床观察、视觉电生理学测试和扫描电子显微镜(SEM)检查。

结果

SEM 结果显示,ET 组视网膜表面玻璃体皮质较少,内界膜可见。ET 组玻璃体中部的氧浓度高于其他组。与 ET 和 NC 组相比,DR 组视网膜中 HIF-1α、VEGF 和 bFGF 的表达明显升高。在视觉电生理学测试中,糖尿病大鼠的振幅下降和峰值时间潜伏期发现,DR 组的变化比 ET 组更明显。

结论

酶诱导玻璃体裂解可增加玻璃体中的氧浓度,降低 HIF-1α、VEGF 和 bFGF 的表达,增加视网膜中 PEDF 的表达,从而缓解糖尿病视网膜病变的进展。

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