Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China,
The Key Laboratory of Myopia, Ministry of Health, Shanghai, China,
Int J Nanomedicine. 2018 Dec 18;14:45-55. doi: 10.2147/IJN.S184574. eCollection 2019.
To pursuit effective sustained release systems for insulin to treat diabetic retinopathy (DR), a novel insulin delivering system was developed via loading onto chitosan nanoparticles/poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) hydrogel (ICNPH).
Examinations including electroretinography, HE staining, transmission electron microscopy, terminal deoxynucleotidyl transferased UTP nick-end labeling, immunofluorescence, Western blot, and real-time polymerase chain reaction were performed to evaluate the neuroprotective efficacy of ICNPH on DR by a single subconjunctival injection.
Compared with the insulin, blank, and sham treatment groups, subconjunctival injection of ICNPH significantly reduced the decrease of scotopic B-wave amplitude, alleviated retinal micro- and ultrastructural changes, and reduced retinal cell apoptosis caused in DR rats. Meanwhile, a significant reduction of vascular endothelial growth factor and glial fibrillary acidic protein expression as well as a remarkable increase in Occludin expression was also found in retinas in ICNPH group compared with the sham treatment group.
The results indicate that ICNPH has sufficient neuroprotective effect on retinas through subconjunctival injection in DR rats and facilitates controlled insulin delivery. It might be one of the therapeutic strategies for DR in the near future.
为了寻求有效的胰岛素持续释放系统来治疗糖尿病视网膜病变（DR），通过将胰岛素载入壳聚糖纳米粒子/聚（乳酸-共-乙醇酸）-聚（乙二醇）-聚（乳酸-共-乙醇酸）水凝胶（ICNPH）中，开发了一种新型的胰岛素递药系统。
通过单次结膜下注射，进行包括视网膜电图、HE 染色、透射电子显微镜、末端脱氧核苷酸转移酶 UTP 缺口末端标记、免疫荧光、Western blot 和实时聚合酶链反应在内的检查，以评估 ICNPH 对 DR 的神经保护作用。
与胰岛素、空白和假处理组相比，结膜下注射 ICNPH 可显著减少暗视野 B 波振幅的降低，缓解视网膜的微观和超微结构变化，并减少 DR 大鼠视网膜细胞凋亡。同时，与假处理组相比，ICNPH 组还发现血管内皮生长因子和胶质纤维酸性蛋白的表达显著减少，Occludin 的表达显著增加。
这些结果表明，通过结膜下注射 ICNPH 对 DR 大鼠的视网膜具有足够的神经保护作用，并促进了胰岛素的控释。它可能是未来治疗 DR 的一种治疗策略。
