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International Journal of Nanomedicine Volume 14, 2019 - Issue
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Original Research

Neuroprotective effect of insulin-loaded chitosan nanoparticles/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats

Xianfang Rong1 Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China, [email protected]; [email protected];2 The Key Laboratory of Myopia, Ministry of Health, Shanghai, China, [email protected]; [email protected];3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China, [email protected]; [email protected];4 Key National Health Committee Key Laboratory of Myopia, Fudan University, Shanghai, China, [email protected]; [email protected];5 Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China, [email protected]; [email protected]
,
Yinghong Ji1 Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China, [email protected]; [email protected];2 The Key Laboratory of Myopia, Ministry of Health, Shanghai, China, [email protected]; [email protected];3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China, [email protected]; [email protected];4 Key National Health Committee Key Laboratory of Myopia, Fudan University, Shanghai, China, [email protected]; [email protected];5 Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China, [email protected]; [email protected]
,
Xiangjia Zhu1 Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China, [email protected]; [email protected];2 The Key Laboratory of Myopia, Ministry of Health, Shanghai, China, [email protected]; [email protected];3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China, [email protected]; [email protected];4 Key National Health Committee Key Laboratory of Myopia, Fudan University, Shanghai, China, [email protected]; [email protected];5 Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China, [email protected]; [email protected]
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Jin Yang1 Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China, [email protected]; [email protected];2 The Key Laboratory of Myopia, Ministry of Health, Shanghai, China, [email protected]; [email protected];3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China, [email protected]; [email protected];4 Key National Health Committee Key Laboratory of Myopia, Fudan University, Shanghai, China, [email protected]; [email protected];5 Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China, [email protected]; [email protected]
,
Dongjin Qian1 Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China, [email protected]; [email protected];2 The Key Laboratory of Myopia, Ministry of Health, Shanghai, China, [email protected]; [email protected];3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China, [email protected]; [email protected];4 Key National Health Committee Key Laboratory of Myopia, Fudan University, Shanghai, China, [email protected]; [email protected];5 Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China, [email protected]; [email protected]
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Xiaofen Mo1 Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China, [email protected]; [email protected];2 The Key Laboratory of Myopia, Ministry of Health, Shanghai, China, [email protected]; [email protected];3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China, [email protected]; [email protected];4 Key National Health Committee Key Laboratory of Myopia, Fudan University, Shanghai, China, [email protected]; [email protected];5 Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China, [email protected]; [email protected]Correspondence[email protected] [email protected]
&
Yi Lu1 Department of Ophthalmology and The Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China, [email protected]; [email protected];2 The Key Laboratory of Myopia, Ministry of Health, Shanghai, China, [email protected]; [email protected];3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China, [email protected]; [email protected];4 Key National Health Committee Key Laboratory of Myopia, Fudan University, Shanghai, China, [email protected]; [email protected];5 Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China, [email protected]; [email protected]Correspondence[email protected] [email protected]
 show all
Pages 45-55 | Published online: 18 Dec 2018
 
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Abstract

Background

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).

Methods and materials

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.

Results

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.

Conclusion

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.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant nos. 813008068, 81570842, 81770907, 81470613, 81100653, 81670835, and 81270989), Shanghai High Myopia Study Group, International Science and Technology Cooperation Foundation of Shanghai (grant no. 14430721100), Shanghai Talent Development Fund (grant no. 201604), Shanghai Youth Doctor Support Program (grant no. 2014118), and Outstanding Youth Medical Talents Program of Shanghai Health and Family Planning Commission (2017YQ011). The fund providers played no part in study design, data collection, analysis, decision to publish, or manuscript preparation.

Disclosure

The authors report no conflicts of interest in this work.

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