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Original Research

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

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Pages 45-55 | Published online: 18 Dec 2018
 

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.