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Retrobulbarly injecting nerve growth factor attenuates visual impairment in streptozotocin-induced diabetes rats

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Abstract

Purpose

To explore whether retrobulbar administration of nerve growth factor (NGF) can restore visual function of streptozotocin-induced diabetes rats.

Methods

A high-sucrose/high-fat diet and single injection of streptozotocin (STZ) were used in modeling diabetes. During week 13–15 after STZ injection, diabetic rats were received retrobulbar βNGF injection. On week 17 after STZ injection, the rats were tested with flash visual evoked potential (FVEP) to reflect visual function and with both optical coherence tomography (OCT) and hematoxylin and eosin (H&E) staining to show retinal morphological changes. Furthermore, periodic acid-Schiff (PAS) staining for retinal vascular digest preparations was performed to investigate retinal microvascular alterations, and immunofluorescences for slides of the optic nerve or retina were checked to assess astrocyte activation, autophagy level, and the unfolded protein response (UPR).

Results

Retrobulbar βNGF injection significantly improved FVEP of diabetic rats. It also significantly alleviated retinal ganglion cell (RGC) loss and scarcely elicited other retinal/microvascular morphological changes, in OCT, H&E staining, and microvascular preparation. Moreover when diabetes rats treated with NGF, immunostaining of the optic nerve showed downregulation of complement 3d (C3d) and upregulations of glial fibrillary acidic protein (GFAP), S100-A10, microtubule-associated proteins 1A/1B light chain 3b (LC3b), and activating transcription factor 4 (ATF-4), while immunostaining of the retina showed upregulation of LC3b and no expression of ATF-4.

Conclusion

Our findings demonstrate that retrobulbar administration of βNGF reduces visual impairment with RGC-loss attenuation and without retinal-microvascular morphological alteration in diabetic rats. Furthermore, enhancements of A2 astrocyte activation, autophagy-protein expression, and ATF-4-mediated UPR may play crucial roles in the protective mechanism of NGF in diabetic visual-pathway neurodegeneration.

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Acknowledgements

We thank Pro. Jian-Su Chen for her expert assistance.

Funding

Supported by the Fundamental Research Funds for the Central Universities of Central South University (No. 2019zzts368), and by Project of Changsha Science and Technology Bureau (No. KH180123).

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Authors and Affiliations

  1. Aier School of Ophthalmology, Central South University, Changsha, Hunan Province, 410015, China

    Qi-Chang Wang, Wang Sheng, Cai-Jiao Yi, Han Lv & Bei Cheng

  2. Changsha Xiangjiang, Aier Eye Hospital, Changsha, Hunan Province, 410015, China

    Qi-Chang Wang

  3. Aier Eye Institute, Changsha, Hunan Province, 410015, China

    Wang Sheng, Cai-Jiao Yi, Han Lv & Bei Cheng

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  1. Qi-Chang Wang
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Correspondence to Qi-Chang Wang.

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The animal research was approved by the Animal Welfare and Ethics Committee of Central South University and was conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Wang, QC., Sheng, W., Yi, CJ. et al. Retrobulbarly injecting nerve growth factor attenuates visual impairment in streptozotocin-induced diabetes rats. Int Ophthalmol 40, 3501–3511 (2020). https://doi.org/10.1007/s10792-020-01537-8

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  • DOI: https://doi.org/10.1007/s10792-020-01537-8

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