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Shifts in renin–angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice

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Abstract

Purpose

This study aimed to analyse shifts in renin–angiotensin system (RAS) components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa (LC) region in streptozotocin (STZ)-induced diabetic mice.

Methods

Six months after diabetes induction, the retinal vessels of male C57BL/6 J mice were observed by colour photography, fundus fluorescein angiography (FFA), and immunofluorescent staining following incubation with CD31. Immunofluorescence for glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA),and NG2 was also performed. Angiotensin-converting enzyme 1 (ACE1), angiotensin II type I receptor (AT1R), renin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and haeme oxygenase 1 (HO-1) expression levels were confirmed by immunohistochemical and western blotting analyses.

Results

Compared with control mice, diabetic mice had significantly higher blood glucose concentrations (p < 0.001) and significantly lower body weights (p < 0.001). Colour photography and FFA did not reveal any vessel abnormalities in the diabetic mice; however, immunostaining of whole-mount retinas revealed an increased number of retinal vessels. Furthermore, histopathological staining showed significant reduction in the whole retinal thickness. GFAP expression was slightly higher, whereas fewer NG2+ pericytes were observed in diabetic mice than in control mice. ACE1, AT1R, renin, HIF-1α, VEGF, VEGFR2, and HO-1 expression were up-regulated in the LC of the STZ-induced diabetic mice.

Conclusions

Collectively, ACE 1, AT1R, HIF-1α, VEGF, VEGFR2, and HO-1 activation in the LC region in diabetic mice may be involved in diabetes via the RAS and induction of angiogenesis and oxidative stress.

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Acknowledgements

We thank Zhiquan Li taking care of mice, Xiaoxiao Feng and Cheng Li, for developmental review of the manuscript.

Funding

This study was funded by the National Science & Technology Pillar Program of the Twelfth Five-year Plan (2012BAI08B00), the Science and Technology Planning Project of Guangdong Province, China (2015B020211004).

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Authors and Affiliations

  1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China

    Xiaobing Qian, Leilei Lin, Yao Zong, Yongguang Yuan, Yanmin Dong, Yue Fu, Wanwen Shao, Yujie Li & Qianying Gao

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  1. Xiaobing Qian
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Correspondence to Qianying Gao.

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Qian, X., Lin, L., Zong, Y. et al. Shifts in renin–angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice. Graefes Arch Clin Exp Ophthalmol 256, 525–534 (2018). https://doi.org/10.1007/s00417-017-3866-8

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