The effect of netrin-1 on activation of Müller cell in diabetes rats_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhou Xianhui ,  Meng Xuxia , Hu die

Department of Ophthalmology, The Affiliated of Qingdao University, Qingdao 266500, China (Zhou Xianhui, now working at the Department of Ophthalmology, Yantai YeDa Hospital; Hu Die, now working at the Qingdao Eye Hospital);

Corresponding author：

Meng Xuxia, Email: mengxuxia@163.com

Keywords：

Diabetic retinopathy/physiopathology; Microglia/physiology; Nerve growth factors; Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2017.05.020

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To observe the effect of netrin-1 on retinal Müller cells in diabetes mellitus (DM) rats. Methods Fifty Sprague-Dawley rats were randomly divided into the normal control group (group A), normal + balanced salt solution (BSS) group (group B), normal+netrin-1 group (group C), DM+BSS group (group D) and DM+netrin-1 group (group E), with 10 rats in each group. DM rats were induced by intraperitoneal injection of Streptozotocin (60 mg/kg). The expression level of glial fibrillary acidic protein (GFAP) on retinal Müller cells was determined by immunohistochemistry, the level of GFAP mRNA was analyzed by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Results Immunohistochemistry showed that GFAP was distributed in retinal ganglion cells and retinal nerve fiber layer in group A, B and C. Compared to group B, GFAP staining was brighter in the group D. There were significant differences in the expression of GFAP protein and mRNA among groups A-E (F=203.43, 72.91; P=0.00, 0.00), they were higher in group D than group A (t=−26.01, 22.26; P=0.00, 0.00), and group E (t=−10.78, 3.93; P=0.00, 0.00). They were higher in group E than group A (t=7.00, −9.82; P=0.00, 0.00). There were no significant differences in between group A and group C (t=−0.29, 0.50; P=0.77, 0.62). Conclusion The expression of GFAP in Müller cells of DM rats could be decreased by injecting netrin-1 into vitreous.

Citation： Zhou Xianhui, Meng Xuxia, Hu die. The effect of netrin-1 on activation of Müller cell in diabetes rats. Chinese Journal of Ocular Fundus Diseases, 2017, 33(5): 527-529. doi: 10.3760/cma.j.issn.1005-1015.2017.05.020 Copy

1.	Weerasekera LY, Balmer LA, Ram R, et al. Characterization of retinal vascular and neural damage in a novel model of diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2015, 56(6): 3721-3730. DOI: 10.1167/iovs.14-16289.
2.	Rodrigues M, Xin X, Jee K, et al. VEGF secreted by hypoxic Müller cells induces MMP-2 expression and activity in endothelial cells to promote retinal neovascularization in proliferative diabetic retinopathy[J]. Diabetes, 2013, 62 (11): 3863-3873. DOI: 10.2337/db13-0014.
3.	Roy S, Amin S, Roy S. Retinal fibrosis in diabetic retinopathy[J]. Exp Eye Res, 2016, 142: 71-75. DOI: 10.1016/j.exer.2015.04.004.
4.	Lv J, Sun X, Ma J, et al. Netrin-1 induces the migration of Schwann cells via p38 MAPK and PI3K-Akt signaling pathway mediated by the UNC5B receptor[J]. Biochem Biophys Res Commun, 2015, 464(1): 263-268. DOI: 10.1016/j.bbrc.2015.06.140.
5.	Ke X, Liu C, Wang Y, et al. Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia[J]. Diab Vasc Dis Res, 2016, 13(2): 145-156. DOI: 10.1177/1479164115611594.
6.	Algandaby MM, Alghamdi HA, Ashour OM, et al. Mechanisms of the antihyperglycemic activity of Retama raetam in streptozotocin induced diabetic rats[J]. Food Chem Toxicol, 2010, 48(8-9): 2448-2453. Doi: 10.1016/j.fct.2010.06.010.
7.	Chang ML, Wu CH, Jiang-Shieh YF, et al. Reactive changes of retinal astrocytes and Müller glial cells in kainate-induced neuroexcitotoxicity[J]. J Anat, 2007, 210 (1): 54-65.
8.	Zhong Y, Li J, Chen Y, et al. Activation of endoplasmic reticulum stress by hyperglycemia is essential for Müller cell-derived inflammatory cytokine production in diabetes[J]. Diabetes, 2012, 61(2): 492-504. DOI: 10.2337/db11-0315.
9.	Zhou KK, Benyajati S, Le Y, et al. Interruption of Wnt signaling in Müller cells ameliorates ischemia-induced retinal neovascularization[J/OL]. PLoS One, 2014, 9(10): 108454[2014-10-01]. http://dx.plos.org/10.1371/journal.pone.0108454. DOI: 10.1371/journal.pone.0108454.
10.	Fu S, Dong S, Zhu M, et al. Müller glia are a major cellular source of survival signals for retinal neurons in diabetes[J]. Diabetes, 2015, 64 (10): 3554-3563. DOI: 10.2337/db15-0180.
11.	Midena E, Pilotto E.Emerging insights into pathogenesis[J]. Dev Ophthalmol, 2017, 60: 16-27. DOI: 10.1159/000459687.
12.	周贤慧, 孟旭霞, 孙运波, 等. 轴突导向因子 netrin-1 对早期糖尿病大鼠血视网膜屏障的影响[J]. 中华眼底病杂志, 2015, 31(5): 472-476. DOI: 10.3760/cma.j.issn.1005-1015.2015.05.015.Zhou XH, Meng XX, Sun YB, et al. The effect of netrin-1 on the retinal vascular permeability in early diabetic retinopathy rats[J]. Chin J Ocul Fundus Dis, 2015, 31(5): 472-476. DOI: 10.3760/cma.j.issn.1005-1015.2015.05.015.

1. Weerasekera LY, Balmer LA, Ram R, et al. Characterization of retinal vascular and neural damage in a novel model of diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2015, 56(6): 3721-3730. DOI: 10.1167/iovs.14-16289.
2. Rodrigues M, Xin X, Jee K, et al. VEGF secreted by hypoxic Müller cells induces MMP-2 expression and activity in endothelial cells to promote retinal neovascularization in proliferative diabetic retinopathy[J]. Diabetes, 2013, 62 (11): 3863-3873. DOI: 10.2337/db13-0014.
3. Roy S, Amin S, Roy S. Retinal fibrosis in diabetic retinopathy[J]. Exp Eye Res, 2016, 142: 71-75. DOI: 10.1016/j.exer.2015.04.004.
4. Lv J, Sun X, Ma J, et al. Netrin-1 induces the migration of Schwann cells via p38 MAPK and PI3K-Akt signaling pathway mediated by the UNC5B receptor[J]. Biochem Biophys Res Commun, 2015, 464(1): 263-268. DOI: 10.1016/j.bbrc.2015.06.140.
5. Ke X, Liu C, Wang Y, et al. Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia[J]. Diab Vasc Dis Res, 2016, 13(2): 145-156. DOI: 10.1177/1479164115611594.
6. Algandaby MM, Alghamdi HA, Ashour OM, et al. Mechanisms of the antihyperglycemic activity of Retama raetam in streptozotocin induced diabetic rats[J]. Food Chem Toxicol, 2010, 48(8-9): 2448-2453. Doi: 10.1016/j.fct.2010.06.010.
7. Chang ML, Wu CH, Jiang-Shieh YF, et al. Reactive changes of retinal astrocytes and Müller glial cells in kainate-induced neuroexcitotoxicity[J]. J Anat, 2007, 210 (1): 54-65.
8. Zhong Y, Li J, Chen Y, et al. Activation of endoplasmic reticulum stress by hyperglycemia is essential for Müller cell-derived inflammatory cytokine production in diabetes[J]. Diabetes, 2012, 61(2): 492-504. DOI: 10.2337/db11-0315.
9. Zhou KK, Benyajati S, Le Y, et al. Interruption of Wnt signaling in Müller cells ameliorates ischemia-induced retinal neovascularization[J/OL]. PLoS One, 2014, 9(10): 108454[2014-10-01]. http://dx.plos.org/10.1371/journal.pone.0108454. DOI: 10.1371/journal.pone.0108454.
10. Fu S, Dong S, Zhu M, et al. Müller glia are a major cellular source of survival signals for retinal neurons in diabetes[J]. Diabetes, 2015, 64 (10): 3554-3563. DOI: 10.2337/db15-0180.
11. Midena E, Pilotto E.Emerging insights into pathogenesis[J]. Dev Ophthalmol, 2017, 60: 16-27. DOI: 10.1159/000459687.
12. 周贤慧, 孟旭霞, 孙运波, 等. 轴突导向因子 netrin-1 对早期糖尿病大鼠血视网膜屏障的影响[J]. 中华眼底病杂志, 2015, 31(5): 472-476. DOI: 10.3760/cma.j.issn.1005-1015.2015.05.015.Zhou XH, Meng XX, Sun YB, et al. The effect of netrin-1 on the retinal vascular permeability in early diabetic retinopathy rats[J]. Chin J Ocul Fundus Dis, 2015, 31(5): 472-476. DOI: 10.3760/cma.j.issn.1005-1015.2015.05.015.

Chinese Journal of Ocular Fundus Diseases

The effect of netrin-1 on activation of Müller cell in diabetes rats

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