The effects on the function and structure of retina in diabetic rats by intravitreal transplantation of human umbilical cord cells-induced neuronal stem cells_Chinese Journal of Ocular Fundus Diseases

Authors：

JiangJianhong , KongJiahui ,  ChenSong , DuanHongtao , WangYuexin , DongMeng , ZhangWei , WangYun , LinJinyong

Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, The Ophthalmic College of Tianjin Medical University, Tianjin 300020, China;

Corresponding author：

ChenSong, Email: chensong20@hotmail.com

Keywords：

Neural stem cells/transplantation; Diabetic retinopathy/therapy; Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2016.04.017

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Objective To observe the effects on the function and structure of retina in diabetic rats by intravitreal transplantation of retinal nerve stem cells (NSC) differentiated from human umbilical cord mesenchymal stem cells (hUCMSCs). Methods Fifty clean male Sprague-Dawley rats were randomly divided into normal control with 9 rats (group A) and diabetes mellitus (DM) group with 31 rats. The DM models were induced by intraperitoneal injection of streptozocin. The rats of DM group were randomly divided into four groups after 10 weeks: rats with DM only (group B), diabetic rats with saline intravitreal injection (group C), diabetic rats with NSC intravitreal injection (group D), and 9 rats for each. The rats in the group A and B received no treatment. The retinal function was examined by the flash-electroretinogram on 2, 4, 6 weeks after intervention, the latency and amplitude of a-wave, b-wave of Rod, a-wave, b-wave of Max reactions (Max-R) and the total amplitudes of OPs were recorded. The morphological changes of retina were observed by hematoxylin-eosin staining. Results On 2 and 4 weeks after the intervention, the differences of latency and amplitude of b-wave of Rod, a-wave, b-wave of Max-R and the total amplitudes of OPs among group A-D were significant (P<0.05). Compared group D with group B, C, the amplitude of b-wave of Rod, Max-R and the total amplitudes of OPs were increased (P<0.05); latency of b-wave of Max-R was decreased (P<0.05). On 6 weeks after the intervention, the amplitude of b-wave of Rod and the amplitude of a-wave, b-wave of Max-R and the total amplitudes of OPs in group D were increased compared with group B and C (P<0.05), the latency of b-wave of Rod and Max-R in group D were decreased compared with group C (P<0.05). On 10 weeks after molding, each retinal layers were disordered in diabetes mellitus group. On 2 weeks after the intervention, the number of cells in the retinal layers in group B and C were reduced compared with group A, and the structure was more disorder. On 4 weeks after the intervention, the structure of each retina layer in group D arranged less disordered, and the number of retinal ganglion cells was more than group B and C. It was also found that the retinal vascular endothelial expanded and retinal blood vessels cells proliferated. Conclusion The function of retina in diabetes mellitus rats is improved by intravitreal injection of retinal NSCs differentiated from hUCMSCs.

Citation： JiangJianhong, KongJiahui, ChenSong, DuanHongtao, WangYuexin, DongMeng, ZhangWei, WangYun, LinJinyong. The effects on the function and structure of retina in diabetic rats by intravitreal transplantation of human umbilical cord cells-induced neuronal stem cells. Chinese Journal of Ocular Fundus Diseases, 2016, 32(4): 418-422. doi: 10.3760/cma.j.issn.1005-1015.2016.04.017 Copy

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1. Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy[J]. N Engl J Med, 2012, 366(13):1227-1239. DOI:10.1056/NEJMra1005073.
2. Peng J, Wang Y, Zhang L, et al. Human umbilical cord Wharton's jelly-derived mesenchymal stem cells differentiate into a Schwann-cell phenotype and promote neurite outgrowth in vitro[J]. Brain Res Bull, 2011, 84(3):235-243.DOI:10.1016/j.brainresbull.2010.12.013.
3. Wang S, Lu B, Girman S, et al. Non invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology[J/OL]. PLoS One, 2010, 5(2):9200[2010-02-15].http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821411/.DOI:10.1371/journal.pone.0009200.
4. Arnhold S, Absenger Y, Klein H, et al. Transplantation of bone marrow derived mesenchymal stem cells rescue photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse[J]. Graefe's Arch Clin Exp Ophthalmol, 2007, 245(3):414-442.
5. Tolar J, Nauta AJ, Osborn MJ,et al. Sarcoma derived from cultured mesenchymal stem cells[J].Stem Cells, 2007, 25(2):371-379.
6. Chen S, Zhang W, Wang JM, et al. Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells[J]. Int J Ophthalmol, 2016, 9(1):41-47.DOI:10.18240/ijo.2016.01.07.
7. Serrarbassa PD, Dias AF, Vieira MF. New concepts on diabetic retinopathy:neural versus vascular damage[J]. Arq Bras Oftalmol, 2008, 71(3):459-463.
8. Fletcher EL, Phipps JA, Ward MM, et al. Neuronal and glial cell abnormality as predictors of progression of diabetic retinopathy[J]. Curr Pharm Des, 2007, 13(26):2699-2712.
9. Li Q, Zemel E, Miller B, et al. Early retinal damage in experimental diabetes:electroretinographical and morphological observations[J]. Exp Eye Res, 2002, 74(5):615-625.
10. 徐星慧, 张武峰.亚临床期糖尿病视网膜病变的早期诊断[J].国际眼科杂志,2014, 14(12):2214-2216. Xu XH, Zhang WF. Early diagnosis of sub-clinical stage of diabetic retinopathy[J]. Int Eye Sci, 2014, 14(12):2214-2216.
11. Lee CA, Li G, Patel MD, et al. Diabetes-induced impairment in visual function in mice:contributions of p38 MAPK, RAGE, leukocytes, and aldose reductase[J]. Invest Ophthalmol Vis Sci, 2014, 55(5):2904-2910. DOI:10.1167/iovs.13-11659.
12. Dobson R,Lawden M.Melanoma associated retinopathy and how to understand the electroretinogram[J].Pract Neurol, 2011,11(4):234-239. DOI:10.1136/practneurol-2011-000061.
13. Kowluru RA, Zhong Q, Santos JM, et al. Beneficial effects of the nutritional supplements on the development of diabetic retinopathy[J].Nutr Metab (Lond), 2014, 11(1):8. DOI:10.1186/1743-7075-11-8.

Chinese Journal of Ocular Fundus Diseases

The effects on the function and structure of retina in diabetic rats by intravitreal transplantation of human umbilical cord cells-induced neuronal stem cells

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