Brain-derived neurotrophic factor and retinal ganglion cells in the retina of diabetic rat after intravitreal injection of human umbilical cord mesenchymal stem cells-induced neural stem cells_Chinese Journal of Ocular Fundus Diseases

Authors：

ZhangWei , WangYuexin ,  ChenSong , DuanHongtao , KongJiahui , DongMeng , BiXue , SongJian

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

Corresponding author：

ChenSong, Email: chensong20@hotmail.com

Keywords：

Diabetic retinopathy/therapy; Neural stem cells/transplantation; Brain-derived neurotrophic factor; Retinal ganglion cells; Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2016.06.009

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effect of intravitreal injection of neural stem cells (NSC) derived from human umbilical cord mesenchymal stem cells (hUCMSC) on the expression of brain-derived neurotrophic factor (BDNF) and the number of retinal ganglion cells (RGC). Methods Fifty-two adult male Sprague-Dawley rats were randomly divided into normal group (group A) and diabetes mellitus group which received intraperitoneal injection of streptozocin to make diabetic rat models. One month after the diabetic rat models were confirmed successfully, diabetic rats were randomly divided into diabetic group (group B), hUCMSC group (group C) and hUCMSC-induced NSC group (group D). And thirteen diabetic rats were included in each group. Immuno-cytochemistry was applied to observe BDNF and thymosin-1(Thy-1) staining in the retina. Then mean integrated absorbance of the staining region on the retina slices were analyzed by Image-Pro Plus 6.0. The number of Thy-1 labeled RGC was record. Results BDNF and Thy-1 were positive on the retina slices from group A. The staining intensity from group B became weak and the expression of BDNF and Thy-1 gradually decrease with time (P < 0.05), and those from group C and group D were positively (P < 0.05), especially in group D (P < 0.05). The BDNF expression and Thy-1 labeled RGC were the same between group B and C (P > 0.05) at 2 weeks after injection, but were significant different for other time points (P < 0.05).Significant positive correlation between the expression of BDNF and the number of RGC were found by the Pearson correlation analysis (r=0.964, P < 0.05). Conclusion Intravitreal injection of hUCMSC-derived NSC to diabetic rat may protect the retina by promoting the expression of BDNF and increasing the number of RGC.

Citation： ZhangWei, WangYuexin, ChenSong, DuanHongtao, KongJiahui, DongMeng, BiXue, SongJian. Brain-derived neurotrophic factor and retinal ganglion cells in the retina of diabetic rat after intravitreal injection of human umbilical cord mesenchymal stem cells-induced neural stem cells. Chinese Journal of Ocular Fundus Diseases, 2016, 32(6): 601-604. doi: 10.3760/cma.j.issn.1005-1015.2016.06.009 Copy

1.	Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy[J]. Diabetes Care, 2012, 35(3):556-564. DOI:10.2337/dc11-1909.
2.	Minguell JJ, Erices A, Conget P. Mesenchymal stem cells[J]. Exp Bio Med, 2001, 226(6):507-520.
3.	Si YL, Zhao YL, Hao HJ, et al. MSC:biological characteristics, clinical applications and their outstanding concerns[J]. Ageing Res Rev, 2011, 10(1):93-103. DOI:10.1016/j.arr.2010.08.005.
4.	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.
5.	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.
6.	Zhang W, Yan H. Simvastatin increases circulating endothelial progenitor cells and reduces the formation and progression of diabetic retinopathy in rats[J]. Exp Eye Res, 2012, 105:1-8. DOI:10.1016/j.exer.2012.09.014.
7.	Bocco BM, Werneck-de-Castro JP, Oliveira KC, et al. Type 2 deiodinase disruption in astrocytes results in anxiety-depressive-like behavior in male mice[J]. Endocrinology, 2016, 157(9):3682-3695. DOI:10.1210/en.2016-1272.
8.	Yang Z, Li K, Yan X, et al. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats[J]. Graefe's Arch Clin Exp Ophthalmol, 2010, 248(10):1415-1422. DOI:10.1007/s00417-010-1384-z.
9.	Koh SH, Kim KS, Choi MR, et al. Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats[J]. Brain Res, 2008, 1229:233-248. DOI:10.1016/j.brainres.2008.06.087.
10.	Cohen-Cory S, Escandon E, Fraser SE. The cellular patterns of BDNF and trkB expression suggest multiple roles for BDNF during xenopus visual system development[J]. Dev Biol, 1996, 179(1):102-115.
11.	Numakawa T, Suzuki S, Kumamaru E, et al. BDNF function and intracellular signaling in neurons[J]. Histol Histopathol, 2010, 25(2):237-258.
12.	Junyi L, Na L, Yan J. Mesenchymal stem cells secrete brain-derived neurotrophic factor and promote retinal ganglion cell survival after traumatic optic neuropathy[J]. J Craniofac Surg, 2015, 26(2):548-552. DOI:10.1097/SCS.0000000000001348.
13.	Feng L, Chen H, Yi J, et al. Long-term protection of retinal ganglion cells and visual function by brain-derived neurotrophic factor in mice with ocular hypertension[J]. Invest Ophthalmol Vis Sci, 2016, 57(8):3793-3802. DOI:10.1167/iovs.16-19825.

1. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy[J]. Diabetes Care, 2012, 35(3):556-564. DOI:10.2337/dc11-1909.
2. Minguell JJ, Erices A, Conget P. Mesenchymal stem cells[J]. Exp Bio Med, 2001, 226(6):507-520.
3. Si YL, Zhao YL, Hao HJ, et al. MSC:biological characteristics, clinical applications and their outstanding concerns[J]. Ageing Res Rev, 2011, 10(1):93-103. DOI:10.1016/j.arr.2010.08.005.
4. 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.
5. 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.
6. Zhang W, Yan H. Simvastatin increases circulating endothelial progenitor cells and reduces the formation and progression of diabetic retinopathy in rats[J]. Exp Eye Res, 2012, 105:1-8. DOI:10.1016/j.exer.2012.09.014.
7. Bocco BM, Werneck-de-Castro JP, Oliveira KC, et al. Type 2 deiodinase disruption in astrocytes results in anxiety-depressive-like behavior in male mice[J]. Endocrinology, 2016, 157(9):3682-3695. DOI:10.1210/en.2016-1272.
8. Yang Z, Li K, Yan X, et al. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats[J]. Graefe's Arch Clin Exp Ophthalmol, 2010, 248(10):1415-1422. DOI:10.1007/s00417-010-1384-z.
9. Koh SH, Kim KS, Choi MR, et al. Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats[J]. Brain Res, 2008, 1229:233-248. DOI:10.1016/j.brainres.2008.06.087.
10. Cohen-Cory S, Escandon E, Fraser SE. The cellular patterns of BDNF and trkB expression suggest multiple roles for BDNF during xenopus visual system development[J]. Dev Biol, 1996, 179(1):102-115.
11. Numakawa T, Suzuki S, Kumamaru E, et al. BDNF function and intracellular signaling in neurons[J]. Histol Histopathol, 2010, 25(2):237-258.
12. Junyi L, Na L, Yan J. Mesenchymal stem cells secrete brain-derived neurotrophic factor and promote retinal ganglion cell survival after traumatic optic neuropathy[J]. J Craniofac Surg, 2015, 26(2):548-552. DOI:10.1097/SCS.0000000000001348.
13. Feng L, Chen H, Yi J, et al. Long-term protection of retinal ganglion cells and visual function by brain-derived neurotrophic factor in mice with ocular hypertension[J]. Invest Ophthalmol Vis Sci, 2016, 57(8):3793-3802. DOI:10.1167/iovs.16-19825.

Chinese Journal of Ocular Fundus Diseases

Brain-derived neurotrophic factor and retinal ganglion cells in the retina of diabetic rat after intravitreal injection of human umbilical cord mesenchymal stem cells-induced neural stem cells

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