Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2022, Vol. 36 ›› Issue (2): 72-77.doi: 10.6040/j.issn.1673-3770.0.2021.121

Previous Articles     Next Articles

Effect of intravitreal injection of HGF-MSCs on the expression of HGF in retina tissue of diabetic rats

WANG Hui1, WANG Jun2, SUN Yi1, YU Tengfei1, ZHU Yuguang2, ZHU Yan2   

  1. 1. College of Clinical Medicne, Weifang Medical University, Weifang 261053, Shandong, China;
    2. Ophthalmology Center, the Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong, China
  • Published:2022-04-15

PDF (PC)

163

Abstract: Objective To observe the effect of intravitreal injection of human umbilical cord mesenchymal stem cells(hUCMSCs)modified by the hepatocyte growth factor gene(HGF-MSCs)on the hepatocyte growth factor(HGF)expression in retina tissue of diabetic rats, and to explore the effect of HGF-MSCs on diabetic retinopathy in rats. Methods hUCMSCs were isolated, cultured, and identified. hUCMSCs were transfected with lentiviral vectors with a multiplicity of infection(MOI)of 50. Four-week-old Sprague-Dawley rats were randomly divided into the normal(15 rats)and diabetes(60 rats)groups. The diabetic rat models were established by intraperitoneal injection of streptozotocin(STZ). Three months after the diabetic rat models were confirmed successfully, the diabetes group was further divided into the diabetes control(no injection), PBS(intravitreal injection of PBS), MSCs(intravitreal injection of MSCs), and HGF-MSCs(intravitreal injection of HGF-MSCs)groups. After 2, 4, and 6 weeks of intravitreal injection, the HGF mRNA expression in rat retina was detected through real-time PCR. The expression of HGF in the rat retina was assessed through Western blot. Results The cultured hUCMSCs can be differentiated into osteoblasts and adipocytes. MOI 50 lentivirus successfully transfected hUCMSCs. Two weeks after intravitreal injection, quantitative real-time PCR and Western blot showed that, at the same time point, the expression of HGF and HGF mRNA in the normal group decreased compared to that of the other groups, and the difference was statistically significant(P<0.05). Compared with other groups at the same time point, the expression of HGF and HGF mRNA in HGF-MSCs group increased, and the difference was statistically significant(P<0.05). No significant difference in the expression of HGF and HGF mRNA was observed in the same group at different time points(P>0.05). Conclusion The HGF and HGF mRNA expression increased in diabetic rat retina. Intravitreal injection of hUCMSCs did not affect the HGF and HGF mRNA expression in diabetic rat retina. Intravitreal injection of hUCMSCs modified by HGF increased the HGF and HGF mRNA expression in diabetic rats. HGF-MSCs may interact with HGF to alleviate early diabetic retinopathy.

Key words: Diabetic retinopathy, Intravitreal injection, HGF, Transfection, hUCMSCs

CLC Number: 

  • R774.1
[1] 周玮琰, 王洪亚, 杜秀娟, 等. 甘糖酯对糖尿病大鼠视网膜病变中血管生成因子VEGF表达的影响[J]. 山东大学耳鼻喉眼学报, 2017, 31(2): 90-95. doi: 10.6040/j.issn.1673-3770.0.2016.146. ZHOU Weiyan, WANG Hongya, DU Xiujuan, et al. Effects of PGMS on the expression of vascular endothelial growth factor in the rat of diabetic retinopathy[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2017, 31(2): 90-95. doi: 10.6040/j.issn.1673-3770.0.2016.146.
[2] Sun JK, Jampol LM. The diabetic retinopathy clinical research network(DRCR.net)and its contributions to the treatment of diabetic retinopathy[J]. Ophthalmic Res, 2019, 62(4): 225-230.doi:10.1159/000502779.
[3] Tang PH, Hariprasad SM, Do DV. Rethinking management strategies for proliferative diabetic retinopathy[J]. Ophthalmic Surg Lasers Imaging Retina, 2018, 49(4): 224-227. doi:10.3928/23258160-20180329-01.
[4] Capitão M, Soares R. Angiogenesis and inflammation crosstalk in diabetic retinopathy[J]. J Cell Biochem, 2016, 117(11): 2443-2453. doi:10.1002/jcb.25575.
[5] Ezquer M, Urzua CA, Montecino S, et al. Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the Retina of diabetic mice[J]. Stem Cell Res Ther, 2016, 7: 42. doi:10.1186/s13287-016-0299-y.
[6] Wang LS, Wang H, Zhang QL, et al. Hepatocyte growth factor gene therapy for ischemic diseases[J]. Hum Gene Ther, 2018, 29(4): 413-423. doi:10.1089/hum.2017.217.
[7] Country MW. Retinal metabolism: a comparative look at energetics in the Retina[J]. Brain Res, 2017, 1672: 50-57. doi:10.1016/j.brainres.2017.07.025.
[8] 刘万智, 陈珺, 樊长春. 康柏西普治疗增生性糖尿病视网膜病变[J]. 山东大学耳鼻喉眼学报, 2018, 32(6): 88-91. doi: 10.6040/j.issn.1673-3770.0.2018.005. LIU Wanzhi, CHEN Jun, FAN Changchun. Clinical study of conbercept in the treatment of proliferative diabetic retinopathy[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(6): 88-91. doi: 10.6040/j.issn.1673-3770.0.2018.005.
[9] El Rami H, Barham R, Sun JK, et al. Evidence-based treatment of diabetic retinopathy[J]. Semin Ophthalmol, 2017, 32(1): 67-74. doi:10.1080/08820538.2016.1228397.
[10] Baker CW, Jiang Y, Stone T. Recent advancements in diabetic retinopathy treatment from the Diabetic Retinopathy Clinical Research Network[J]. Curr Opin Ophthalmol, 2016, 27(3): 210-216. doi:10.1097/icu.0000000000000262.
[11] Hammes HP, Lin J, Renner O, et al. Pericytes and the pathogenesis of diabetic retinopathy[J]. Diabetes, 2002, 51(10): 3107-3112. doi:10.2337/diabetes.51.10.3107.
[12] Yun JH, Park SW, Kim KJ, et al. Endothelial STAT3 activation increases vascular leakage through downregulating tight junction proteins: implications for diabetic retinopathy[J]. J Cell Physiol, 2017, 232(5): 1123-1134. doi:10.1002/jcp.25575.
[13] Yun JH, Koh YJ, Jeong HS, et al. Propranolol increases vascular permeability through pericyte apoptosis and exacerbates oxygen-induced retinopathy[J]. Biochem Biophys Res Commun, 2018, 503(4): 2792-2799. doi:10.1016/j.bbrc.2018.08.041.
[14] Yun JH. Hepatocyte growth factor prevents pericyte loss in diabetic retinopathy[J]. Microvasc Res, 2021, 133: 104103. doi:10.1016/j.mvr.2020.104103.
[15] Miyagi H, Thomasy SM, Russell P, et al. The role of hepatocyte growth factor in corneal wound healing[J]. Exp Eye Res, 2018, 166: 49-55. doi:10.1016/j.exer.2017.10.006.
[16] Cantón A, Burgos R, Hernández C, et al. Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy[J]. Br J Ophthalmol, 2000, 84(7): 732-735.doi:10.1136/bjo.84.7.732.
[17] Nowak M, Wielkoszyński T, Marek B, et al. A comparison of the levels of hepatocyte growth factor in serum in patients with type 1 diabetes mellitus with different stages of diabetic retinopathy[J].Endokrynologia Polska, 2008, 59(1): 2-5.
[18] Simó R, Vidal MT, García-Arumí J, et al. Intravitreous hepatocyte growth factor in patients with proliferative diabetic retinopathy: a case-control study[J]. Diabetes Res Clin Pract, 2006, 71(1): 36-44.doi:10.1016/j.diabres.2005.05.017.
[19] Yun JH. Hepatocyte growth factor prevents pericyte loss in diabetic retinopathy[J]. Microvasc Res, 2021, 133: 104103. doi:10.1016/j.mvr.2020.104103.
[20] Zakirova EY, Valeeva AN, Aimaletdinov AM, et al. Potential therapeutic application of mesenchymal stem cells in ophthalmology[J]. Exp Eye Res, 2019, 189: 107863. doi:10.1016/j.exer.2019.107863.
[21] Jin ZB, Gao ML, Deng WL, et al. Stemming retinal regeneration with pluripotent stem cells[J]. Prog Retin Eye Res, 2019, 69: 38-56. doi:10.1016/j.preteyeres.2018.11.003.
[22] Xu W, Wang XT, Xu GX, et al. Stromal cell-derived factor 1α-stimulated mesenchymal stem cells confer enhanced protection against light-induced retinal degeneration in rats[J]. Curr Eye Res, 2014, 39(1): 69-78. doi:10.3109/02713683.2013.824988.
[23] Deng W, Obrocka M, Fischer I, et al. In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP[J]. Biochem Biophys Res Commun, 2001, 282(1): 148-152. doi:10.1006/bbrc.2001.4570.
[24] Kim KS, Park JM, Kong T, et al. Retinal angiogenesis effects of TGF-β1 and paracrine factors secreted from human placental stem cells in response to a pathological environment[J]. Cell Transplant, 2016, 25(6): 1145-1157. doi:10.3727/096368915x688263.
[25] Mathot F, Shin AY, Van Wijnen AJ. Targeted stimulation of MSCs in peripheral nerve repair[J]. Gene, 2019, 710: 17-23. doi:10.1016/j.gene.2019.02.078.
[26] Hei WH, Almansoori AA, Sung MA, et al. Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor(BDNF)tohuman umbilical cord blood-derived mesenchymal stem cells(UCB-MSCs)promotescrush-injured rat sciatic nerve regeneration[J]. Neurosci Lett, 2017, 643: 111-120. doi:10.1016/j.neulet.2017.02.030.
[27] Fotia C, Massa A, Boriani F, et al. Prolonged exposure to hypoxic milieu improves the osteogenic potential of adipose derived stem cells[J]. J Cell Biochem, 2015, 116(7): 1442-1453.doi:10.1002/jcb.25106.
[28] El Barky AR, Ezz AAH, Alm-Eldeen AA, et al. Can stem cells ameliorate the pancreatic damage induced by streptozotocin in rats? [J]. Can J Diabetes, 2018, 42(1): 61-70. doi:10.1016/j.jcjd.2017.04.002.
[29] Choi KS, Shin JS, Lee JJ, et al. In vitro trans-differentiation of rat mesenchymal cells into insulin-producing cells by rat pancreatic extract[J]. Biochem Biophys Res Commun, 2005, 330(4): 1299-1305.doi:10.1016/j.bbrc.2005.03.111.
[1] WANG Jiaojiao, LI MiaoOverview,SONG ZongmingGuidance. Progress in diabetic retinopathy mechanisms and cellular models [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(5): 93-99.
[2] LIU Zhigao, WANG Shuya, HAN Xuguang, WANG Yu, LI Zhiwei, MA Aihua, ZHAO Bojun. Preoperative timing and the effect of intravitreal aflibercept injection for proliferative diabetic retinopathy patients [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(1): 99-103.
[3] LIU Jianbo, ZHANG Huan. Phacoemulsification combined with intravitreal ranibizumab or triamcinolone acetonide injection for the treatment of cataract accompanied by diabetic macular edema [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(2): 99-104.
[4] LI Baohua, LIU Ping, WANG Xin. Effect of beta elemene on the expression of IL-1 beta and ICAM-1 in the retina of diabetic rats [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(2): 111-114.
[5] WANG Xinjuan, SHA Shike, MA Lusheng. A case of transient monocular visual loss after vitrectomy for diabetic retinopathy [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(2): 171-172.
[6] LIU Wanzhi, CHEN Jun, FAN Changchun. Clinical study of conbercept in the treatment of proliferative diabetic retinopathy [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(6): 88-91.
[7] ZHOU Xueyi, LI Yiming, WANG Meiju, ZHANG Yuanyuan, ZHANG Lizhuo. The application of 25-gauge minimally invasive vitreoretinal surgery combined with intravitreal ranibizumab injections in the treatment of proliferative diabetic retinopathy. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2017, 31(4): 87-89.
[8] . Effects of PGMS on the expression of vascular endothelial growth factor in the rat of diabetic retinopathy. [J]. J Otolaryngol Ophthalmol Shandong Univ, 2017, 31(2): 90-95.
[9] YAN Xiaoteng, FENG Jun, KANG Xinle. Intravitreal injection of conbercept for macular edema secondary to retinal vein occlusion. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(4): 105-108.
[10] SHAO Na, ZHANG Han. Variation of visual acuity and fundus in type 2 diabetic patients after phacoemulsification surgery. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(1): 83-87.
[11] LI Junying. Effects of rosuvastatin combined with fenofibrate therapy on vascular endothelial function retinopathy diabetic retinopathy patients [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2015, 29(5): 72-75.
[12] CHAI Xuerong, ZHANG Shixi, TAO Yu, SHEN Jiaquan. Effect of intravitreal ranibizumab injection combined with trabelectomy and panretinal photocoagulation for neovascular glaucoma [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2015, 29(3): 72-75.
[13] LIU Zhi-gao, YAN Shi-long, HU Zun-xia, SUN Tong-xin, YANG Ming, WANG Yu. Prevalence investigation on rural cataract patients with diabetes and diabetes retinal fundus lesions in Jinan city of Shandong province [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2015, 29(1): 38-39.
[14] LIU Hai-yang, LI Su-yan, ZHANG Zheng-pei, FAN Wei. Comparison of improved membrane dissection and bimanual enbloc excision in 23G vitrectomy to treat proliferative diabetic retinopathy [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2015, 29(1): 52-55.
[15] MA Dong, GUO Cheng-wei. Collaterals therapy influences the expression of VCAM-1 in the retinal capillary wall of STZ-induced diabetic rats [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2015, 29(1): 64-68.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] MA Bao-feng,DANG Guang-fu .

Trans-scleral suture fixation in implantation of foldable intraocular lenses

[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(4): 376 -378 .
[2] FENG Xin-rong,ZHANG Hong-xia,XU Zhen-ji,QU Jun-jun, . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(3): 225 -226 .
[3] ZHANG Qiu-gui,HE Hai-yan . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(6): 520 -521 .
[4] LI Hai-yan,ZHAO Qiu-liang,HAN Xiao-pan,YU li . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(6): 527 -529 .
[5] SONG Xi-cheng,ZHANG hua,ZHANG Qing-quan . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(5): 385 -387 .
[6] ZHAN Shan-qiang,KONG Fan-li,CAO Wen-juan,TANG Jie . [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2006, 20(6): 559 -560 .
[7] ZHANG Hu,AI Qin . Re-operation for thyroid cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2007, 21(2): 166 -167 .
[8] HU Ming,LI Zhao-na,LI Yun-jie ,TAO Xiang-chen . Effect of rigid gas permeable contact lens on keratoconus[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2007, 21(2): 171 -173 .
[9] LOU Feng . Effect of bilateral superior laryngeal nerve block on preventing cardiovascular reaction[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2008, 22(2): 173 -175 .
[10] CHEN Wei-Xiong, WANG Yue-Jian, CENG Yong, HE Fa-Yao, ZHANG Jian-Li, ZHENG Li-Gang, TANG Su-Cheng. Clinical experience of no-insufflation endoscopic thyroidectomy by a small incision upon the sternum[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2009, 23(4): 24 -26 .
Website Copyright: Editorial Office of Journal of Otolaryngology and Ophthalmology of Shandong University
Address: No.27 Shanda South Road, Jinan, Shandong, China. Post code: 250100 Tel: +86-0531-88366912 Email: ebhxb@sdu.edu.cn Supported by Beijing Magtech Co.Ltd