PMID- 29505314 OWN - NLM STAT- MEDLINE DCOM- 20190516 LR - 20190516 IS - 1460-2202 (Electronic) IS - 0271-3683 (Linking) VI - 43 IP - 6 DP - 2018 Jun TI - Neuroprotection of Transplanting Human Umbilical Cord Mesenchymal Stem Cells in a Microbead Induced Ocular Hypertension Rat Model. PG - 810-820 LID - 10.1080/02713683.2018.1440604 [doi] AB - PURPOSE: The purpose of this study is to investigate the potential therapeutic benefits of intravitreally transplanted human umbilical cord mesenchymal stem cells (UC-MSCs) in an animal model of microbead-injection-induced ocular hypertension (OHT). METHODS: UC-MSCs were isolated from human umbilical cords and then cultured. The OHT model was induced via intracameral injection of polystyrene microbeads in Sprague-Dawley adult rat eyes. Fifty-four healthy adult rats were randomly divided into three groups: normal control, OHT model treated with intravitreal transplantation of UC-MSCs, or phosphate-buffered saline (PBS). Two days after OHT was induced, either 5 microl 10(5) UC-MSCs suspension or PBS was injected into the vitreous cavity of rats. UC-MSCs localization and integration were examined via immunohistochemistry. Neuroprotection was quantified by counting retinal ganglion cells (RGCs) and axons 2 weeks following transplantation. The expression levels of glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) were assessed via immunohistochemistry and Western blot. Functional recovery was assessed 2 weeks after transplantation via scotopic threshold response (STR) electroretinography. RESULTS: Elevated IOP levels were sustained at least 3 weeks after intracameral microbead injection and the number of beta-III-tubulin(+) RGCs significantly declined compared to PBS-injected eyes. UC-MSCs survived for at least 2 weeks after intravitreal transplantation and predominantly located in the vitreous cavity. A fraction of cells migrated into the ganglion cell layer of host retina, but without differentiation. Intravitreal UC-MSC transplantation resulted in increased number of RGCs, axons, and increased expression of GDNF and BDNF but decreased expression of GFAP. Intravitreal delivery of UC-MSCs significantly improved the recovery of the positive STR. CONCLUSIONS: Intravitreal transplantation of UC-MSCs revealed the neuroprotection in the microbead-injection induced OHT. The effects could be related to the secretion of tropic factors (BDNF and GDNF) and the modulation of glial cell activation. FAU - Ji, Shangli AU - Ji S AD - a Aier School of Ophthalmology , Central South University , Changsha , Hunan , China. FAU - Lin, Saiyue AU - Lin S AD - b Department of Anatomy and Neurobiology, Xiangya School of Medicine , Central South University , Changsha , Hunan , China. FAU - Chen, Jiansu AU - Chen J AD - a Aier School of Ophthalmology , Central South University , Changsha , Hunan , China. FAU - Huang, Xinping AU - Huang X AD - c Department of Biology , ShenzhenHornetcorn Biotechnology Co., Ltd , Shenzhen , Guangdong , China. FAU - Wei, Chih-Chang AU - Wei CC AD - c Department of Biology , ShenzhenHornetcorn Biotechnology Co., Ltd , Shenzhen , Guangdong , China. FAU - Li, Zhiyuan AU - Li Z AD - b Department of Anatomy and Neurobiology, Xiangya School of Medicine , Central South University , Changsha , Hunan , China. FAU - Tang, Shibo AU - Tang S AD - a Aier School of Ophthalmology , Central South University , Changsha , Hunan , China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180305 PL - England TA - Curr Eye Res JT - Current eye research JID - 8104312 SB - IM MH - Animals MH - Cell Count MH - Cell Differentiation MH - Disease Models, Animal MH - Intraocular Pressure/*physiology MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*cytology MH - Microspheres MH - *Neuroprotection MH - Ocular Hypertension/diagnosis/physiopathology/*therapy MH - Rats MH - Rats, Sprague-Dawley MH - Retinal Ganglion Cells/pathology MH - Umbilical Cord/*cytology OTO - NOTNLM OT - UC-MSCs OT - Umbilical cord mesenchymal stem cells OT - high intraocular pressure OT - neuroprotection OT - ocular hypertension OT - retinal ganglion cells EDAT- 2018/03/06 06:00 MHDA- 2019/05/17 06:00 CRDT- 2018/03/06 06:00 PHST- 2018/03/06 06:00 [pubmed] PHST- 2019/05/17 06:00 [medline] PHST- 2018/03/06 06:00 [entrez] AID - 10.1080/02713683.2018.1440604 [doi] PST - ppublish SO - Curr Eye Res. 2018 Jun;43(6):810-820. doi: 10.1080/02713683.2018.1440604. Epub 2018 Mar 5.