title: Human retinal progenitor cell transplantation preserves vision.
abstract: Cell transplantation is a potential therapeutic strategy for retinal degenerative diseases involving the loss of photoreceptors. However, it faces challenges to clinical translation due to safety concerns and a limited supply of cells. Human retinal progenitor cells (hRPCs) from fetal neural retina are expandable in vitro and maintain an undifferentiated state. This study aimed to investigate the therapeutic potential of hRPCs transplanted into a Royal College of Surgeons (RCS) rat model of retinal degeneration. At 12 weeks, optokinetic response showed that hRPC-grafted eyes had significantly superior visual acuity compared with vehicle-treated eyes. Histological evaluation of outer nuclear layer (ONL) characteristics such as ONL thickness, spread distance, and cell count demonstrated a significantly greater preservation of the ONL in hRPC-treated eyes compared with both vehicle-treated and control eyes. The transplanted hRPCs arrested visual decline over time in the RCS rat and rescued retinal morphology, demonstrating their potential as a therapy for retinal diseases. We suggest that the preservation of visual acuity was likely achieved through host photoreceptor rescue. We found that hRPC transplantation into the subretinal space of RCS rats was well tolerated, with no adverse effects such as tumor formation noted at 12 weeks after treatment.
authors.affiliation: Department of Ophthalmology, Second Xiangya Hospital and International Academy of Translational Medicine, Central South University, Changsha, Hunan 410011, China; Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093.
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, Massachusetts 02114.
authors.forename: Petr
authors.initials: P
authors.lastname: Baranov
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093.
authors.forename: Sherrina
authors.initials: S
authors.lastname: Patel
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093.
authors.forename: Hong
authors.initials: H
authors.lastname: Ouyang
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093.
authors.forename: John
authors.initials: J
authors.lastname: Quach
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093.
authors.forename: Frances
authors.initials: F
authors.lastname: Wu
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093; Molecular Medicine Research Center, West China Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Austin
authors.initials: A
authors.lastname: Qiu
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093; Molecular Medicine Research Center, West China Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Hongrong
authors.initials: H
authors.lastname: Luo
authors.affiliation: ReNeuron Ltd., Guildford, Surrey GU2 7AF, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hicks
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093; Department of Ophthalmology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093; Molecular Medicine Research Center, West China Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093.
authors.forename: Nicole
authors.initials: N
authors.lastname: Sfeir
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093.
authors.forename: Cindy
authors.initials: C
authors.lastname: Wen
authors.affiliation: Molecular Medicine Research Center, West China Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Meixia
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Da Vinci Consulting, Los Angeles, California 90069.
authors.forename: Victoria
authors.initials: V
authors.lastname: Reade
authors.affiliation: Molecular Medicine Research Center, West China Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Sara
authors.initials: S
authors.lastname: Patel
authors.affiliation: Molecular Medicine Research Center, West China Hospital, Chengdu, Sichuan 610041, China.
authors.forename: John
authors.initials: J
authors.lastname: Sinden
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai 200080, China; Eye Research Institute, Shanghai JiaoTong University, Shanghai 200080, China. Electronic address: xdsun@sjtu.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093.
authors.forename: Peter
authors.initials: P
authors.lastname: Shaw
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, Massachusetts 02114.
authors.forename: Michael
authors.initials: M
authors.lastname: Young
authors.affiliation: Department of Ophthalmology, Second Xiangya Hospital and International Academy of Translational Medicine, Central South University, Changsha, Hunan 410011, China; Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, California 92093; Molecular Medicine Research Center, West China Hospital, Chengdu, Sichuan 610041, China; Veterans Affairs Healthcare System, San Diego, California 92161. Electronic address: kang.zhang@gmail.com.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005333:Fetus / Q000166:cytology; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000637:transplantation*; D051381:Rats; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000502:physiology; D012162:Retinal Degeneration / Q000503:physiopathology / Q000601:surgery*; D033581:Stem Cell Transplantation; D014792:Visual Acuity
keywords: Eye; Neuroprogenitor Cell; Retinal Degeneration; Retinal Progenitor Cells; Stem Cells; Transplantation