title: Laminin modification subretinal bio-scaffold remodels retinal pigment epithelium-driven microenvironment in vitro and in vivo.
abstract: Advanced age-related macular degeneration (AMD) may lead to geographic atrophy or fibrovascular scar at macular, dysfunctional retinal microenvironment, and cause profound visual loss. Recent clinical trials have implied the potential application of pluripotent cell-differentiated retinal pigment epithelial cells (dRPEs) and membranous scaffolds implantation in repairing the degenerated retina in AMD. However, the efficacy of implanted membrane in immobilization and supporting the viability and functions of dRPEs, as well as maintaining the retinal microenvironment is still unclear. Herein we generated a biomimetic scaffold mimicking subretinal Bruch's basement from plasma modified polydimethylsiloxane (PDMS) sheet with laminin coating (PDMS-PmL), and investigated its potential functions to provide a subretinal environment for dRPE-monolayer grown on it. Firstly, compared to non-modified PDMS, PDMS-PmL enhanced the attachment, proliferation, polarization, and maturation of dRPEs. Second, PDMS-PmL increased the polarized tight junction, PEDF secretion, melanosome pigment deposit, and phagocytotic-ability of dRPEs. Third, PDMS-PmL was able to carry a dRPEs/photoreceptor-precursors multilayer retina tissue. Finally, the in vivo subretinal implantation of PDMS-PmL in porcine eyes showed well-biocompatibility up to 2-year follow-up. Notably, multifocal ERGs at 2-year follow-up revealed well preservation of macular function in PDMS-PmL, but not PDMS, transplanted porcine eyes. Trophic PEDF secretion of macular retina in PDMS-PmL group was also maintained to preserve retinal microenvironment in PDMS-PmL eyes at 2 year. Taken together, these data indicated that PDMS-PmL is able to sustain the physiological morphology and functions of polarized RPE monolayer, suggesting its potential of rescuing macular degeneration in vivo.
authors: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital & Fu-Jen Catholic University, Taipei Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Chi-Hsien
authors: CH
authors: Peng
authors: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors: Jen-Hua
authors: JH
authors: Chuang
authors: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Mong-Lien
authors: ML
authors: Wang
authors: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors: Yong-Yu
authors: YY
authors: Jhan
authors: Department of Ophthalmology, Tri-Service General Hospital & National Defense Medical Center, Taipei, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors: Ke-Hung
authors: KH
authors: Chien
authors: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Yu-Chien
authors: YC
authors: Chung
authors: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Kuo-Hsuan
authors: KH
authors: Hung
authors: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taipei, Taiwan.
authors: Chia-Ching
authors: CC
authors: Chang
authors: Department of Photonics, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors: Chao-Kuei
authors: CK
authors: Lee
authors: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors: Wei-Lien
authors: WL
authors: Tseng
authors: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: De-Kuang
authors: DK
authors: Hwang
authors: National Health Research Institute, Hsinchu, Taiwan.
authors: Chia-Hsien
authors: CH
authors: Hsu
authors: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Tai-Chi
authors: TC
authors: Lin
authors: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Shih-Hwa
authors: SH
authors: Chiou
authors: Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Shih-Jen
authors: SJ
authors: Chen
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry*; D016570:Bruch Membrane / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D048091:Guided Tissue Regeneration; D007797:Laminin / Q000737:chemistry*; D008268:Macular Degeneration / Q000601:surgery*; D020460:Melanosomes / Q000378:metabolism; D009757:Nylons / Q000737:chemistry*; D039904:Pluripotent Stem Cells / Q000473:pathology / Q000637:transplantation*; D055213:Retinal Pigment Epithelium / Q000473:pathology / Q000637:transplantation*; D033581:Stem Cell Transplantation; D013552:Swine; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D004129:Dimethylpolysiloxanes; D007797:Laminin; D009757:Nylons; C085707:poly(dimethylsiloxane)-polyamide copolymer
keywords: Pathology Section; age-related macular degeneration; biomimetic scaffold; pigment epithelium cells; pigment epithelium-derived factor; pluripotent stem cells