Oncotarget

Research Papers: Pathology:

Laminin modification subretinal bio-scaffold remodels retinal pigment epithelium-driven microenvironment in vitro and in vivo

Chi-Hsien Peng, Jen-Hua Chuang, Mong-Lien Wang, Yong-Yu Jhan, Ke-Hung Chien, Yu-Chien Chung, Kuo-Hsuan Hung, Chia-Ching Chang, Chao-Kuei Lee, Wei-Lien Tseng, De-Kuang Hwang, Chia-Hsien Hsu, Tai-Chi Lin, Shih-Hwa Chiou and Shih-Jen Chen _

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Oncotarget. 2016; 7:64631-64648. https://doi.org/10.18632/oncotarget.11502

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Abstract

Chi-Hsien Peng1,3,8,*, Jen-Hua Chuang2,9,*, Mong-Lien Wang2,10,*, Yong-Yu Jhan1,9, Ke-Hung Chien4,9, Yu-Chien Chung1,10, Kuo-Hsuan Hung1,8,10, Chia-Ching Chang5, Chao-Kuei Lee6, Wei-Lien Tseng2,9, De-Kuang Hwang1,10, Chia-Hsien Hsu7, Tai-Chi Lin1,8, Shih-Hwa Chiou1,2,8,9,10 and Shih-Jen Chen1,10

1 Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan

2 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

3 Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital & Fu-Jen Catholic University, Taipei Taiwan

4 Department of Ophthalmology, Tri-Service General Hospital & National Defense Medical Center, Taipei, Taiwan

5 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taipei, Taiwan

6 Department of Photonics, National Sun Yat-sen University, Kaohsiung, Taiwan

7 National Health Research Institute, Hsinchu, Taiwan

8 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

9 Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan

10 School of Medicine, National Yang-Ming University, Taipei, Taiwan

* These authors have equally contributed to this work

Correspondence to:

Shih-Jen Chen, email:

Keywords: age-related macular degeneration, biomimetic scaffold, pluripotent stem cells, pigment epithelium cells, pigment epithelium-derived factor, Pathology Section

Received: May 13, 2016 Accepted: July 19, 2016 Published: August 22, 2016

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.


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