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, Shih Jen Chen*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

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 nonmodified 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 PDMSPmL 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.

Original languageEnglish
Pages (from-to)64631-64648
Number of pages18
JournalOncotarget
Volume7
Issue number40
DOIs
StatePublished - 1 Jan 2016

Keywords

  • Age-related macular degeneration
  • Biomimetic scaffold
  • Pathology Section
  • Pigment epithelium cells
  • Pigment epithelium-derived factor
  • Pluripotent stem cells

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    Peng, C. H., Chuang, J. H., Wang, M. L., Jhan, Y. Y., Chien, K. H., Chung, Y. C., Hung, K. H., Chang, C-C., Lee, C. K., Tseng, W. L., Hwang, D. K., Hsu, C. H., Lin, T. C., Chiou, S. H., & Chen, S. J. (2016). Laminin modification subretinal bio-scaffold remodels retinal pigment epithelium-driven microenvironment in vitro and in vivo. Oncotarget, 7(40), 64631-64648. https://doi.org/10.18632/oncotarget.11502