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.
Highlights
Age-related macular degeneration (AMD) is a worldwide leading cause of blindness especially in developing countries [1]
To examine the phagocytosis function of the differentiated retinal pigment epithelial cells (dRPEs) cells, we incubated dRPE cells with the pH-sensitive pHrodoTM E. coli fluorescent bioparticles to visualize the engulfment of phagosomes
The results showed that both dRPE cells and ARPE-19 retinal pigment epithelium (RPE) cell line formed a hexagonal monolayer on PDMS-PmL but less homogenous on PDMS-Pm (O2 plasma only without laminin-coating), while both cells had difficulty to attach on the non-modified PDMS (Figure 3C)
Summary
Age-related macular degeneration (AMD) is a worldwide leading cause of blindness especially in developing countries [1]. Patients with end-stage AMD lost their central vision permanently mainly due to fibrovascular scar or atrophy of retinal pigment epithelium (RPE) and photoreceptors in macula [1, 2]. Current treatments focused on controlling growth and leakage of choroidal neovessels in wet-type AMD by injecting antivascular endothelial growth factor (VEGF) repeatedly [3]. The visual outcomes were usually restricted due to persistence of the fibrous tissue and the loss of RPE and photoreceptors [1, 4]. Scarce treatments focused their effect on RPE and neurosensory retina, or reconstructing the integrity of subretinal environment, of which the dysfunction and degeneration may weaken the blood-retina-barrier and cause AMD originally
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