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Shen Nian, Zhongjie Fu, Carl Sheridan, Victoria Kearns, Rachel Williams, Sai Hung David Wong, Krasimir Vasilev, Akash Bachhuka, Amy Lo, Wico Lai; In vivo Evaluation of Surface Modified Expanded-polytetrafluroethylene (ePTFE) Substrate as a Permanent Substrate for Cell Transplantation. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4085.
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Age-related macular degeneration (AMD) is the leading cause of severe and permanent visual loss in patients above 55 years of age with no effective treatments. Transplantation of a functional cell monolayer grown on the substrate into the subretinal space may help rescue the photoreceptors and in turn treating AMD. However, degradation of biodegradable substrates may cause the breakdown of functional cell monolayer and produce toxic byproducts. Therefore, synthetic non-degradable materials have been employed as the permanent underlying substrate to establish an intact functional cell monolayer for subretinal transplantation. We aimed to investigate the host response of surface modified ePTFE substrates after subretinal transplantation.
Fibronectin coated n-heptylamine modified (F-HA) ePTFE substrate was transplanted into the subretinal space of 4-week-old Royal College of Surgeons (RCS) rat eyes. Fundus was photographed and intraocular pressure (IOP) was measured immediately before and after surgery and weekly thereafter until RCS rats were sacrificed. 1 and 4 weeks after surgery, eyes were isolated and examined by H&E-stained retinal sections. Inflammatory responses were evaluated by immunostaining of tumor necrosis factor α (TNFα) and interleukin-1β (IL1β). Glial cell responses were assessed by immunostaining of glial fibrillary acidic protein (GFAP).
Retinal detachment was only observed immediately after surgery in fundus photos. IOP of rat eyes remained at about 10 mmHg except a drop to 7 mmHg immediately after transplantation. Retinal morphology was similar with/without substrate transplantation. Expression of pro-inflammatory cytokines (TNFα and IL1β) and GFAP was not significantly increased in the F-HA ePTFE substrate-transplanted eyes at 1 and 4 weeks. The F-HA ePTFE substrates remained flat beneath the neural retina up to 4 weeks after transplantation. Some cells were found to attach to F-HA ePTFE substrates and were positively stained with isolectin but negatively with RPE65.
F-HA ePTFE substrate showed good biocompatibility and lack of host inflammatory and glial cell responses, suggesting that it is a suitable permanent underlying substrate for subretinal transplantation.
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