Georgiadis, Odysseas; (2021) Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium Transplantation in Advanced Neovascular Age-Related Macular Degeneration. Doctoral thesis (M.D(Res)), UCL (University College London).

Preview

Text THESIS_Odysseas_Georgiadis.pdf Download (12MB) | Preview

Abstract

Age-related macular degeneration (AMD) remains one of the leading causes of permanent vision impairment worldwide. It is a disorder of the central retina that manifests with irreversible cell loss, primarily affecting the retinal pigment epithelium (RPE) and subsequently the retina and choroid, leading to blindness through atrophy or neovascularization and exudation. Current treatments are only able to suppress the progression of the early and moderate neovascular AMD, mainly by controlling leakage and haemorrhage, while there is no established therapy for the atrophic type or the advanced neovascular type. RPE transplantation strategies have been attempted with promising outcomes; however, their operational complexity combined with the large patients’ volume has underlined the need for more accessible cell sources and a more feasible surgical paradigm. This thesis aims to examine the feasibility, safety and efficacy of transplantation of a human Embryonic Stem Cell (hESC)-derived RPE sheet in patients with severe neovascular (n) AMD. A fully differentiated hESC-RPE monolayer on a coated synthetic basement membrane (BM) has been bioengineered ex vivo and, using a purpose-designed surgical tool, has been implanted in the subretinal space of two patients with nAMD and acute vision decline. Systemic immunosuppression was administered during the peri- operative periods, while only local, intra-ocular steroids were given for the longer term. The patients were followed-up in a prospective study to assess the safety, and the structural and functional outcomes of this strategy for two years post-operatively. Both subjects demonstrated good safety outcome with no signs of local or distal tumorigenicity or uncontrolled proliferation from the implanted cells. Both showed reconstruction of the RPE-BM complex sufficient to support the retinal structure and the rescue and preservation of the photoreceptors, during the study period. Furthermore, both patients showed significant gain in their visual function, in terms of fixation, retinal light sensitivity, visual acuity and reading speed, maintained for two years. Most importantly, in both cases there was a clear co-localisation of the structural support, provided by the transplant, with the areas of functional improvement. The work in this thesis provides proof that the reconstruction of the RPE using hESC on synthetic BM can rescue and preserve the retinal structure and function over the long term, in severe neovascular AMD.

Download activity - last month

Export as JSONXMLCSV

Download activity - last 12 months

Export as CSVJSONXML

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item