Subretinal application of cell cultures: Surgical methods and its transition to the use in human

Abstract

AbstractThe progression of age‐related macular degeneration (AMD) results in irreversible and untreatable impairment of central vision. The formation of the drusen and subsequent atrophy of in the retinal pigmented epithelium (RPE) with development of neovascular membranes remain the typical features of AMD pathogenesis. As the result of the disorganization of the RPE the death photoreceptor cell develops, which is associated with altered RPE phagocytosis, increased RPE permeability, formation of choroidal neovascularization, and involvement of resident and monocytic microglial cells. Nevertheless, the exact cause of the RPE degeneration is still not fully understood. Up to date there is no therapeutic approach, which could reverse the course of AMD progression. Injection of anti‐vascular endothelial growth factors (VEGFs), laser‐photo coagulation and photodynamic therapy of the neovascularisations are being widely used to treat the complications of exudative AMD and therefore to prevent visual loss. Since few decades, the concept of substitutional cell‐based regenerative treatment has been investigated by many groups. It could offer in the near future an alternative approach to restore impaired vision in AMD. Th studies have shown that subretinal implantation of RPE cells seeded on a biodegradable scaffold enhances the integration of the donor cells compared to the injection of cell‐suspension as method of delivery. This could improve the differentiation of donor RPE cells into the host retina and help with the proper cellularization of the RPE monolayer. However, the implantation techniques including surgical procedure with exposion of subretinal space and the development and use of delivery instruments remains challenging. Experimental studies with subretinal RPE transplantation are focused on development of optimal surgical techniques, which could be easily transferred to the application in humans. The cultivation and reproducible viability of hRPEs for transplantation purposes on biodegradable scaffolds for human transplantation shall correspond and be adapted to the instrumentation used during the surgery. Hence, the advances in the methodology and the results of improved approaches shall be investigated further.