Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane

Abstract

Age-related macular degeneration (AMD) is the leading cause of legal blindness in older people in the developed world. The disease involves damage to the part of the retina responsible for central vision. Degeneration of retinal pigment epithelial (RPE) cells, photoreceptors, and choriocapillaris may contribute to visual loss. Over the past decades, scientists and clinicians have tried to replace lost RPE cells in patients with AMD using cells from different sources. In recent years, advances in generating RPE cells from stem cells have been made and clinical trials are currently evaluating the safety and efficiency of replacing the degenerated RPE cell layer with stem cellderived RPE cells. However, the therapeutic success of transplantation of stem cellderived RPE cells may be limited unless the transplanted cells can adhere and survive in the long term in the diseased eye. One hallmark of AMD is the altered extracellular environment of Bruch's membrane to which the grafted cells have to adhere. Here, we discuss recent approaches to overcome the inhibitory environment of the diseased eye and to enhance the survival rate of transplanted RPE cells. Our aim is to highlight novel approaches that may have the potential to improve the efficacy of RPE transplantation for AMD in the future.

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

“…by up to 3 weeks), but using an aged Bruch's membrane also hinders the formation of functional monolayers (Sugino et al, 2011). Multiple methods to enhance RPE adhesion to Bruch's membrane are reviewed by Heller and Martin (Heller and Martin, 2014). Of these, manipulating RPE cells to overexpress integrin family molecules in order to improve the binding and proliferation of RPE cells on Bruch's membrane seems most promising (Fang et al, 2009;Afshari et al, 2010).…”

Immunochemical analysis of the integrin expression in retinal pigment epithelial cells

“…For instance, on RPE cells, they mediate the interaction with Bruch's membrane and the phagocytosis of shed POS [1,3,5]. In this study we analyzed and compared the expression of integrin subunits in different RPE cells using immunostaining.…”

“…Integrins are crucial for the proper functioning of the RPE cells. The adhesion of the RPE monolayer to its normal substrate, Bruch's membrane, is mediated via integrins [4,5]. Additionally, αVβ5 integrin is essential for POS binding and subsequent phagocytosis through CD36 and the protooncogene tyrosine-protein kinase MER (MERTK) [3,[6][7][8][9].…”

Retinal Degenerative Diseases

“…A variety of stem cell types for use as AMD therapeutics have been developed in recent years (Evans and Syed 2013;Melville et al 2013;Heller and Martin 2014). Most recently a phase I/II clinical trial involving the transplantation of human embryonic stem cell-derived RPE stem cells into the subretinal space of patients with dry AMD showed improvement in vision .…”