# Enhanced retinal pigment epithelial cells as a delivery vehicle for retinal disease

## TL;DR

This paper introduces a new method using engineered retinal pigment epithelial cells to deliver long-term treatment for age-related macular degeneration.

## Contribution

The novel approach uses iPS-derived RPE cells to stably produce therapeutic proteins for AMD treatment.

## Key findings

- Enhanced RPE cells produced high concentrations of aflibercept and sCD59.
- Sub-retinal injection of these cells prevented neovascular leakage in a mouse model of AMD.
- The method shows potential for long-term therapeutic delivery in retinal diseases.

## Abstract

Age-related macular degeneration (AMD) represents a major global health burden, with current estimates suggesting that up to 200 million people are affected globally. While effective treatments exist for the exudative form of the disease termed choroidal neovascular AMD, there remain challenges associated with long-term responses to treatment and the ongoing parallel development of the non-exudative form of AMD. Here, we sought to develop an approach for long-term delivery of both aflibercept, a decoy receptor that neutralises vascular endothelial growth factor and a concomitant treatment focused on treating the non-exudative form of AMD. To this end, we developed a series of induced pluripotent stem cell (iPS)-derived retinal pigment epithelial (RPE) cell lines that stably expressed aflibercept and/or sCD59. These cell lines were shown to produce high concentrations of both proteins. Sub-retinal injection of enhanced RPE cells potently prevented leakage of neovascular lesions in the JR5558 mouse model of retinal and choroidal neovascularization. Early results described here suggest that enhanced iPS-derived RPE cells could represent a novel approach to the long-term delivery of therapeutic agents to the eye.

AMD is one of the leading causes of central retinal blindness. Here, Campbell and colleagues show that transplanted RPE cells can be engineered to produce the therapeutic proteins aflibercept and sCD59, which can potently regulate disease progression in an animal model of AMD.