Developing cell replacement therapy for AMD using an artificial scaffolding for the cells
Research details
- Type of funding: Early Career Investigator Award
- Grant Holder: Dr Heather Thomson
- Institute: University of Southampton
- Region: South East
- Start date: May 2013
- End Date: August 2014
- Priority:
- Eye Category:
Overview
Age-related macular degeneration (AMD) is the most common cause of blindness in industrialised countries. There are 2 types: wet and dry. The dry form affects 9 in 10 people with AMD but there is no treatment yet.
In dry AMD, a layer of cells called the retinal pigment epithelium becomes damaged. These are the cells that provide supplies to the light-sensitive photoreceptor cells in the retina and so if they die, so do the photoreceptors.
A potential option for treatment is to replace the retinal pigment epithelial cells. However this hasn’t had too much success so far. The cells need to attach to a support matrix soon after being transplanted, otherwise they don’t survive. But AMD also affects the matrix (called Bruch’s membrane).
So in this project Dr Thompson is aiming to transplant cells grown from stem cells together with a plastic matrix as a scaffolding. If it works, it could be a useful approach for AMD and for other cell-replacement treatments for conditions that affect the retina.-
Scientific summary
Use of electrospun fibres as an artificial Bruch’s Membrane for retinal pigment epithelium cell
Age-related macular degeneration (AMD) is the leading cause of blindness in industrialised countries. With increasing longevity, prevalence is expected to double in the coming decades. There is currently no effective therapeutic option for the most predominant “dry” form of the disease.
Retinal pigment epithelium (RPE) cells support photoreceptor function. Therefore transplantation of RPE cells is a potential treatment for dry AMD.
RPE cells are anchorage dependent thus, to prevent cell death, they must quickly attach to an accommodating matrix following transplantation. Bruch’s membrane (BM) is the supportive structure upon which RPE cells normally attach. However in advanced forms of AMD the integrity of BM is compromised. Therefore delivery of RPE cells attached to a scaffold is of interest.
The team is producing electrospun polymer scaffolds using Poly(methyl methacrylate) (PMMA). Scaffolds are being modified with cell adhesion motifs to mimic the extracellular matrix environment of BM. The biocompatibility of these electrospun scaffolds is being assessed in vitro using RPE cells generated from induced pluripotent stem cells (IPSCs).
When the optimal scaffold which supports RPE survival and function has been identified, in vivo studies are being carried out. IPSC-derived RPE cells attached to electrospun polymer scaffolds will be transplanted into a mouse model of retinal degeneration. Measures of retinal structure (in vivo imaging, histology) and function (electroretinography, pupilometry) will be assessed. The researchers aim to show that artificial scaffolds can not only be used as a vehicle for RPE cell delivery but also as a permanent functional replacement for BM.