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Design and development of a novel artificial Bruch's membrane for ocular-based therapies

Design and development of a novel artificial Bruch's membrane for ocular-based therapies
Design and development of a novel artificial Bruch's membrane for ocular-based therapies
Age-related macular degeneration is a complex disorder causing irreversible loss of central vision in nearly 50 million individuals globally. The underlying pathology of this degenerative disorder is poorly understood, but impairment of the retinal pigment epithelium (RPE) layer and its supportive structure, the Bruch’s membrane (BrM), are considered to be of critical importance to disease onset and progression.

Although the less common form of this disease (neovascular or wet AMD) can be managed in most patients, the prevalent geographic or dry form of AMD has no treatment. Consequently, several therapeutic strategies are being persued to develop a long-lasting and effective treatment. Replacement of the damaged RPE and BrM offers the simplest form of therapy that has the potential to bring about the most rapid patient benefits. Studies along these lines have sought to directly inject RPE cell suspensions into rodent disease models. However, this has resulted in reflux of cells from the site of injection or misformed grafts.

Such issues may be circumvented by creating a biocompatible prosthetic BrM, onto which a monolayer of RPE cells can be grown, and then transplanted sub-retinally. Hence, methyl methacrylate and poly(ethylene glycol) methacrylate, two compounds approved for safe clinical applications, were previously used in our laboratory to create an artificial electrospun BrM scaffold.

In this project, the biophysical properties of this first generation BrM scaffold have been refined, such that its thickness, tensile strength, diffusional characteristics and surface properties were more akin to native BrM. Its suitability has been tested by culturing primary mouse RPE cells for long periods. These findings indicated that RPE grown on this novel synthetic BrM scaffold formed stable monolayers and expressed cell-specific markers, adopting structural as well as functional specialisations observed in the native RPE.

A further modification to this scaffold using anthracene resulted in a BrM mimic that had an improved biophysical characteristic, with initial subretinal transplantation experiments carried out by clinical colleagues indicating that this artificial scaffold can potentially act as a promising BrM replacement for AMD patients, as well as those suffering from rare conditions such as retinitis pigmentosa.
University of Southampton
Ward, Gareth
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Ward, Gareth
250b5aa5-a94a-49ec-9569-9250d8e2607b
Lotery, Andrew
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Cree, Angela
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Grossel, Martin
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Ratnayaka, Janaka
002499b8-1a9f-45b6-9539-5ac145799dfd

Ward, Gareth (2016) Design and development of a novel artificial Bruch's membrane for ocular-based therapies. University of Southampton, Doctoral Thesis, 272pp.

Record type: Thesis (Doctoral)

Abstract

Age-related macular degeneration is a complex disorder causing irreversible loss of central vision in nearly 50 million individuals globally. The underlying pathology of this degenerative disorder is poorly understood, but impairment of the retinal pigment epithelium (RPE) layer and its supportive structure, the Bruch’s membrane (BrM), are considered to be of critical importance to disease onset and progression.

Although the less common form of this disease (neovascular or wet AMD) can be managed in most patients, the prevalent geographic or dry form of AMD has no treatment. Consequently, several therapeutic strategies are being persued to develop a long-lasting and effective treatment. Replacement of the damaged RPE and BrM offers the simplest form of therapy that has the potential to bring about the most rapid patient benefits. Studies along these lines have sought to directly inject RPE cell suspensions into rodent disease models. However, this has resulted in reflux of cells from the site of injection or misformed grafts.

Such issues may be circumvented by creating a biocompatible prosthetic BrM, onto which a monolayer of RPE cells can be grown, and then transplanted sub-retinally. Hence, methyl methacrylate and poly(ethylene glycol) methacrylate, two compounds approved for safe clinical applications, were previously used in our laboratory to create an artificial electrospun BrM scaffold.

In this project, the biophysical properties of this first generation BrM scaffold have been refined, such that its thickness, tensile strength, diffusional characteristics and surface properties were more akin to native BrM. Its suitability has been tested by culturing primary mouse RPE cells for long periods. These findings indicated that RPE grown on this novel synthetic BrM scaffold formed stable monolayers and expressed cell-specific markers, adopting structural as well as functional specialisations observed in the native RPE.

A further modification to this scaffold using anthracene resulted in a BrM mimic that had an improved biophysical characteristic, with initial subretinal transplantation experiments carried out by clinical colleagues indicating that this artificial scaffold can potentially act as a promising BrM replacement for AMD patients, as well as those suffering from rare conditions such as retinitis pigmentosa.

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Published date: May 2016

Identifiers

Local EPrints ID: 434953
URI: https://eprints.soton.ac.uk/id/eprint/434953
PURE UUID: b75db835-f758-414f-9414-fb02f28bd5d6
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for Martin Grossel: ORCID iD orcid.org/0000-0001-7469-6854
ORCID for Janaka Ratnayaka: ORCID iD orcid.org/0000-0002-1027-6938

Catalogue record

Date deposited: 17 Oct 2019 16:30
Last modified: 18 Oct 2019 00:38

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