Towards an In Vitro Retinal Model to Study and Develop New Therapies for Age-Related Macular Degeneration

Area of Science:

• Biomedical Engineering
• Ophthalmology
• Tissue Engineering

Background:

• Age-related macular degeneration (AMD) is a primary cause of vision loss in older adults globally.
• The exact causes and progression of AMD remain incompletely understood.
• Current research often relies on animal models, prompting a need for ethically compliant alternatives.

Purpose of the Study:

• To develop a novel,
• Three Rs
• compliant three-dimensional (3D) in vitro retinal model for studying AMD.
• To create a functional Bruch's membrane (BrM) and retinal pigment epithelium (RPE) layer model.

Main Methods:

• Tensile testing was performed on porcine retina to establish mechanical benchmarks.
• Bruch's membrane (BrM) was fabricated using electrospinning with Bombyx mori silk fibroin (BMSF) and polycaprolactone (PCL).
• Characterization of the BrM model's properties and assessment of ARPE-19 cell response to the fabricated substrates.

Main Results:

• Porcine retina tensile testing revealed distinct linear and plastic deformation regions.
• The electrospun BrM model exhibited a thickness of 44 µm, high porosity, and an average fiber diameter of 1217 ± 101 nm.
• ARPE-19 cells demonstrated successful adhesion and spreading on the BMSF/PCL electrospun membranes.

Conclusions:

• A promising 3D in vitro retinal model, incorporating a BrM and RPE layer, has been successfully developed.
• This novel model shows potential for replacing traditional animal models in AMD research.
• The fabricated BrM model supports RPE cell behavior, indicating its suitability for AMD mechanism studies.