Abstract
Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly worldwide. So far, the etiology and the progression of AMD are not well known. Animal models have been developed to study the mechanisms involved in AMD; however, according to the “Three Rs” principle, alternative methods have been investigated. Here we present a strategy to develop a “Three Rs” compliant retinal three-dimensional (3D) in vitro model, including a Bruch’s membrane model and retina pigment epithelium (RPE) layer. First, tensile testing was performed on porcine retina to set a reference for the in vitro model. The results of tensile testing showed a short linear region followed by a plastic region with peaks. Then, Bruch’s membrane (BrM) was fabricated via electrospinning by using Bombyx mori silk fibroin (BMSF) and polycaprolactone (PCL). The BrM properties and ARPE-19 cell responses to BrM substrates were investigated. The BrM model displayed a thickness of 44 µm, with a high porosity and an average fiber diameter of 1217 ± 101 nm. ARPE-19 cells adhered and spread on the BMSF/PCL electrospun membranes. In conclusion, we are developing a novel 3D in vitro retinal model towards the replacement of animal models in AMD studies.
Highlights
We have first characterized the biomechanical behavior of the retina to build a “Three Rs”-compliant in vitro retinal model with the same mechanical properties as the native tissue
Our findings have shown that the native retina presents a short elastic phase and a remarkably broad plastic phase with irreversible deformation
We highlighted the importance of the inclusion of a Bruch’s membrane (BrM) model in the in vitro retinal model to obtain a functional retinal pigment epithelium (RPE) monolayer and to better replicate Age-related macular degeneration (AMD) pathology
Summary
Even though anti-VEGF-based treatments have been demonstrated to halve the rate of blindness slowing down the progression of the wet AMD, they are expensive, represent a significant burden to patients and caregivers, and do not address the underlying disease processes, nor restore tissue functionality [4]. This relates to the fact that AMD is a complex, multifactorial, and heterogenous disease, with both environmental and genetic risk associations, and we still do not fully understand the pathogenic mechanisms involved in AMD [5]. It is fundamental to study and acquire greater insight into the underlying pathways involved in this disease to foresee novel treatments on the horizon
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