The macula is the area in the retina that is responsible for high-resolution, central vision. Age-related macular degeneration (AMD) is currently the leading cause of vision loss in Western society.
The most aggressive form, exudative or “wet”-AMD, is characterized by fluid leakage and growth of blood vessels into the retina. These dysfunctional vessels are part of the choriocapillary bed and their leakage and growth eventually lead to damage to the retinal pigment epithelium and the intermediate Bruch’s membrane. This then leads to the progressive degeneration of the photoreceptors and loss of central vision. For patients, quality of life is severely affected, as simple tasks such as ability to read, drive, recognize faces etc. are impaired or lost.
In order to investigate AMD, cellular and animal models have been developed. Although commonly used, these models suffer from specific issues. Cellular models involving Transwell cultures of single or co-cultures with choroidal endothelial and retinal pigment epithelial cells do not fully mimic the physiology of the eye. Rodent models are disadvantageous due to the lack of a macula and interspecies anatomical differences. Non-human primates are more realistic models, but the time required for the disease progression, the cost, and the ethical issues make primate models less suitable for AMD research.
In the last decade, organ-on-a-chip technology has emerged as a solution to these challenges. These microfluidic cell culture devices contain continually perfused microchannels that are inhabited by living cells to form tissues that exhibit organ-level physiology. In addition to the simplest systems, which consists of a single perfused microfluidic chamber and one kind of cultured cell, more complex devices exist with two or more microchannels that are connected by porous membranes lined by cells which then create the interface between different tissues. These systems not only incorporate physical forces (i.e. fluid shear stress, cyclic strain, and mechanical compression etc.) but also permit analysis of organ-specific responses (i.e. including recruitment of circulating immune cells, reaction to drugs, toxins etc.).
The goal of this project is to study if anti-inflammatory treatment can halt the progression of wet-AMD by normalizing the permeability of blood vessel walls. Using organ-on-a-chip technology, a realistic model of the retinal vasculature, containing human endothelial tissue and retinal cells will be developed to investigate the effects of the treatment. We will use this model to simulate the conditions of wet-AMD, measure the permeability of the cultured blood vessels, and evaluate the resulting damage and recovery to cultured retinal tissue both in the presence and absence of inflammatory and anti-inflammatory stimuli.
The project is carried out in collaboration with the Laboratory of Translational Immunology of the University Medical Center Utrecht as well as with the Department of Ophthalmology of the Radboud University Medical Center.
This project is supported by Stichting TWIN, The Netherlands.
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