Understanding wet age-related macular degeneration: an organ-on-a-chip model of the outer blood-retinal barrier

Research output: ThesisPhD Thesis - Research UT, graduation UT

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Abstract

Visual impairment significantly affects life quality of patients, rendering them unable to perform simple everyday tasks. Visual impairment and blindness are already major direct and indirect burdens on healthcare which is expected to increase in the coming decades. Among blindness, age related macular degeneration (AMD) is currently the most common cause of blindness in elderly in western societies. The key tissue that is affected in AMD is the macula, which is a specialized region in the retina with the highest metabolic demands. Due to this, it is prone to dysfunction through decades of aging. It is not certain which series of exact events lead to the initiation and progression of AMD. However, it is multi-factorial where genetic and environmental factors are in play. Its most aggressive form, wet-AMD, is characterized by choroidal neovascularization (CNV), in which new blood vessels invade the normal tissue barriers of the outer retina from the underlying choroidal blood vessels. These vessels easily hemorrhage and eventually leak their contents below and within the retina, which leads to degeneration of photoreceptors in the macula. To better understand the disease pathology of AMD, experimental models are required in which the morphological changes of the tissues can easily be observed and experimental conditions can be readily manipulated.
In recent decades, thanks to microfluidics and microfabrication technologies, in vitro modelling platforms evolved into organ-on-a-chip (OOC) devices. These devices comprise individually perfused microchannels inhabited by living cells to create a realistic simulation of a tissue or organ of interest. This thesis demonstrates that OOCs may offer unique opportunities to model AMD and to study new potential treatments for this debilitating disease. This thesis provides a model of the outer blood retinal barrier in an organ-on-a-chip (OOC) device for investigation of age related macular degeneration (AMD). Mimicking pathophysiology of AMD is in particular challenging, as visible symptoms could be experienced after many decades of continuous stress on retinal tissues. Although vessel growth is the characteristic trait of wet-AMD, permeability increase is the main reason behind vision loss. Therefore, in this thesis we focused on this rather earlier event in disease pathology.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Twente
Supervisors/Advisors
  • van den Berg, Albert, Supervisor
  • Passier, P.C.J.J., Supervisor
  • van der Meer, A.D., Co-Supervisor
Award date16 Apr 2021
Place of PublicationEnschede
Publisher
Print ISBNs978-90-365-5167-0
DOIs
Publication statusPublished - 16 Apr 2021

Keywords

  • Organ-on-a-chip
  • blood-retinal barrier
  • age-related macular degeneration
  • permeability

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