Description
Cerebral blood vessels play a central role in supplying and regulating the disproportionately large amount of energy the brain requires for neurological function. They also protect the central nervous system by forming the blood-brain barrier (BBB), which shields neurons from pathogens and immune attack. This intimate functional interdependency between neurons and their associated blood vessels is referred to as the neurovascular unit (NVU). Dysfunction of the NVU underlies many neurological diseases and has been recognised by the American Heart and Stroke Associations as central to understanding and effectively treating conditions as wide-ranging as stroke, multiple sclerosis, and Alzheimer's disease. An analogous structure exists in the retina, where the NVU forms the blood-retinal barrier (BRB), and its dysfunction frequently contributes to neuronal morbidity and vision loss.
Cell culture models are instrumental for interrogating NVU function, particularly its barrier properties. However, models specific to the retinal NVU do not currently exist. Retinal paradigms are instead inferred from the many models developed for the BBB and cerebral NVU, despite well-established differences between the two systems. For instance, retinal blood vessels exhibit distinct pericyte coverage ratios and interact with retina-specific glial cells rather than the astrocytes that predominate at the BBB.
To address this gap, we are establishing cell culture models specifically tailored to the retinal NVU. We used a combination of established cell lines and primary cells isolated from porcine and rodent brain and retina, including endothelial cells, pericytes, Müller cells, and retinal ganglion cells. These cell types are characterised individually and then integrated into co-culture and tri-culture configurations to recapitulate the multicellular architecture and intercellular signalling of the retinal NVU in vivo. Barrier function is assessed using transendothelial electrical resistance (TEER) and permeability assays, alongside immunofluorescence of tight junction proteins and cell-type-specific markers.
This study contributes to a better understanding of how the retinal NVU differs from that found in the brain and facilitates future approaches to study NVU dysfunction associated with widespread blinding diseases such as diabetic retinopathy.
Lay Abstract
The brain and the retina are among the most energy-demanding tissues in the body. To function properly, both rely on a tightly regulated partnership between nerve cells and the blood vessels that supply them. This partnership, known as the neurovascular unit, does more than deliver nutrients; it also forms a protective barrier that prevents harmful substances from entering the nervous system. When this barrier breaks down, it contributes to serious conditions, including stroke, Alzheimer’s disease, and blinding disorders such as diabetic retinopathy.
Researchers currently study this barrier using laboratory cell models, but a key gap remains: models designed specifically for the retina are not yet available. Instead, researchers rely on models developed for the brain, even though the retina contains distinct cell types and differs from brain tissue in important ways.
Our project aims to fill this gap by establishing a representative laboratory model of the retinal neurovascular unit. To achieve this, we culture retinal cells, including vascular cells, supporting cells, and neurons, and combine them to closely mimic their interactions in the living eye. This approach will provide researchers with a more accurate tool for understanding and ultimately treating diseases that lead to vision loss.
| Lay Title | Rebuilding the retina in a dish to understand vision loss |
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| Role | Postdoctoral Researcher |