The blood–retina barrier in health and disease

• Published in: The FEBS journal Vol. 290; no. 4; pp. 878 - 891
• Main Authors: O’Leary, Fionn, Campbell, Matthew
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.02.2023
• Subjects: barrier; Blood; Blood circulation; Blood-Retinal Barrier - metabolism; Capillaries; Diabetes mellitus; Diabetic retinopathy; Edema; Endothelial cells; Endothelial Cells - metabolism; Epithelium; Eye diseases; Humans; Macular degeneration; Maintenance; Microenvironments; Microvasculature; Molecular structure; neurovascular; pathophysiology; Retina; Retina - metabolism; Retinal Diseases - metabolism; Retinal pigment epithelium; Retinal Pigment Epithelium - metabolism; Retinopathy; Structural integrity; Structure-function relationships; tight junction; tight junctions; neurovascular; barrier; retina; blood; tight junction
• DOI: 10.1111/febs.16330
• ISSN: 1742-464X; 1742-4658

The blood–retina barrier (BRB) is the term used to define the properties of the retinal capillaries and the retinal pigment epithelium (RPE), which separate the systemic circulation from the retina. More specifically, the inner blood–retina barrier (iBRB) is used to describe the properties of the endothelial cells that line the microvasculature of the inner retina, while the outer blood–retina barrier (oBRB) refers to the properties of the RPE cells that separate the fenestrated choriocapillaris from the retina. The BRB is not a fixed structure; rather, it is dynamic, with its components making unique contributions to its function and structural integrity, and therefore the retina. For example, while tight junction (TJ) proteins between retinal endothelial cells are the key molecular structures in the maintenance of the iBRB, other cell types surrounding endothelial cells are also important. In fact, this overall structure is termed the neurovascular unit (NVU). The integrity of the BRB is crucial in the maintenance of a ‘dry’, tightly regulated retinal microenvironment through the regulation of transcellular and paracellular transport. Specifically, breakdown of TJs can result in oedema formation, a hallmark feature of many retinal diseases. Here, we will describe the oBRB briefly, with a more in‐depth focus on the structure and function of the iBRB in health and diseased states. Finally, the contribution of the BRB to the pathophysiology of age‐related macular degeneration (AMD), diabetic retinopathy (DR) and other rarer retinal diseases will be discussed. The inner blood–retina barrier (iBRB) refers to the properties of endothelial cells associated with the blood vessels of the inner retina. These cells strictly regulate entry and exit from the retina and perturbations in their function have detrimental effects on vision and lead to conditions such as diabetic retinopathy (DR) and age‐related macular degeneration (AMD). This review provides a succinct overview of BRB breakdown‐associated retinal conditions and the putative underlying mechanisms of disease.