Blood‐Ocular Barriers and Macular Edema

Abstract The blood‐ocular barrier system is formed by two main barriers: the blood‐aqueous barrier (BAB) and the blood‐retinal barrier (BRB). Homeostasis in the retina microenvironment is maintained by the function of the BRB which regulates the movement of chemicals and cells between the intravascular compartment and the retina. The BRB consists of two major topographically distinct components: the endothelium of the retinal vessels (inner BRB) and the retinal pigment epithelium (outer BRB). The barrier function of the retinal vascular endothelium depends on its continuous epithelial‐like arrangement with the endothelial cells united by tight junctions, whereas the ability of the retinal pigment epithelium to regulate solute transport depends on the apical tight junctions between these cells. The tight junctions are membrane fusion areas between adjacent cells that serve as a diffusion barrier for paracellular transport and as a “molecular fence”, restricting the free movement of transmembrane proteins, and thus maintaining cell polarity and the asymmetric distribution of transmembrane proteins. Among the most important proteins that are associated with tight junctions are occludin, zonula occludens and claudins. Pathologic increase in blood retinal permeability can be caused by endothelial damage, tight junction disassembly, or cytokines such as vascular endothelial growth factor. Several methods have been developed to allow detection, quantification and monitoring of BRB breakdown in experimental and clinical settings. In humans, fluorescein angiography, vitreous fluorophotometry and OCT are the most commonly used. Alterations of the BRB play a crucial role in the development of retinal edema. Macular edema is the result of an accumulation of fluid in the retinal layers around the fovea, contributing to vision loss by altering the functional relationship in the retina and promoting an inflammatory reparative response. The accumulation of fluid is directly associated with an alteration of the BRB. In this situation the protective effect of the BRB is lost and Starling’s law applies.