The Blood-Retinal Barrier: Structure and Functional Significance

Abstract

Formation and maintenance of the blood-retinal barrier is required for proper vision and loss of this barrier contributes to the pathology of a wide number of retinal diseases. The retina is responsible for converting visible light into the electrochemical signal interpreted by the brain as vision. Multiple cell types are required for this function, which are organized into eight distinct cell layers. These neural and glial cells gain metabolic support from a unique vascular structure that provides the necessary nutrients while minimizing interference with light sensing. In addition to the vascular contribution, the retina also possesses an epithelial barrier, the retinal pigment epithelium, which is located at the posterior of the eye and controls exchange of nutrients with the choroidal vessels. Together the vascular and epithelial components of the blood-retinal barrier maintain the specialized environment of the neural retina. Both the vascular endothelium and pigment epithelium possess a well-developed junctional complex that includes both adherens and tight junctions conferring a high degree of control of solute and fluid permeability. Understanding induction and regulation of the blood-retinal barrier will allow the development of therapies aimed at restoring the barrier when compromised in disease or allowing the specific transport of therapies across this barrier when needed. This chapter will highlight the anatomical structure of the blood-retinal barrier and explore the molecular structure of the tight junctions that provide the unique barrier properties of the blood--retinal barrier.

Course of Sodium Iodate–Induced Retinal Degeneration in Albino and Pigmented Mice

“…This damage may affect the function of the outer blood-retinal barrier between the fenestrated choriocapillaris and the photoreceptor layer and its ability to regulate and maintain normal ionic and metabolic gradients required for proper vision. 39 Disintegration and dysfunction of RPE cells decreases absorption of fluid from the subretinal space and may lead to enhanced diffusion of proteins across the paracellular space from the choriocapillaris into the subretinal space. 40 Notably, similar findings were recently observed in an SI-induced model in which higher doses and the IV administration mode were used and were also observed when mRNA levels were assessed.…”

RPE barrier breakdown in diabetic retinopathy: seeing is believing

“…While the breakdown of the endothelial barrier in DR has been investigated extensively, the concept of RPE barrier breakdown in the disease has not been widely acknowledged. As the blood content leaked through the RPE barrier causes excessive water influx to the retina, the breakdown of the RPE barrier is likely to play a causative role in the development of some forms of diabetic macular edema (DME), a major cause of vision loss in DR. As two detailed reviews about the RPE barrier and tight junctions were published early this year [11,12], the focus of this article will be on the regulation, function, and analysis of the RPE barrier in diabetes, particularly those related to tight junctions. In this article, we will discuss the clinical evidences of the diabetes-induced RPE barrier breakdown, the alteration of the RPE in diabetes, the molecular and cellular mechanisms of RPE barrier breakdown, and the research tools for the analysis of RPE barrier leakage.…”

Klebsiella pneumoniae Induces an Inflammatory Response in an In Vitro Model of Blood-Retinal Barrier

“…An early diagnosis and aggressive antibiotic therapy can improve the final course, but the visual outcome still remains poor (37). The entry of circulating bacteria into the retina requires crossing the BRB, composed of retinal microvascular EC which have a dynamic interaction with other neighboring cells, these being BRPC, astrocytes, and Müller cells (21,22). Despite the fact that the BRPC are morphologically situated closest to BREC, with which they share a basement membrane, they have been the subject of very few studies for testing the molecular mechanisms of bacterial invasion.…”

“…The retinal continuous endothelium forms the main structure of the BRB and rests on a basal lamina that is covered by the processes of astrocytes, Müller cells, and pericytes (blood-retinal pericytes [BRPC]s); the latter are encased in the basal lamina, in close contact with the blood retinal endothelial cells (BREC). BRPC, astrocytes, and Müller cells are considered to influence the activity of the BREC and BRB by transmitting regulatory signals to BREC, indicating changes in the microenvironment of the retinal neuronal circuitry (21). In particular, BRPC are uniquely positioned within the microvessels to serve as vital integrators, coordinators, and effectors of many neurovascular functions, including angiogenesis, barrier formation and maintenance, vascular stability, angioarchitecture, and regulation of capillary blood flow (22).…”