Assessment of Inner Blood–Retinal Barrier: Animal Models and Methods

Abstract

Proper functioning of the neural retina relies on the unique retinal environment regulated by the blood–retinal barrier (BRB), which restricts the passage of solutes, fluids, and toxic substances. BRB impairment occurs in many retinal vascular diseases and the breakdown of BRB significantly contributes to disease pathology. Understanding the different molecular constituents and signaling pathways involved in BRB development and maintenance is therefore crucial in developing treatment modalities. This review summarizes the major molecular signaling pathways involved in inner BRB (iBRB) formation and maintenance, and representative animal models of eye diseases with retinal vascular leakage. Studies on Wnt/β-catenin signaling are highlighted, which is critical for retinal and brain vascular angiogenesis and barriergenesis. Moreover, multiple in vivo and in vitro methods for the detection and analysis of vascular leakage are described, along with their advantages and limitations. These pre-clinical animal models and methods for assessing iBRB provide valuable experimental tools in delineating the molecular mechanisms of retinal vascular diseases and evaluating therapeutic drugs.

Neurovascular Relationships in AGEs-Based Models of Proliferative Diabetic Retinopathy

“…However, while MG reside within the neural retina, AC cell bodies are located upon the nerve fiber layer of healthy retina and extend only their cell processes within the neural retina [13]. Surprisingly, many barrier models include only AC to study the role of glia in different neurovascular barriers [14,15]. However, PDR patients often undergo vitrectomy to remove scarred tissue made of reactive astrocytes upon the nerve fiber layer [16], leaving pathogenic iBRB with strongly diminished numbers of AC and, consequently, stronger reliance on interactions between MG and EC.…”

Causal relationships between blood metabolites and diabetic retinopathy: a two-sample Mendelian randomization study

“…Thirdly, to explore additional blood metabolites associated with DR, we did not correct for P -value by false discovery rate correction, which can result in false positives in multiple tests. Fourthly, the direct pathological site of DR is the retina, and the blood-retinal barrier exhibits strict selectivity in the filtration of metabolites ( 64 ), indicating the need for further research to analyze changes in metabolites in vitreous and aqueous humor. Finally, it is worth noting that some metabolites in the metabolic profile of this study have unclear structures and functions, which limits our ability to interpret the results of the MR study.…”

New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases

“…68,[72][73][74][75] Besides these physiological processes, angiogenesis can also occur under pathological circumstances, for example in tumors 1,76,77 and in neovascular ocular diseases, such as proliferative diabetic retinopathy, exudative age-related macular degeneration, and retinopathy of the prematurity. [78][79][80][81][82][83][84] Both in tumors and in these eye conditions, angiogenesis usually does not occur as a single process, but invariably drives at least partly elements of the wound healing cascade, such as fibrin deposition, influx of immune cells, formation of myofibroblasts, and deposition of matrix components. [84][85][86][87][88][89][90] The growth of primary tumors and secondary metastases requires angiogenesis when the tumors reach a volume of approximately 1-2 mm 3 and diffusion of oxygen from existing blood vessels is not sufficient anymore.…”