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Pathophysiology of leakage and the special role of vascular abnormalities in DME
Author(s) -
Schlingemann Reinier
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.8268
Subject(s) - paracellular transport , vascular permeability , transcellular , blood–retinal barrier , retinal , vascular endothelial growth factor , tight junction , basal lamina , endothelium , medicine , microbiology and biotechnology , endothelial stem cell , pathology , biology , diabetic retinopathy , ophthalmology , endocrinology , permeability (electromagnetism) , biochemistry , ultrastructure , in vitro , diabetes mellitus , membrane , vegf receptors
Breakdown of the inner endothelial blood‐retinal barrier (BRB) in diabetic retinopathy and retinal vein occlusions results in vasogenic edema and neural tissue damage, causing loss of vision. The understanding of the complex cellular and molecular processes involved in BRB leakage has grown rapidly in recent years. Altered BRB function is caused by a change in the permeability characteristics of retinal endothelial cells induced by growth factors such as vascular endothelial growth factor (VEGF) and cytokines. This leads to increased paracellular and transcellular transport across the retinal vascular wall via opening of endothelial intercellular junctions and qualitative and quantitative changes in endothelial caveolar transcellular transport, respectively. Functional changes in pericytes and astrocytes, as well as structural changes in the composition of the endothelial glycocalyx and the basal lamina around BRB endothelium further facilitate BRB leakage. As Starling's rules apply, active transcellular transport of plasma proteins by the BRB endothelial cells causing increased interstitial osmotic pressure is probably the main factor in the formation of macular edema. In addition to these active, regulated and reversible mechanisms of leakage, long standing retinal vascular disease such as diabetic macular edema and retinal vein occlusion may also lead to the formation of vascular abnormalities in the form of telangiectatic capillaries (TelCaps). These are characterized by chronic uncontrolled leakage associated with formation of hard exudates, which may be independent of VEGF and require other forms of treatment such as laser photocoagulation instead of VEGF inhibitors or corticosteroids.