Glucocorticoid regulation of endothelial cell tight junction gene expression: novel treatments for diabetic retinopathy.
Loss of blood-retinal barrier (BRB) integrity and vascular permeability characterizes diabetic retinopathy, and new therapies to reverse or prevent vascular permeability are needed to treat this debilitating disease. Glucocorticoids are currently under investigation for use as a local therapeutic treatment for diabetic retinopathy. This review examines the changes that occur to barrier properties in diabetic retinopathy and the potential to use glucocorticoids to restore vascular barrier properties in the retina. Glucocorticoids are useful in preserving the integrity of the blood-brain barrier in the treatment of brain tumors, and these steroids show similar effects on the retinal vasculature suggesting their potential usefulness in treating diabetic retinopathy. Recent progress has been made toward the goal of elucidating the precise mechanism underlying the protective effects of glucocorticoids on the retinal vasculature. Glucocorticoids may act by both suppressing inflammation and by directly affecting the endothelial cells by regulating phosphorylation, organization, and content of tight junction proteins. Further work will advance our understanding of glucocorticoid regulation of barrier properties allowing the ultimate goal of developing a specific and safe therapy to treat or prevent loss of the blood-neural barrier in a number of diseases, including brain tumors and diabetic retinopathy.
Felinski
Edward A
EA
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. efelinski@psu.edu
Antonetti
David A
DA
D000818:Animals; D001813:Blood-Retinal Barrier; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008269:Macular Edema / Q000188:drug therapy; D019108:Tight Junctions / Q000378:metabolism*
D005938:Glucocorticoids