Investigative Ophthalmology & Visual Science, Vol 38, 2423-2427, Copyright © 1997 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Astrocytes increase barrier properties and ZO-1 expression in retinal vascular endothelial cells

TW Gardner, E Lieth, SA Khin, AJ Barber, DJ Bonsall, T Lesher, K Rice and WA Brennan Jr
Department of Ophthalmology, Penn State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA.

PURPOSE: Diabetic retinopathy and other diseases associated with retinal edema are characterized by increased microvascular leakage. Astrocytes have been proposed to maintain endothelial function in the brain, suggesting that glial impairment may underlie the development of retinal edema. The purpose of this study was to test the effects of astrocytes on barrier properties in retinal microvascular endothelial cells. METHODS: Bovine retinal microvascular endothelial cells were exposed to conditioned media from rat brain astrocytes. Transendothelial electrical resistance (TER) was determined on 24-mm Transwell (Cambridge, MA) polycarbonate filters with the End-Ohm device (World Precision Instruments, Sarasota, FL). ZO-1 protein content was quantified by microtiter enzyme-linked immunosorbent assay. RESULTS: Astrocyte-conditioned medium (ACM) significantly increased TER (P < 0.0001) and ZO-1 content (P < 0.01). Both serum-containing and serum- free N1B defined ACM increased ZO-1 expression, but heating abolished the effect. Serum-free ACM decreased cell proliferation by 16%. CONCLUSIONS: Astrocytes release soluble, heat-labile factors that increase barrier properties and tight junction protein content. These results suggest that astrocytes enhance blood-retinal barrier properties, at least in part by increasing tight junction protein expression. Our findings suggest that glial malfunction plays an important role in the pathogenesis of vasogenic retinal edema.

This article has been cited by other articles:

				D. A. Antonetti, A. J. Barber, S. K. Bronson, W. M. Freeman, T. W. Gardner, L. S. Jefferson, M. Kester, S. R. Kimball, J. K. Krady, K. F. LaNoue, et al. Diabetic Retinopathy: Seeing Beyond Glucose-Induced Microvascular Disease Diabetes, September 1, 2006; 55(9): 2401 - 2411. [Abstract] [Full Text] [PDF]

				J. D. Pearson Tightening the Barrier: Mechanical Forces and the Control of Endothelial Permeability Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 10 - 11. [Full Text] [PDF]

				R. C. Geiger, C. M. Waters, D. W. Kamp, and M. R. Glucksberg KGF Prevents Oxygen-Mediated Damage in ARPE-19 Cells Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3435 - 3442. [Abstract] [Full Text] [PDF]

				X. Gu, J. Zhang, D. W. Brann, and F.-S. X. Yu Brain and Retinal Vascular Endothelial Cells with Extended Life Span Established by Ectopic Expression of Telomerase Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 3219 - 3225. [Abstract] [Full Text] [PDF]

				A. J. Barber, D. A. Antonetti, and T. W. Gardner Altered Expression of Retinal Occludin and Glial Fibrillary Acidic Protein in Experimental Diabetes Invest. Ophthalmol. Vis. Sci., October 1, 2000; 41(11): 3561 - 3568. [Abstract] [Full Text]

				K. A. Harkness, P. Adamson, J. D. Sussman, G. A. B. Davies-Jones, J. Greenwood, and M. N. Woodroofe Dexamethasone regulation of matrix metalloproteinase expression in CNS vascular endothelium Brain, April 1, 2000; 123(4): 698 - 709. [Abstract] [Full Text] [PDF]