Investigative Ophthalmology & Visual Science, Vol 38, 635-642, Copyright © 1997 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Effect of high glucose on permeability of retinal capillary endothelium in vitro

MC Gillies, T Su, J Stayt, JM Simpson, D Naidoo and C Salonikas
Department of Ophtalmology, Sydney University, Australia.

PURPOSE: To study the effect of high glucose on the permeability of bovine retinal capillary endothelial cell (BRCEC) monolayers. METHODS: The paracellular permeability of second-passage BRCEC cultured on millipore filters in two chamber transwell inserts was assayed by measuring the peak trans-monolayer electrical resistance and percent equilibration of 14C-inulin 48 hours after it had been added to the luminal chamber. RESULTS: High glucose increased the paracellular permeability of BRCEC monolayers independently of its hypertonic action (5 mM glucose: 154.2 +/- 21.2 and 19.5 +/- 2.4; 30 mM glucose: 134.2 +/- 5.1 [P = 0.01] and 23.5 +/- 2.1 [P = 0.01]; 5 mM glucose + 25 mM mannitol: 168.7 +/- 13.7 ohm.cm2 [P = 0.04] and 19.3% +/- 1.2% 48-hour equilibration of inulin [P = 0.008]). In a separate series of experiments, the authors were unable to show that either aminoguanidine or ponalrestat prevented the effect of high glucose on permeability (30 mM glucose 95.1 +/- 16.7 and 45.4 +/- 5.6; 5 mM glucose: 122.9 +/- 14.2 [P = 0.02] and 36.6 +/- 5.6 [P = 0.001]; 30 mM glucose + aminoguanidine 87.9 +/- 17.5 [P = 0.04] and 75.3 +/- 14.9 [P = 0.6]; 30 mM glucose + ponalrestat 79.9 +/- 12.7 ohm.cm2 [P = 0.1] and 48.2 +/- 2.5% 48-hour equilibration of inulin [P = 0.15]). Ponalrestat did not abrogate the effect of high glucose despite its ability to reduce a high glucose- induced increase in BRCEC intracellular sorbitol levels. CONCLUSIONS: The data are consistent with a role for increased paracellular permeability in breakdown of the blood-retinal barrier in diabetic retinopathy, which appears to be independent of both nonenzymatic glycosylation and the polyol pathway.

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