Short–Term Instillation of Latanoprost Does Not Affect Occludin Expression in Experimental Diabetic Rat Retina

Abstract

Abstract: : Purpose: Last year we showed that latanoprost eye drops reduced apoptosis of inner retinal neurons of streptozotocin (STZ)–induced diabetic rat retina and increased phosphorylation of pro–survival p44/p42 mitogen–activated protein kinase in retinal homogenates (ARVO 2004, 851). However, latanoprost may exacerbate microangiopathy. The purpose of this study is to test whether latanoprost eye drops have favorable or deleterious effects on expression of occludin, one of the major tight junction proteins in retinal vessels. Methods: Three–month STZ–diabetic rats or age matched controls received 10 µl balanced–salt–solution (BSS) in the left eye and latanoprost in the right for 5 days. In one group, retinas were dissected, flat mounted, and subjected to terminal dUTP nick end labeling (TUNEL) staining or occludin immunofluorescence. In the other, retinal homogenates were electrophoresed and probed for occludin. TUNEL positive cells per unit retinal area and occludin contents were compared. Results: The mean glucose levels were 522 ± 30.3 and 86.7 ± 17.0 mg/dl in diabetic and normal groups (P<0.01 unpaired t–test), respectively. TUNEL positive cells were 23.6 ± 9.0 /0.5cm² in diabetic retinas with BSS instillation and 10.0 ± 3.0 /0.5cm² in those with latanoprost instillation (P<0.01 ANOVA with Bonfferoni crrection), whereas there was few TUNEL positive cells in control retinas. Occludin immunoreactivity in the capillary was reduced in diabetic retinas as compared with controls, which was not affected by latanoprost instillation. Total occludin contents were reduced to less that 49.3% of controls (P<0.01) both in diabetic retinas with BSS instillation and those with latanoprost instillation. There was no significant difference between retinas with BSS and those with latanaprost instillation. Conclusions: Short–term instillation of latanoprost did not affect occludin expression in diabetic retina with exerting the neuroprotective effect.

Keywords: diabetic retinopathy • apoptosis/cell death • drug toxicity/drug effects