Abstract
Abstract: :
Purpose: Diabetes–mediated retinal dysfunction is associated with increased permeability and altered blood flow. No studies to date have specifically focused on functional assessment of ophthalmic arteries in diabetic rodent models. In this study functional alterations were assessed in ophthalmic arteries of both BBZ/Wor Type II diabetic rat and normoglycemic rat acutely exposed to high glucose in vitro. Methods: Ophthalmic arteries from obese diabetic BBZ/Wor (DM), their lean control (N), and Sprague–Dawley (SD) rats were dissected, mounted in an arteriograph and pressurized at 70 mmHg for diameter measurements. Pressure–dependent changes in arterial tone and reactivity to carbachol (an analogue of acetylcholine) and phenylephrine were evaluated. Results: Pressure–dependent increase in myogenic tone was attenuated in arteries from DM rats compared to those of N rats (p<0.01) while reactivity to carbachol and phenylephrine were unchanged. In SD ophthalmic arteries, myogenic tone was enhanced (p<0.01) and attenuated (p<0.01) by exposure to 25 and 40 mmol/L glucose, respectively, while unchanged in by 25 and 36 mmol/L mannitol, an osmotic control. Dilation to carbachol was unaffected. Constriction to phenylephrine was decreased by 40 mmol/L (p<0.05). Effects of high glucose on myogenic tone were not observed in the absence of endothelium. Conclusions: These results suggest that pressure–mediated autoregulation of blood flow is attenuated in Type II diabetes that could result in increased permeability of the ophthalmic artery and exposure of retinal arteries to increased blood flow. Effect of in vitro acute exposure to high glucose on myogenic tone is concentration– and endothelium–dependent producing either enhancement or attenuation. Reactivity to the endothelium–dependent dilator, carbachol, was not affected by high glucose but to the vasoconstrictor, phenylephrine, was attenuated by 40 mmol/L glucose. Future studies in ophthalmic artery are focused on identifying endothelial factors/radicals that differentially influence pressure–mediated autoregulation in the gluocse concentration–dependent manner observed here.
Keywords: diabetic retinopathy • blood supply • diabetes