Title

Myogenic Tone in Bovine Retinal Arteries: Effect of Acute High Glucose

Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Mary P. Owen, PhD JD

Second Advisor

Brian M. Matayoshi, PhD

Third Advisor

Richard E. White, PhD

Fourth Advisor

Shu Zhu, PhD

Fifth Advisor

Bonnie A. Buxton, PhD

Abstract

A reduction in retinal blood flow is one of the early features of diabetic retinopathy. Hyperglycemia is an important risk factor for vascular complications in diabetes and is believed to modulate protein kinase C (PKC) activation in the retina. The object of this study was to evaluate the effect of acute exposure to high glucose (25.5 mM) on myogenic tone in the retinal circulation and to determine whether that myogenic tone can be modified by inhibition of PKC. Branches of the retinal artery were removed from the bovine retinal sheath and pressurized using an arteriograph system. At 60, 80 and 100 mm Hg, significantly more tone (4.2 ± 1 A%, 3.5 ± 0.8% and 3.7 ± 1.1 %, respectively) developed in high glucose buffer (25.5 mM) than in normal glucose buffer (5.5 mM). Chelerythrine, a nonselective PKC inhibitor, blocked the effect of high glucose on myogenic tone and reduced the level of myogenic tone in normal glucose. In addition, western blot results showed that isoforms alpha, beta, delta, epsilon, iota and lambda of PKC are expressed in bovine retinal arterial vascular tissue. To our knowledge, this is the first study to show that high glucose concentration increases myogenic tone in isolated retinal arteries through a PKC mechanism. Further studies related to the determination of a possible PKC isoform specificity for this effect have potential for the development of strategies for delaying, stopping or even reversing diabetic retinopathy. In addition, exploration of an ion channel specificity for this effect could also be of substantial relevance in the development of strategies to intervene in diabetic retinopathy, (Supported by eeDA and HL-68026)

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