Beneficial effect of an ACTH 4–9 analogue on experimentally induced diabetic autonomic neuropathy in the eye of the rat under general anaesthesia

Abstract

While peripheral polyneuropathy is a well-known complication in diabetes mellitus, and the subject of a great deal of study, the clinical importance of autonomic diabetic neuropathy is increasingly recognised. Using an animal model, where the pupil diameter of the eye serves as a parameter of autonomic function, we produced an age and weight curve of pupil diameter and studied the development of autonomic neuropathy in rats with streptozotocin-induced diabetes. We show that diabetic rats develop significantly ( P < 0.009) smaller pupils compared with controls, most probably due to a defective sympathetic input, caused by sympathetic neuropathy. Treatment with the neurotrophic peptide Org 2766, a synthetic ACTH 4–9, analogue, prevents the occurrence of this sympathetic neuropathy, as the pupil diameters in the ACTH 4–9, analogue-treated group are significantly ( P < 0.05) larger than the pupils of placebo-treated rats, and are comparable to the pupil diameters of the rats in the control group.