Beneficial effect of an ACTH4-9 analogue on experimentally induced diabetic autonomic neuropathy in the eye of the rat under general anaesthesia.

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 ACTH4-9 analogue, prevents the occurrence of this sympathetic neuropathy, as the pupil diameters in the ACTH4-9 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.