Abstract
Purpose :
Purpose: Diabetic neuropathy is a devastating complication of diabetes with no effective treatment. The etiology of diabetic neuropathy is multifactorial and any effective treatment will likely require some form of combination therapy. In this pre-clinical study we sought to determine the efficacy of monotherapy vs. the combination of menhaden oil, α-lipoic acid, and enalapril on cornea sensation and morphometry as well as vascular and neural endpoints in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes.
Methods :
Methods: Male Sprague-Dawley rats at 12 weeks of age were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin to create a model of type 2 diabetes. Sixteen weeks after the onset of hyperglycemia 12 week treatments consisting of menhaden oil, α-lipoic acid, enalapril or their combination were initiated. Prior to and immediately after treatments we performed analyses of cornea sensitivity to a hyperosmotic solution, corneal nerve morphometry, glucose utilization, vascular reactivity of epineurial arterioles (vessels that provide blood flow to the sciatic nerve), nerve conduction velocity, intraepidermal nerve fiber density and thermal nociception.
Results :
Results: Prior to treatment diabetic rats had decreases in cornea sub-epithelial nerves and corneal sensitivity, impaired glucose utilization and reduced motor and sensory nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density, and impaired vascular relaxation to acetylcholine in epineurial arterioles of the sciatic nerve. Vascular relaxation, nerve conduction velocity and thermal nociception trended to worsen during the treatment phase in untreated diabetic rats. Treating diabetic rats with the combination therapy was more efficacious than monotherapy and improved/reversed all nerve and vascular deficits.
Conclusions :
Conclusions: These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.