The Therapeutic Use of Atropine in Diabetic Neuropathy
Authors:Nigel Calcutt, Katie Frizzi, Andre Mota
Mentor:Nigel Calcutt, Professor of Pathology, University of California, San Diego
Diabetic neuropathy, a neurological complication of diabetes, is associated with significant rates of morbidity and mortality. Since limited therapeutic approaches currently exist for diabetic degenerative neuropathy, we investigated the efficacy of novel therapeutic approaches. Specifically, we focused on the use of atropine, an alkaloid and commonly-used drug that affects the autonomic nervous system. To investigate the therapeutic potential of atropine, insulin-dependent (type-1) diabetes was induced in mice via injection of streptozotocin (STZ), producing insulin deficiency and hyperglycaemia within 3 days. Atropine (2% in gel) was applied daily to the eyes or feet of mice. Testing for neuropathy was performed on the 4th and 8th weeks of the study. Severity of neuropathy was determined by assessing paw sensitivity to touch and heat and by measuring nerve conduction velocity. Corneal nerves were also imaged in live animals throughout the study by corneal confocal microscopy (CCM) and captured images will be used to measure the nerve fiber density by stereological techniques (values in % occupancy). At the end of the study we will also measure cutaneous innervation of skin biopsies by counting intra-epidermal nerve fibers immunostained with PGP 9.5 under a light microscope (values in #/mm of dermal:epidermal junction). Our initial results suggest that atropine may prevent onset of behavioral and electrophysiological indices of neuropathy in diabetic mice, supporting use of this drug as a possible therapeutic approach to the treatment of diabetic neuropathy.