Detecting diabetic neuropathy in rodents by imaging corneal nerves
Nigel Calcutt   (La Jolla, CA)
Visualization of corneal nerves by confocal microscopy is currently being developed as a sensitive and completely non-invasive method of detecting neuropathy in diabetic patients that allows the repeated measurements necessary for longitudinal studies of drug efficacy. Corneal confocal microscopy (CCM) has been applied to live rodents and other species and our exploratory studies indicate that corneal nerves can also be visualized ex vivo. In the proposal we will establish optimal conditions for visualizing and quantifying corneal nerves in rats and mice in vivo and in eyes from rats ex vivo. Once these conditions are established, we will use CCM to detect neuropathy in eyes of control and diabetic mice provided from new models of diabetes developed by the AMDCC. We will also compare the structural neuropathy detected by CCM with the current methods of phenotyping neuropathy in tissues from these animals which are reduced axonal calibre in the sciatic nerve and loss of intraepidermal nerve fibers in the paw skin. The sensitivity of CCM to detect onset and progression of neuropathy in a longitudinal study of the eyes of mouse models of type 1 and type 2 diabetes will also be studied and compared with onset and progression of nerve conduction velocity slowing and paw thermal hypoalgesia. The purpose of these studies is to establish the viability of CCM as a sensitive means of detecting neuropathy in diabetic rodents so that it can be used to phenotype new models of diabetes being developed by the AMDCC and to allow assessment of the efficacy of new therapeutics in rodent models prior to clinical trials using the same end point and equipment.