Repeated monitoring of corneal nerves by confocal microscopy as an index of
peripheral neuropathy in type-1 diabetic rodents and the effects of topical
Authors Chen DK, Frizzi KE, Guernsey LS, Ladt K, Mizisin AP, Calcutt NA
Submitted By Nigel Calcutt on 4/15/2014
Status Published
Journal Journal of the peripheral nervous system : JPNS
Year 2013
Date Published 12/1/2013
Volume : Pages 18 : 306 - 315
PubMed Reference 24147903
Abstract We developed a reliable imaging and quantitative analysis method for in vivo
corneal confocal microscopy (CCM) in rodents and used it to determine whether
models of type 1 diabetes replicate the depletion of corneal nerves reported in
diabetic patients. Quantification was reproducible between observers and stable
across repeated time points in two rat strains. Longitudinal studies were
performed in normal and streptozotocin (STZ)-diabetic rats, with innervation of
plantar paw skin quantified using standard histological methods after 40?weeks
of diabetes. Diabetic rats showed an initial increase, then a gradual reduction
in occupancy of nerves in the sub-basal plexus so that values were significantly
lower at week 40 (68?±?6%) than age-matched controls (80?±?2%). No significant
loss of stromal or intra-epidermal nerves was detected. In a separate study,
insulin was applied daily to the eye of control and STZ-diabetic mice and this
treatment prevented depletion of nerves of the sub-basal plexus. Longitudinal
studies are viable in rodents using CCM and depletion of distal corneal nerves
precedes detectable loss of epidermal nerves in the foot, suggesting that
diabetic neuropathy is not length dependent. Loss of insulin-derived
neurotrophic support may contribute to the pathogenesis of corneal nerve
depletion in type 1 diabetes.

Investigators with authorship
Nigel CalcuttUniversity of California San Diego