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Publication
Repeated monitoring of corneal nerves by confocal microscopy as an index of
peripheral neuropathy in type-1 diabetic rodents and the effects of topical
insulin.
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
Name
Institution
Nigel Calcutt
University of California San Diego
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Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
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