Abstract
Purpose :
Diabetic neuropathy represents the third most prevalent neurological disorder. Recent studies demonstrated that diabetic corneal nerve alternations may be a potential surrogate marker to reveal the peripheral nerve status of diabetic patients. Therefore, it is of great importance to investigate the dynamic changes of corneal nerves and its association with intraepidermal nerve damage upon hyperglycemia, which is helpful for further studies on the underlying pathophysiological mechanisms and therapeutic targets of diabetic neuropathy. We tested whether dynamic loss of corneal nerve occurred in the early stage of diabetic neuropathy using in vivo microscopy in a diabetic mouse model.
Methods :
8-week-old Thy-1/YFP mice were injected with 50 mg/kg streptozotocin (STZ) for 5 consecutive days for hyperglycemia induction. Bodyweight and blood glucose levels were recorded weekly. Corneal sensitivity was tested with Cochet-Bonnet esthesiometer weekly. At 4, 8, 12, 16, 20, and 24 weeks after STZ injection, corneal nerves and epidermal nerves from the hind paw and leg skin were visualized with in vivo microscopy. Meanwhile, corneal and epidermal nerve analyses were performed on corneal flat mount and skin from the hind paw and leg, respectively using Imaris and Neuron J software.
Results :
Hyperglycemia was successfully induced and led to a loss of corneal nerve fiber. At 4 weeks after STZ injection, the total number of nerve fibers in the central cornea showed a significant loss (23.6±3.7%) while subbasal nerve plexus in the central cornea showed a loss in corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL) and corneal nerve branch density (CNBD). At 16 weeks after STZ injection, the total number of nerve fibers in the peripheral cornea was significantly decreased (46.2±4.6%). Subbasal nerve plexus in peripheral cornea showed a loss in CNFD, CNFL, and CNBD. At 24 weeks after STZ injection, corneal nerve fibers could be detected except the ones in the stroma. More importantly, these pathological features occurred earlier than changes in epidermal nerve fibers and earlier than cornea functionality (corneal sensitivity test).
Conclusions :
Our results show that in vivo microscopy, a non-invasive tool for longitudinal nerve fiber detection, revealed dynamic changes in corneal nerves upon hyperglycemia, suggesting that monitoring of corneal nerve fiber may lead to earlier diagnosis of diabetic neuropathy.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.