Effect of glycemic control on corneal nerves and peripheral neuropathy in streptozotocin-induced diabetic C57Bl/6J mice.
We sought to determine the impact that duration of hyperglycemia and control has on corneal nerve fiber density in relation to standard diabetic neuropathy endpoints. Control and streptozotocin-diabetic C57Bl/6J mice were analyzed after 4, 8, 12, and 20 weeks. For the 20-week time point, five groups of mice were compared: control, untreated diabetic, and diabetic treated with insulin designated as having either poor glycemic control, good glycemic control, or poor glycemic control switched to good glycemic control. Hyperglycemia was regulated by use of insulin-releasing pellets. Loss of corneal nerves in the sub-epithelial nerve plexus or corneal epithelium progressed slowly in diabetic mice requiring 20 weeks to reach statistical significance. In comparison, slowing of motor and sensory nerve conduction velocity developed rapidly with significant difference compared with control mice observed after 4 and 8 weeks of hyperglycemia, respectively. In diabetic mice with good glycemic control, average blood glucose levels over the 20-week experimental period were lowered from 589 ± 2 to 251 ± 9 mg/dl. All diabetic neuropathy endpoints examined were improved in diabetic mice with good glycemic control compared with untreated diabetic mice. However, good control of blood glucose was not totally sufficient in preventing diabetic neuropathy.
Department of Veterans Affairs, Iowa City Health Care System, Iowa City, IA, USA; Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, USA.
Matthew S
MS
Yorek
Alexander
A
Obrosov
Hanna
H
Shevalye
Sergey
S
Lupachyk
Matthew M
MM
Harper
Randy H
RH
Kardon
Mark A
MA
Yorek
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D003315:Cornea / Q000294:innervation*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000209:etiology / Q000503:physiopathology*; D019573:Epithelium, Corneal / Q000294:innervation; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000502:physiology*; D013311:Streptozocin / Q000633:toxicity
D000900:Anti-Bacterial Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin
corneal confocal microscopy; corneal nerves; diabetic peripheral neuropathy; nitrotyrosine