Hyperglycemia Suppresses Age-Related Increases in Corneal Peripheral Sensory Nerves in Wistar Bon Kobori (WBN/Kob) Rats.

Purpose: Nerve fiber density in the cornea is an alternative marker for diabetic peripheral neuropathy combined with intraepidermal nerve fiber density (IENFD). Recent studies investigated corneal nerves using rodent models of diabetes. Male Wistar Bon Kobori (WBN/Kob) rats spontaneously develop long-lasting diabetes and human-like diabetic peripheral neuropathy with vascular lesions. This study investigated corneal nerve fiber density and IENFD in diabetic male WBN/Kob rats as morphological markers of diabetic peripheral neuropathy.

Methods: Male WBN/Kob rats exhibit abnormal glucose tolerance and diabetes at approximately 30 weeks of age, which progresses until approximately 90 weeks of age. Male WBN/Kob rats aged 36 and 90 weeks were therefore used for histological investigations and compared with age-matched nondiabetic female rats.

Results: Terminal epithelial nerve density and subbasal nerve plexus density in the central cornea were significantly greater in nondiabetic female rats aged 90 weeks when compared with nondiabetic female rats aged 36 weeks. However, terminal epithelial nerve density and subbasal nerve plexus density did not increase with age in diabetic male WBN/Kob rats, instead lowering by up to 40%, relative to measurements in nondiabetic female rats aged 90 weeks. However, this difference was not statistically significant. IENFD was significantly lower in diabetic male rats aged 90 weeks than in male rats aged 36 weeks, but did not differ between diabetic male rats and nondiabetic female rats aged 90 weeks.

Conclusions: In WBN/Kob rats, hyperglycemia suppresses an age-related increase in peripheral sensory corneal nerve density; therefore, corneal sensory nerves may be important morphological markers of diabetic peripheral sensory neuropathy.