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Fushin X. Yu, Feng Wang, Nan Gao; Reduced Innervation And Delayed Re-innervation Post Epithelial Wounding In Type 2 Diabetic Gk Rats. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3562.
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Patients with diabetes are at an increased risk for developing corneal complications and potential vision loss. To understanding the cause of diabetic keratopathy, we investigated innervation and its correlation with delayed corneal epithelial wound healing in type 2 diabetic Goto-Kakizaki (GK) rats.
The blood sugar levels of GK and the age-matched Wister rats were measured weekly, starting at month 2. Corneal sensitivity was measured with an esthesiometer (Cochet-Bonnet) in unanesthetized rats. Ocular surface irregularity was examined with a lit Lamp for fluorescein and Rose Bengal staining. Cornea fragility was determined by applying dry 4-mm round PVC membrane for 30 seconds, followed by fluorescein slit Lamp microscopy. Wound healing was determined using an in vivo corneal epithelial debridement model. The sensory nerve fibers and ends were examined with in vitro confocal Microscopy (Confoscan-4) and whole mount immunostaining of beta III-tubulin.
GK rats are smaller than the aged controlled Wistar rats from which the GK rats were derived. The blood sugar levels of GK rats at month 2 are significantly higher than that of Wister rats. At four months, the male GK rats have average blood sugar levels >200 mg/dL while the control rats have <100 mg/dL. GK rats were Rose Bengal positive and had increased cornea fragility. Fewer nerve fibers were detected by Confoscan in GK, compared to Wister rats. While nerve fiber densities were similar near limbal region, in central cornea, thinner, less abundant sub-basal nerve plexuses with fewer branches in GK rat corneas. Corneal epithelial wound closure was delayed and re-innervation was slow and incomplete in GK rats.
Diabetic neuropathy occurs in the cornea of type-2 diabetic GK rats and defects in sensory nerve may contribute to delayed epithelial wound healing in diabetic corneas.
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