Sensory nerve regeneration after epithelium wounding in normal and diabetic corneas

Abstract

The cornea is the most densely innervated mammalian tissue. The sensory nerves are responsible for sensations of dryness, temperature, touch and pain, and play important roles in blink reflex, wound healing and tear production. Many ocular and systemic diseases can adversely affect corneal sensory nerve and, consequently, impair its function. One such systemic disease is diabetes mellitus which causes sensory degeneration, diabetic neurotrophic keratopathy and delayed wound healing. In this review, the authors summarize the recent discoveries revealing the mechanisms underlying the pathogenesis of diabetic neurotrophic keratopathy and the impairment of sensory nerve regeneration in post wound diabetic corneas in using animal model of human diabetes. Because it is generally believed that common mechanisms are operative in the pathogenesis of diabetic peripheral neuropathy in different tissues, the findings in the corneas have implications in other tissues such as the skin, which often leads to foot ulceration and amputation in diabetic patients.

Keywords:

• cornea
• diabetes
• diabetic peripheral neuropathy
• sensory nerve
• wound healing

Financial & competing interests disclosure

The research in Dr. Yu's laboratory is partially funded by grants from NIH/NEI (EY010869, EY017960). Kresge Eye Institute received Unrestricted Grant from Research to Prevent Blindness. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Diabetes mellitus is a rapidly growing major health problem in the US and worldwide.

• Seventy percent of diabetic patients have complications in the cornea that are clinically termed as diabetic keratopathy.

• One of the underlying causes of diabetic keratopathy is the loss of neurotrophic support, resulting from degeneration of sensory nerves, and is termed as diabetic neurotrophic keratopathy (DNK).

• The cornea is mostly a heavily innerved tissue in our body. Degeneration of corneal sensory nerve can be detected in the early stage of diabetes.

• Corneal nerve damage is directly related to the severity of somatic neuropathy in diabetic patients, that is, DNK is a component of diabetic peripheral neuropathy (DPN).

• DPN is the underlying cause of chronic foot ulcers; which can lead to limb amputation.

• Currently, the only method of directly examine peripheral nerves is to conduct skin punch or sural/peroneal nerve biopsies, which are uncomfortable and invasive.

• A battery of non-invasive techniques, including corneal confocal microscopy and non-contact corneal esthesiometry, and tear measurement have been developed and routinely used clinically for assessing DNK.

• Assessing this damage non-invasively in the cornea has been proposed as an effective method for the early detection, diagnosis, staging the severity and monitoring the progression of DPN.

Notes