Corneal innervation as a window to peripheral neuropathies

Abstract

The cornea receives the densest sensory innervation of the body, which is exclusively from small-fiber nociceptive (pain-sensing) neurons. These are similar to those in the skin of the legs, the standard location for neurodiagnostic skin biopsies used to diagnose small-fiber peripheral polyneuropathies. Many cancer chemotherapy agents cause dose-related, therapy-limiting, sensory-predominant polyneuropathy. Because corneal innervation can be detected non-invasively, it is a potential surrogate biomarker for skin biopsy measurements. Therefore, we compared hindpaw-skin and cornea innervation in mice treated with neurotoxic chemotherapy. Paclitaxel (0, 5, 10, or 20 mg/kg) was administered to C57/Bl6 mice and peri-mortem cornea and skin biopsies were immunolabeled to reveal and permit quantitation of innervation. Both tissues demonstrated dose-dependent, highly correlated (r = 0.66) nerve fiber damage. These findings suggest that the quantification of corneal nerves may provide a useful surrogate marker for skin peripheral innervation.