title: 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.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 20 Staniford St., Boston, MA 02114, USA. giulio.ferrari@schepens.harvard.edu
authors.forename: Giulio
authors.initials: G
authors.lastname: Ferrari
authors.forename: Nambi
authors.initials: N
authors.lastname: Nallasamy
authors.forename: Heather
authors.initials: H
authors.lastname: Downs
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
authors.forename: Anne Louise
authors.initials: AL
authors.lastname: Oaklander
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D001706:Biopsy; D003315:Cornea / Q000294:innervation* / Q000473:pathology; D003389:Cranial Nerve Diseases / Q000139:chemically induced / Q000175:diagnosis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009882:Ophthalmic Nerve / Q000187:drug effects / Q000473:pathology*; D017239:Paclitaxel / Q000633:toxicity; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000175:diagnosis*; D012867:Skin / Q000294:innervation* / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel
keywords: CCM; CIPN; CNFD; IENFD; chemotherapy-induced peripheral neuropathy; corneal nerve-fiber density; corneal nerves; intraepidermal nerve-fiber density; in vivo corneal confocal microscopy; peripheral neuropathy