Fig. 6: Unilateral corneal topical treatment with capsaicin induces corneal neuropathy in the contralateral eye.

a Unilateral corneal topical treatment with capsaicin (Cap) was performed in WT mice by applying a 2-mm filter paper disk soaked in 0.5 mg/ml Cap or vehicle (Ct) onto the right cornea for 5 min under anesthesia (days 0 and 2). b Representative micrographs (day 4) of external eye appearance (left) and corneal epithelial dye uptake (right). c Representative micrographs of Ct and Cap-treated right corneas with anti-tubulin β3 (nerve-specific) staining. d–f The corneal mechanosensitivity thresholds (d), ocular Cap sensitivity (e) and eye-closing ratio (f) as measured separately on the right and left sides of Ct and Cap-treated mice. g–i The density of intraepithelial corneal innervation in anti-tubulin β3 staining of corneal wholemounts from the right and left eyes of Ct and Cap-treated mice assessed at three different levels: subapical (g) (percent area occupied by nerve endings) and midepithelial (h) (count of nerve endings per field) nerve ending density and complexity of subbasal nerves (i) (sum of intersections at all Sholl radii). All experiments were performed twice or more with six mice per group per experiment. To compare means, two-way ANOVA was used with Dunnett’s post hoc test. *P < 0.05, ***P < 0.001, ****P < 0.0001. ns, not significant.