Clinical Observations and Histopathological Findings of Mitomycin C Topically Treated Cynomolgus Monkey Corneas

Abstract

Purpose: : To describe the clinical observations and histopathological changes following topical 0.2 % Mitomycin C (MMC) treatment in the cynomolgus monkey cornea.

Methods: : The central cornea of 10 anesthetized Cynomolgus monkeys received a single topical dose for 2 min as follows: Group 1 (n=5), bilateral 0.9% saline, right cornea debrided with contralateral eye as nondebrided control; Group 2 (washed with BSS after dosing, n=5) bilateral 0.2% MMC, right cornea debrided with contralateral eye as control. Hand-held slit lamp biomicroscopy and indirect ophthalmoscopy were carried out at baseline and on Day 14 following dosing. Animals were euthanized on Day 15 and central corneas were removed and processed for hematoxylin and Eosin (H&E) and periodic acid schiff’s (PAS) staining.

Results: : Ophthalmic exams of Group 1 on Day 14 showed re-epithelialization (Group 2 also) and slight corneal haze and subtle corneal epithelial pigmentation in 4/5 debrided eyes dosed with 0.9% saline with no findings in control eyes. In contrast, 4/5 debrided eyes dosed with 0.2% MMC (Group 2) showed subtle corneal edema with all 5 having diffuse pigmentation of the anterior cornea. The contralateral, nondebrided MMC control eyes lacked these findings. Histopathology showed a lack of abnormal findings in nondebrided/saline and debrided/saline controls. In Group 2, the nondebrided/ MMC control corneas showed flattened epi and endothelium in 3/5 corneas similar to debrided/MMC treated eyes. However, the epi changes in the nondebrided/MMC treated eyes were less severe compared to those of the debrided/MMC treated eyes. In addition, in the debrided/MMC corneas, pigment in basal and intermediate epi, inflammatory cells at the periphery of the cornea and decreased endothelial nuclei were noted in all 5 corneas. PAS staining confirmed the peripheral location of the pigment in the epi and showed intact basement membranes of similar thickness.

Conclusions: : Clinical observations were confirmed by histopathology, which also revealed the presence of inflammatory cells in these corneas. In addition, histopathology noted some degree of epi and endothelial defects in nondebried/MMC treated corneas. While clinical observations cautioned the possible defects induced by exposure to MMC with a compromised epithelium, histopathology demonstrated a possible deleterious effect of exposure to MMC without a compromised epithelium.

Keywords: cornea: clinical science • cornea: basic science • microscopy: light/fluorescence/immunohistochemistry