Differences in vulnerability to desiccating stress between corneal and conjunctival epithelium in rabbit models of short-term ocular surface exposure

Abstract

We evaluate the difference in vulnerability to desiccating stress (DS) between the corneal and conjunctival epithelia to understand different ocular surface staining patterns in dry eye patients. We generated a rabbit model of short-term exposure keratopathy. To induce DS in the ocular surface, rabbit right eyelids were opened for 30 min, with blinking once/minute. Corneal staining scores increased from 3-min post-DS exposure, while conjunctival staining increased from 20-min post-DS. At 20 min, the tear MUC5AC level doubled as compared to pre-DS (p = 0.007). In Western blot analysis, conjunctival AQP5, MUC5AC, and CFTR expression increased significantly in response to DS, compared to control (p = 0.039, 0.002, 0.039, respectively). Immunohistochemistry for CD31 and LYVE-1 were performed. CD31-positive cells and lymphatic space surrounded by LYVE-1-positive cells increased significantly in conjunctival tissue post-DS, compared to control (p = 0.0006, p < 0.0001, respectively). Surface damage was worse in the corneal than in the conjunctival epithelium after DS, by scanning electron microscopy. This study showed that the cornea and conjunctival epithelium show differences in vulnerability to DS. Increased blood vessels and dilated lymphatics, accompanied by increased conjunctival epithelial AQP5, MUC5AC, and CFTR expression, underlie the protective mechanism of the conjunctiva to desiccating stress.