Changes in conjunctival clusterin expression in severe ocular surface disease

Abstract

Purpose: Clusterin is a unique gene transcript in the human ocular surface epithelia and is synthesized by and localized in mucosal epithelia in general. It is not present, however, in keratinized epithelia, such as epidermis. In severe ocular surface disease, pathologic keratinization (squamous metaplasia) of the ordinarily nonkeratinized corneal and conjunctival mucosal epithelia results in severe visual loss. In the current study, the expression of clusterin was examined in conjunctivalized corneas with severe ocular surface disease.

Methods: We examined conjunctiva covering cornea in eight eyes with ocular surface disease (Stevens-Johnson syndrome and ocular cicatricial pemphigoid) in which pathologic keratinization was present. Normal conjunctiva from four age-matched individuals served as the control. Semiquantitative RT-PCR was used to investigate expression of the clusterin gene. Immunohistochemistry was used to study the distribution of clusterin protein.

Results: The level of clusterin mRNA was significantly lower than normal in the diseased ocular surfaces. Clusterin protein was also markedly decreased in keratinized conjunctiva compared with that in normal eyes.

Conclusions: Clusterin expression is markedly reduced in the pathologic, keratinized ocular surface epithelium, suggesting its importance in maintaining the ocular surface epithelium as a nonkeratinizing epithelium.