Elevated expression of transglutaminase 1 and keratinization-related proteins in conjunctiva in severe ocular surface disease

PURPOSE. In severe ocular surface diseases, pathologic keratinization of th e ordinarily nonkeratinized corneal and conjunctival mucosal epithelia resu lts in severe visual loss. The expression in conjunctivalized corneas of va rious proteins known to play important roles in the physiological keratiniz ation process in human epidermis was examined to better understand the mech anism of keratinization. METHODS. Conjunctiva covering the cornea was examined in 12 eyes with ocula r surface disease in the chronic cicatricial phase. These comprised four St evens-Johnson syndrome, four ocular cicatricial pemphigoid, and four chemic al injuries. Normal conjunctivas from four age-matched individuals served a s controls. Semiquantitative reverse transcription-polymerase chain reactio n (RT-PCR) was used to investigate transglutaminase 1 gene expression and i mmunohistochemistry to study the expression of transglutaminase 1 protein a long with other keratinization-related proteins (involucrin, loricrin, fila ggrin, and cytokeratins 1 and 10) and cytokeratin pairs 4/13 and 3/12. RESULTS. Semiquantitative RT-PCR showed that transglutaminase 1 mRNA expres sion was upregulated in keratinized conjunctiva compared with normal. Also, in this tissue, immunohistochemistry demonstrated elevated levels of trans glutaminase 1, involucrin, filaggrin, and the cytokeratin pair 1/10. Levels of loricrin and cytokeratin pairs 4/13 and 3/12, however, remained the sam e. CONCLUSIONS. Various keratinization-related proteins, transglutaminase 1 in cluded, are most likely involved in the pathogenesis of cicatrizing ocular surface diseases.