involucrin and Conjunctival-Diseases

To investigate the molecular mechanism of pathological keratinization in severe ocular surface diseases based on the process of epidermal physiological keratinization and the gene expression profile of ocular surface epithelium.. We examined conjunctiva covering corneas which had ocular surface diseases in which pathological keratinization was seen. We then investigated the expression of epidermal keratinization-related proteins and clusterin, which is the most abundant gene transcript in human corneal epithelium.. Semiquantitative reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry showed that transglutaminase 1, involucrin, filaggrin, and cytokeratin 1/10 expression was upregulated in keratinized conjunctiva compared to normal conjunctiva. On the other hand, the level of clusterin expression in the diseased ocular surfaces was significantly lower than normal. We also concluded that clusterin expression may depend on the severity of the pathological keratinization.. Various keratinization-related proteins and clusterin are most likely to be involved in the pathogenesis of cicatrizing ocular surface diseases.

Topics: Clusterin; Conjunctiva; Conjunctival Diseases; Filaggrin Proteins; Glycoproteins; Humans; Intermediate Filament Proteins; Keratinocytes; Keratins; Molecular Chaperones; Protein Precursors; Transglutaminases

Topics: Conjunctiva; Conjunctival Diseases; Humans; Immunohistochemistry; Keratins; Membrane Proteins; Metaplasia; Mucous Membrane; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transglutaminases

In severe ocular surface diseases, pathologic keratinization of the ordinarily nonkeratinized corneal and conjunctival mucosal epithelia results in severe visual loss. The expression in conjunctivalized corneas of various proteins known to play important roles in the physiological keratinization process in human epidermis was examined to better understand the mechanism of keratinization.. Conjunctiva covering the cornea was examined in 12 eyes with ocular surface disease in the chronic cicatricial phase. These comprised four Stevens-Johnson syndrome, four ocular cicatricial pemphigoid, and four chemical injuries. Normal conjunctivas from four age-matched individuals served as controls. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to investigate transglutaminase 1 gene expression and immunohistochemistry to study the expression of transglutaminase 1 protein along with other keratinization-related proteins (involucrin, loricrin, filaggrin, and cytokeratins 1 and 10) and cytokeratin pairs 4/13 and 3/12.. Semiquantitative RT-PCR showed that transglutaminase 1 mRNA expression was upregulated in keratinized conjunctiva compared with normal. Also, in this tissue, immunohistochemistry demonstrated elevated levels of transglutaminase 1, involucrin, filaggrin, and the cytokeratin pair 1/10. Levels of loricrin and cytokeratin pairs 4/13 and 3/12, however, remained the same.. Various keratinization-related proteins, transglutaminase 1 included, are most likely involved in the pathogenesis of cicatrizing ocular surface diseases.

Topics: Adult; Aged; Aged, 80 and over; Conjunctiva; Conjunctival Diseases; Female; Filaggrin Proteins; Fluorescent Antibody Technique, Indirect; Humans; Intermediate Filament Proteins; Keratins; Male; Membrane Proteins; Middle Aged; Pemphigoid, Benign Mucous Membrane; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stevens-Johnson Syndrome; Transglutaminases; Up-Regulation

Keratinization of the ocular surface epithelium is associated with various disorders impairing vision. We immunohistochemically determined whether the ocular surface epithelia express involucrin, and whether its expression pattern may differ in benign vs. malignant disorders. Expression of cytokeratins was also examined to provide further information relative to the epithelial differentiation.. We evaluated 17 specimens; 6 specimens of the normal ocular surface epithelia, 3 specimens from cases of conjunctival intraepithelial neoplasia (CIN), 6 of conjunctival squamous cell carcinoma (SCC) and 2 of conjunctivae from cases of superior limbic keratoconjunctivitis (SLK).. Corneal epithelium exhibited intracellular immunoreactivity for involucrin. Four of the 6 specimens of bulbar conjunctival epithelium showed involucrin immunoreactivity in the perimembranous region, whereas the fornical conjunctiva was negative. Cornified envelope in SLK specimens was positive for involucrin. The CIN showed its immunoreactivity in the perimembranous region in all levels of the hyperproliferative epithelium without keratinization, i.e., similar to the bulbar conjunctiva. The neoplastic cells of well-differentiated SCC showed involucrin in the perimembranous region, and those of moderately- to poorly-differentiated SCC have involucrin in their cytoplasm. The expression pattern of cytokeratins was unrelated to grade of malignancy in ocular SCC.. The epithelia of normal subjects and of CIN expresses involucrin without keratinization. In contrary, the keratinized SLK epithelium markedly expresses involucrin in the cornified envelope. The subcellular immunolocalization of involucrin in the ocular SCC may help in evaluating the differentiation, i.e., malignancy, of neoplastic cells.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Conjunctiva; Conjunctival Diseases; Conjunctival Neoplasms; Epithelium; Eye Proteins; Female; Filaggrin Proteins; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Keratoconjunctivitis; Male; Middle Aged; Protein Precursors