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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Various keratinization-related proteins, transglutaminase 1 included, are most likely involved in the pathogenesis of cicatrizing ocular surface diseases.
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan.
T
T
Nakamura
K
K
Nishida
A
A
Dota
M
M
Matsuki
K
K
Yamanishi
S
S
Kinoshita
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003228:Conjunctiva / Q000378:metabolism* / Q000473:pathology; D003229:Conjunctival Diseases / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000091344:Filaggrin Proteins; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis*; D007633:Keratins / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D010390:Pemphigoid, Benign Mucous Membrane / Q000378:metabolism / Q000473:pathology; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013262:Stevens-Johnson Syndrome / Q000378:metabolism / Q000473:pathology; D011503:Transglutaminases / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; C064554:loricrin; C032253:involucrin; D007633:Keratins; D011503:Transglutaminases; C105804:transglutaminase 1