Type1 Transglutaminase and the Differentiation of Corneal Epithelium

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The corneal epithelium continueously proliferates and properly differentiates in order to maintain its transparency. To clarify the process of corneal epithelial differentiation, we attempted to analyze the expression of the transglutaminase (TG), one of the enzymes which regulate keratinization, in the human corneal and conjunctival epithelium. The expression of mRNA for the TG was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR). Subsequent immunohistochemical study has revealed the presence of the cornifin, a substrate for the TG,in the corneal and conjunctival epithelium as well.In the next study, we monitored the chronological change of the TG in the corneal epithelium of the rats which were fad with vitamin A-deficient diet. Superficial punctate keratopathy appeared together with decreased lacrimation at 9 weeks after initiating the regimen, progressing to filamentary keratitis by week 12. Finally, the lesion simulating keratomalacia developed at Week 18.The seniquatative RT-PCR has demonstrated that the expression of type 1 TG was increased well in accordance with the duration of the treatment, while that of type 2 TG was gradually decreased.In another study, we obtained hyperimmune sera from the rabbit which had been immunized with the recombinant TG protain. Immunohistochemical studies using this particular antibody has demonstrated the presence of TG in the corneal amd conjunctival epithelium of the rats and humans. The staining was found to be intense especially at the cell membrane.These result strongly indicated that TG is involved in the keratinization process of corneal and conjunctival epithelium, shedding an insight to search for a new substance which is able to control the differentiation of ocular surface eipthelia.