ASSESSMENT OF ANTICOLLAGENASE TREATMENTS AFTER INSERTION OF A KERATOPROSTHETIC MATERIAL IN THE RABBIT CORNEA

Purpose. This study was performed to evaluate the enzyme production in response to implantation of the hydrogel material used in the experim ental Chirila keratoprosthesis (KPro) and to assess the effects of fiv e topical drugs on enzyme production and activity. KPros may be extrud ed from the cornea as a result of tissue melting, a process that invol ves excessive enzyme activity. To reduce the possibility of implant lo ss for the hydrogel Chirila KPro, a number of antiinflammatory drugs t hat have been used to treat other corneal melting conditions were inve stigated for their effect on initial collagenase activity after the im plantation of KPro material into the rabbit cornea. Methods. Poly(2-hy droxyethyl methacrylate) sponge pieces were implanted into rabbit corn eas. Prednisolone, tetracycline, medroxyprogesterone, acetylcysteine, and sodium citrate were assessed for effects on gelatinolytic activity and stromal collage nase [matrix metalloprotease-1 (MMP-1)] productio n in vivo and in vitro by using zymography and Western blotting techni ques. Results. Whereas all five anticollagenase drugs were effective i n reducing gelatinolytic activity in vitro, many were ineffective in v ivo. However, medroxyprogesterone caused a reduction of gelatinolytic activity in vivo. The amount of MMP-1, as measured by immunoblotting, also was reduced by medroxyprogesterone treatment when compared with u ntreated controls. An increase in the apparent molecular weight of MMP -1 in operated corneas appears to be the result of the association of MMP-1 with collagen fragments resulting from the surgical trauma. Conc lusion. This study indicates that topical medroxyprogesterone may be a useful adjunctive therapy after prosthokeratoplasty.