Assessment of anticollagenase treatments after insertion of a keratoprosthetic material in the rabbit cornea.
OBJECTIVE
This study was performed to evaluate the enzyme production in response to implantation of the hydrogel material used in the experimental Chirila keratoprosthesis (KPro) and to assess the effects of five topical drugs on enzyme production and activity. KPros may be extruded from the cornea as a result of tissue melting, a process that involves excessive enzyme activity. To reduce the possibility of implant loss for the hydrogel Chirila KPro, a number of antiinflammatory drugs that have been used to treat other corneal melting conditions were investigated for their effect on initial collagenase activity after the implantation of KPro material into the rabbit cornea.


METHODS
Poly(2-hydroxyethyl methacrylate) sponge pieces were implanted into rabbit corneas. Prednisolone, tetracycline, medroxyprogesterone, acetylcysteine, and sodium citrate were assessed for effects on gelatinolytic activity and stromal collagenase [matrix metalloprotease-1 (MMP-1)] production in vivo and in vitro by using zymography and Western blotting techniques.


RESULTS
Whereas all five anticollagenase drugs were effective in reducing gelatinolytic activity in vitro, many were ineffective in vivo. 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 untreated 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.


CONCLUSIONS
This study indicates that topical medroxyprogesterone may be a useful adjunctive therapy after prosthokeratoplasty.
Fitton
J H
JH
Lions Eye Institute, Perth, Western Australia.
Ziegelaar
B W
BW
Hicks
C R
CR
Clayton
A B
AB
Crawford
G J
GJ
Constable
I J
IJ
Chirila
T V
TV
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology; D000287:Administration, Topical; D000818:Animals; D015153:Blotting, Western; D002951:Citrates / Q000008:administration & dosage / Q000494:pharmacology; D017364:Collagenases / Q000378:metabolism; D003315:Cornea / Q000187:drug effects* / Q000201:enzymology / Q000601:surgery; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D018093:Gelatinases / Q000378:metabolism; D006085:Graft Survival; D020007:Implants, Experimental; D061965:Matrix Metalloproteinase Inhibitors; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000494:pharmacology; D008689:Methacrylates; D009883:Ophthalmic Solutions; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D000077559:Sodium Citrate; D013752:Tetracycline / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome
D002951:Citrates; D061965:Matrix Metalloproteinase Inhibitors; D008689:Methacrylates; D009883:Ophthalmic Solutions; D000077559:Sodium Citrate; C005044:hydroxyethyl methacrylate; D011239:Prednisolone; D017364:Collagenases; D018093:Gelatinases; D013752:Tetracycline; D008525:Medroxyprogesterone; D000111:Acetylcysteine