Matrix metalloproteinase inhibition modulates postoperative scarring after experimental glaucoma filtration surgery.
OBJECTIVE
To determine whether postoperative application of a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM6001 (ilomastat), reduces scarring after glaucoma filtration surgery.


METHODS
In a randomized, prospective, masked-observer study, 40 New Zealand White rabbits underwent modified glaucoma filtration surgery. The animals were randomly allocated to receive postoperative subconjunctival injections of either phosphate-buffered saline (PBS) or 100 microM ilomastat for 10 days. The animals were killed on days 7, 14, 21, and 30. Clinical characteristics, which included bleb morphology and intraocular pressure, were recorded. Tissue sections were immunohistochemically stained for alpha smooth muscle actin (alphaSMA) and extracellular matrix components in the two groups.


RESULTS
Surgical outcome was significantly prolonged in the ilomastat-treated group compared with the vehicle-treated group (P < 0.001). At day 30, all the blebs had survived except two in the ilomastat-treated group, whereas no blebs survived to day 30 with vehicle treatment (n = 11). The intraocular pressure remained significantly lower throughout the course of the experiment in the ilomastat group compared with the vehicle group (P < 0.0017). Histologically, less scar tissue was observed at the sclerostomy site with inhibition of MMP, compared with vehicle treatment.


CONCLUSIONS
The data presented suggest that the healing response after surgery can be modulated by inhibiting the effects of MMPs. Inhibition of MMP significantly improved surgical outcome by reducing the amount of scar tissue produced. By targeting the actions of these proteolytic enzymes, a more controlled and physiological method of modulating scarring may be achieved.
Wong
Tina T L
TT
Wound Healing Research Unit, Department of Pathology, Institute of Ophthalmology, London, United Kingdom. tina.wong@ucl.ac.uk
Mead
Anna L
AL
Khaw
Peng T
PT
D000199:Actins / Q000378:metabolism; D000818:Animals; D002921:Cicatrix / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018463:Filtering Surgery; D005901:Glaucoma / Q000201:enzymology / Q000473:pathology / Q000601:surgery*; D006877:Hydroxamic Acids; D007211:Indoles / Q000494:pharmacology; D007267:Injections; D007429:Intraocular Pressure; D061965:Matrix Metalloproteinase Inhibitors; D011183:Postoperative Complications / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D014945:Wound Healing
D000199:Actins; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D061965:Matrix Metalloproteinase Inhibitors; C119203:ilomastat