Focal scleral permeability enhanced by collagenase digestion. Experimental model of enzymatic sclerostomy.
OBJECTIVE
The purpose of this study is to demonstrate that restricted application of clostridial collagenase to the animal sclerolimbal area produces increased tissue permeability in vitro and results in a lasting significant decrease in the intraocular pressure (IOP) in vivo.


METHODS
A special miniature device was developed to apply the carefully characterized enzyme to a small (1-mm diameter) and defined sclerolimbal area isolated from the surrounding tissue. The device was applied to the rabbit limbus for 4 hours and then removed. The enzyme was inactivated and washed out with an inhibitory solution. The IOP was measured by pneumotonometry, and the treated tissue was investigated by light and electron microscopy. Application and removal of the drug-delivery microapplicator was performed under topical anesthesia.


RESULTS
Enzymatic degradation propagated without lateral spreading and reached at least two thirds of tissue width. Results of histologic examination of the treated area showed a thin tissue, characterized by degraded and disorganized collagen fibers, which were sharply separated from the intact fibers in the untreated area. This was sufficient to cause a tenfold increase in the basic transscleral flow in vitro, and a significant, relatively long-lasting (> 30 days) lowering of the mean IOP in 15 albino rabbits. In the first 10-day period after treatment, the IOP was reduced by 40%, and during the rest of the follow-up the IOP remained lowered by more than 20% (P > 0.0001) without any adjuvant treatment.


CONCLUSIONS
Despite the small size of the collagenase-affected tissue, the evacuation rate of the aqueous humor was sufficient to cause a significant and relatively long-lasting lowering of IOP in rabbits. This mild treatment, performed under topical anesthesia, might present the basis for the development of an ambulatory treatment of human glaucoma.
Dan
J A
JA
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Yaron
A
A
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002417:Cattle; D002463:Cell Membrane Permeability; D003094:Collagen / Q000378:metabolism / Q000648:ultrastructure; D017364:Collagenases / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000295:instrumentation; D007429:Intraocular Pressure; D009798:Ocular Hypertension / Q000628:therapy*; D011817:Rabbits; D012590:Sclera / Q000378:metabolism* / Q000648:ultrastructure; D012599:Sclerostomy / Q000379:methods*
D003094:Collagen; D017364:Collagenases