minocycline and Corneal-Diseases

OBJECTIVE To compare the efficacy of various concentrations and combinations of serum, EDTA, 3 tetracyclines, and N-acetylcysteine (NAC) for collagenase inhibition in an in vitro corneal degradation model. SAMPLE Grossly normal corneas from recently euthanized dogs and horses and fresh serum from healthy dogs and horses. PROCEDURES Serum was pooled by species for in vitro use. For each species, sections of cornea were dried, weighed, and incubated with clostridial collagenase (800 U/mL) in 5 mL of a 5mM calcium chloride-saline (0.9% NaCl) incubation solution and 500 μL of 1 of 19 treatments (homologous serum; 0.3%, 1.0%, or 2% EDTA; 0.1%, 0.5%, or 1.0% tetracycline, doxycycline, or minocycline; 0.5%, 1.0%, or 5.0% NAC; serum with 0.5% tetracycline; serum with 1.0% EDTA; or 1.0% EDTA with 0.5% tetracycline). Positive and negative control specimens were incubated with 5 mL of incubation solution with and without collagenase, respectively. Each control and treatment was replicated 4 times for each species. Following incubation, corneal specimens were dried and reweighed. The percentage corneal degradation was calculated and compared among treatments within each species. RESULTS Treatments with tetracyclines at concentrations ≥ 0.5%, with EDTA at concentrations ≥ 0.3%, and with NAC at concentrations ≥ 0.5% were more effective at preventing corneal degradation than serum in both species. The efficacy of each combination treatment was equal to or less than that of its components. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested EDTA, tetracyclines, and NAC may be beneficial for topical treatment of keratomalacia, but in vivo studies are required.

Topics: Acetylcysteine; Animals; Anti-Bacterial Agents; Collagenases; Cornea; Corneal Diseases; Disease Models, Animal; Dogs; Doxycycline; Edetic Acid; Horses; Matrix Metalloproteinase Inhibitors; Minocycline; Serum; Tetracycline

We describe a new inhibitor of angiogenesis, minocycline, a semisynthetic tetracycline antimicrobial with anticollagenase properties. Minocycline was incorporated into controlled release polymers and tested in the rabbit cornea against neovascularization in the presence of the VX2 carcinoma. Inhibition by minocycline was shown to be comparable to that of the combination of heparin and cortisone, a potent inhibitor of angiogenesis. Minocycline decreased tumor-induced angiogenesis by a factor of 4.5, 4.4, and 2.9 at 7, 14, and 21 days, respectively. At the end of the experiment, whereas the corneas with empty polymers had large, invasive, exophytic tumors, none of the corneas with minocycline had such vascular masses. Recently, studies of agents that disrupt collagen synthesis and deposition have yielded several new angiogenesis inhibitors. We suggest that investigation of agents that disrupt collagenolysis may similarly identify other angiogenesis inhibitors and further clarify the mechanisms of angiogenesis.

Topics: Animals; Antineoplastic Agents; Cornea; Corneal Diseases; Cortisone; Eye Neoplasms; Heparin; Minocycline; Neovascularization, Pathologic; Rabbits