Inhibition of [alpha]5[beta]1-integrin significantly improves the surgical outcome of glaucoma surgery in mice compared to MMC

• Published in: Acta ophthalmologica (Oxford, England) Vol. 92; no. s253
• Main Authors: Van Bergen, T, Zahn, G, Caldirola, P, Fsadni, M, CARAM-LELHAM, N, Vandewalle, E, Stalmans, I
• Format: Journal Article
• Language: English
• Published: Malden Wiley Subscription Services, Inc 01-09-2014
• Subjects: Ophthalmology
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2014.1733.x

Purpose The aim of this study was to evaluate the therapeutic potential of [alpha]5[beta]1-integrin inhibitor (CLT-28643) to improve the outcome of filtering surgery in a mouse model. Different dose regimen and administration routes of the inhibitor were compared to mitomycin C (MMC), the gold standard in clinical practice. Methods The efficacy of CLT-28643 on surgical outcome was studied in a mouse model for filtering surgery (n=40 eyes from 20 mice per group). Group 1 received a single subconjunctival (SC) injection of 2 µg of the integrin inhibitor immediately after surgery, whereas repeated SC injections were administered on day 0, 3, 7, 14 and 21 in groups 2 and 3 (2 and 1 µg, respectively). Group 4 received topical eye drops containing 10 µg of the compound 3 times daily. MMC 0.02% was applied for 2 minutes in group 5 and repeated SC injections of NaCl were given in the last group. Treatment outcome was studied by a masked observer every other day by clinical investigation of the bleb until postoperative day 28. Results Surgical outcome was improved in all treatment groups compared to NaCl treated eyes (P<0.001). A dose-response curve was observed in the efficacy of the subconjunctival injections, with the repetitive administration of 1µg being significantly inferior to, the single injection of 2 µg or topical administration (10 µg) comparable to, and the repetitive injection of 2 µg significantly superior to MMC. Conclusion These data suggest that administration of the [alpha]5[beta]1-integrin inhibitor CLT-28643 has therapeutic potential as an adjunct to glaucoma surgery, possibly with a superior efficacy to MMC when used at the optimal dose. [PUBLICATION ABSTRACT]