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α 5 β 1‐Integrin inhibitor ( CLT ‐28643) effective in rabbit trabeculectomy model
Author(s) -
Schultheiss Maximilian,
Schnichels Sven,
Konrad EvaMaria,
BartzSchmidt Karl U.,
Zahn Grit,
Caldirola Patrizia,
Fsadni Mario G.,
CaramLelham Ninus,
Spitzer Martin S.
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.13215
Subject(s) - trabeculectomy , medicine , bleb (medicine) , intraocular pressure , fibrosis , vascularity , ophthalmology , surgery , glaucoma , pathology
Purpose Glaucoma filtration surgery ( GFS ) fails due to fibrosis. The α 5 β 1‐integrin plays a pivotal role in fibrosis, angiogenesis and inflammation. This is the first experiment evaluating the prevention of fibrosis after GFS by a specific small molecule α 5 β 1‐integrin inhibitor ( CLT ‐28643). Methods Twenty‐four rabbits received trabeculectomy on their right eyes. The rabbits were randomized into three groups of eight eyes each. CLT ‐28643 was given as a single subconjunctival injection intraoperatively to two of the right eye groups followed by postoperative vehicle eye drops ( CLT + group) or CLT ‐28643 eye drops 4 times daily ( CLT ++ group). A third group received mitomycin‐C ( MMC ) intraoperatively (sponge application, 0.04%, 2 min) followed by vehicle eye drops postoperatively. The control‐surgery group consisted of 12 left eyes having trabeculectomy with no adjunctive therapy. The remaining 12 left eyes formed the untreated group. Clinical assessment included intraocular pressure ( IOP ) measurement, slit‐lamp examination (including bleb survival and morphology) and bleb photography. The rabbits were killed after four weeks for histology. Results Both CLT ‐28643‐treated groups showed significantly prolonged bleb survival, and better bleb score compared to the control‐surgery group. At end of the study, most functioning blebs were found in the MMC group ( MMC group 75%; CLT + group 12.5%, CLT ++ group 25%; CLT + group 12.5%, control‐surgery group 0%). CLT ‐28643 was non‐toxic and well tolerated. Conclusions This rabbit GFS study indicates that inhibition of α 5 β 1‐integrin by the novel α 5 β 1‐integrin antagonist CLT ‐28643 significantly improved the outcome. The effect of a single intro‐operative application of CLT ‐28643 seems to be inferior to 0.04% MMC .