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Khaled M. Nassar, Ayeguel Tura, Matthias Lüke, Julia Lüke, Aizhan Tapenbayeva, Salvatore Grisanti; Antifibrotic Effects Of "LY364947", a Potent ATP Competitive Inhibitor Of The TGF-ß Type I Receptor, On Scar Formation After Glaucoma Surgery. Invest. Ophthalmol. Vis. Sci. 2011;52(14):617.
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To explore the antifibrotic effects of "LY364947" on scar formation after glaucoma filtrating surgery.
The half maximal inhibitory concentration (IC50) of LY364947 in the human tenon’s fibroblast proliferation was determined by XTT test. On 20 chinchilla rabbits (Crl:CHB), glaucoma filtration surgery similar to clinical practice, was performed. The animals received either no adjuvant, one unilateral subconjunctival injection of LY364947 (5 µmol, 50 µmol), or the vehicle alone at baseline. The bleb was scored with the Indiana Bleb Appearance Grading Scale. Intraocular pressure (IOP) measurements were performed in triplicate. The difference in measured IOP was expressed as the right to-left (R/L) eye ratio. The animals were sacrificed on day 14 and the eyes processed for histology and immunohistochemical staining for alpha smooth muscle actin (alpha SMA). The amount of fibrosis was quantified using JMicrovision software.
Both the vehicle and the LY364947 solution were well tolerated. No adverse effects such as inflammation or blurring of the optical media were observed. Conjunctival scarification occurred within 1 week in the control groups but was suppressed in the experimental groups. The intraocular pressure correlated with the fibrotic process and reached normal levels within 7 days after surgery in control animals, but remained significantly (P < 0.001) reduced in the experimental groups until the end of the follow up time. Histologic examination of the surgical area 14 days after surgery disclosed massive fibrosis in the control animals, but little deposition of extracellular matrix in the experimental groups.
In this rabbit model of glaucoma filtrating surgery, intraoperative subconjunctival LY364947 application significantly reduces conjunctival scarring and improves surgical outcome of glaucoma filtration treatments in rabbits.
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