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Vivian Choh, Gah-Jone Won, Douglas S. Fudge; The Effects of a Myosin Light Chain Kinase Inhibitor on the Stiffness of Avian Crystalline Lenses. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6650.
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It has been shown that the posterior fibre cells anchored at the lens capsule are associated with proteins such as actin, myosin and N-cadherins. Together, these proteins form a hexagonal lattice cradling the posterior surface of the lens. This study was undertaken to investigate whether disrupting myosin can affect the structural integrity of avian crystalline lenses.
Lenses of 7-day-old White Leghorn chickens (Gallus gallus domesticus; n=14 birds) were treated with either 100 µM of a myosin light chain kinase inhibitor, 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7) or 100 µM of dimethyl sulfoxide (ML-7 vehicle). Structural integrity, assessed as the mechanical response of the lens to compression, was tested using an instrument that compresses the lens while measuring the responding force. Mechanical trials consisted of compression (loading) and decompression (unloading) of the lens, repeated 3 times, and for 3 different compression levels (0.75 mm, 1.0 mm and 1.25 mm). Stiffness was measured from the slope of the initial, linear portion of the exponential loading curve. Resilience, the ability of the lens to store energy, was calculated as the ratio of the total area under the unloading curve to the total area under the loading curve.
Compressions greater than 1.0 mm resulted in bursting of six ML-7-treated lenses, therefore 0.75 mm data were used for analysis of stiffness and resilience. No vehicle-treated lenses ruptured. Loading curves for ML-7-treated lenses were steeper, indicating greater stiffness. The stiffness in ML-7-treated eyes was significantly higher than that for vehicle-treated eyes (p=0.0371; 15.84 ± 21.30 mN/mm vs. 3.95 ± 3.58 mN/mm, respectively). No differences were detected for resilience between the two treatment groups (p=0.1369; 71.86% ± 10.23% and 80.47% ± 18.56%, respectively).
ML-7 caused a large increase in lenticular stiffness and also appeared to make the lenses more prone to bursting. It remains unclear whether increased stiffness is a normal response for this myosin light chain kinase inhibitor. Excessive doses of ML-7 have been shown to inhibit other protein kinases in other cellular systems, thus the results observed in this study might indicate inhibition of additional kinases. Future experiments will include the use of different concentrations, and determination of which protein kinases are affected by ML-7.
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