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Margaret Garner, William H Garner, William Burns; Dioptin™ Eye Drop Increases Mouse Lens Elasticity. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3767.
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To correlate lipoic acid (LA)-dependent disulfide reduction and lens elasticity and to characterize the effects of the choline ester of LA (LACE) on lens elasticity.
Eight month old mouse lenses (C57BL/6J) were incubated for 12 hours in medium supplemented with selected levels (0 - 500uM) of lipoic acid (LA). Lens elasticity was measured using the coverslip method (Experimental Eye Research 91 (2010) 300-307). After elasticity measurements lenses were homogenized in a dissociation medium containing alkylating agent 1 (free SH modification). The homogenate was filtered and the rinsed, resuspended, retentate was treated with reducing agent (TCEP) and alkylating agent 2 (S-S SHs modified). After filtration and rinses, the levels of alkylated SH groups in retentate 2 was determined. Bovine serum albumin was the positive control for the sulfhydryl analysis. LACE was designed to improve topical ocular delivery of LA to the lens. Eight month old C57BL/6J mice were treated with 2.5uL of a formulation of 5% LACE (Dioptin™) three times per day at eight hour intervals in the right eye (OD) for 5 weeks. After the final treatment, lenses were removed and placed in a cuvette containing HBSS. Elasticity was determined with a computer controlled instrument that provided Z stage upward movements in 1um increments with concomitant force measurements with a Harvard Apparatus F10 isometric force transducer. The elasticity of lenses from 8 week old C57BL/6J mice was determined for comparison.
LA treatment led to a concentration-dependent decrease in lens protein disulfides concurrent with an increase in lens elasticity. Changes in disulfides and elasticity were negatively correlated (R=0.87, p=0.006). The [LA]50 for both effects was 50±10uM with maximal effect at 100uM LA. After topical ocular treatment with Dioptin™ the lenses of the treated eyes of the old mice were more elastic than the lenses of untreated eyes, i.e. the relative force required for similar Z displacements was higher in the untreated eyes’ lenses. In most instances the lenses of the treated eyes were even more elastic than the lenses of the 8 week old mice.
As the peri-central elasticity of the human lens decreases with age, humans lose the ability to accommodate. The results, briefly described in this abstract suggest a topical ocular treatment that increases lens elasticity through reduction of disulfides will, concomitantly, restore accommodative amplitude.
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