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Jana T Sellers, Micah A Chrenek, Nathaniel F Henneman, Jeffrey H Boatright; TUDCA and DMSO additively protect against light-induced retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):254. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
When given systemically and individually, tauroursodeoxycholic acid (TUDCA) and dimethyl sulfoxide (DMSO) are protective in the Light-Induced Retinal Degeneration (LIRD) mouse model, putatively via different mechanisms of action. DMSO is FDA-approved for treatment of interstitial cystitis, but can be neurotoxic and is thought to damage lens cortical fibers. Here we tested whether combinations of lower doses of systemically-injected DMSO and TUDCA are additively protective in the LIRD mouse model.
Male Balb/cAnNCrl mice, aged 71 days, were injected IP with two different solutions (below), dark adapted overnight, injected again the following morning, then exposed to 4 h of high-intensity (3,000 lux) or dim (50 lux) light. The injection combinations were as follows: 100 mg/kg TUDCA in sodium bicarbonate (SBC) and 2.1 ml/kg DMSO in Dulbecco’s PBS (DPBS), 300 mg/kg TUDCA and 3.2 ml/kg DMSO, 100 mg/kg TUDCA and DPBS, 300 mg/kg TUDCA and DPBS, 2.1 ml/kg DMSO and SBC, 3.2 ml/kg DMSO and SBC, and DPBS and SBC. To assess retina function, electroretinograms (ERGs) were taken one week after light exposure.
Exposure to 3,000 lux light significantly diminished ERG a- and b- wave amplitudes (p<0.0001, 2 way AVOVA with Tukey post-hoc analysis). Treatment with 3.2 ml/kg DMSO only partially prevented this loss, with ERG amplitudes of this treatment group significantly greater than vehicle-treated mice exposed to 3,000 lux light (p<0.0001), but also significantly less than those of mice exposed to dim light (p=0.0002). However, combining this same dose of DMSO with IP injection of 300 mg/kg TUDCA, a TUDCA dose that alone had no protective effect, completely preserved ERG amplitudes, with no diminution at all due to toxic light exposure.
Combinations of lower doses of systemically-injected DMSO and TUDCA were additively protective in the LIRD mouse model. It may be that several FDA-approved drugs can be made to be beneficial in the ophthalmic clinic if their potential toxicities are managed by co-administration of neuroprotectants such as TUDCA.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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