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Jieming Fu, Moe Aung, Megan Prunty, Adam Hanif, Jeffrey H Boatright, Machelle T Pardue; Tauroursodeoxycholic Acid Protects Visual Function in a Mouse Model of Type 1 Diabetes. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have demonstrated the efficacy of tauroursodeoxycholic acid (TUDCA) in preserving visual function in mouse models of retinitis pigmentosa (Boatright et al., 2006) and preventing apoptosis in retinal neurons cultured in hyperglycemic conditions (Gaspar et al., 2013). This study tested the hypothesis that TUDCA will preserve retinal function and prevent neuronal apoptosis in a mouse model of diabetic retinopathy (DR).
Adult C57BL/6 mice were made diabetic at 8-10 weeks of age via injection of streptozotocin. Diabetes was confirmed by serially elevated blood glucose (>250 mg/dl; DM). Mice were randomly sorted into early or late treatment paradigms: biweekly TUDCA injections starting either one week (n=13) or three weeks (n=12) after confirmation of hyperglycemia to create 4 treatment groups: ctrl+veh, ctrl+TUDCA, DM+veh, DM+TUDCA. Assessment of visual function was done via a virtual optokinetic tracking system at 4, 6, 8, and 10 weeks after induction of diabetes, as well as scotopic electroretinograms (specifically oscillatory potentials; OPs) at 4 and 8 weeks after induction of diabetes.
DM mice showed significantly decreased spatial frequency thresholds compared to Ctrl mice, while early TUDCA treatment showed preservation at all timepoints (wk 10, ctrl: 0.39 ±0.004 c/d, DM+veh: 0.35 ±0.01 c/d, DM+early TUDCA: 0.39 ±0.01 c/d; mean ±sem, p<0.001). Similarly, contrast sensitivity decreased in DM mice at 8 and 10 weeks compared to ctrls and early TUDCA treatment ameliorated this decline (wk 10, ctrl: 6.4 ±0.28%, DM+veh: 4.28 ±0.32%, DM+early TUDCA: 6.23 ±0.30%; p<0.001). OP2 amplitudes decreased in DM mice compared to ctrls with early TUDCA treatment eliminating this decline (wk 4 to 0.06 cd s/m2 stimuli; ctrl: 186 ±17 µV, DM+veh: 88.06 ±21 µV, DM+early TUDCA: 159 ±17 µV; p<0.001). Importantly, the early treatment group showed no significant differences from the control group for spatial frequency and contrast sensitivity thresholds, or OP2 amplitudes. Late TUDCA treatment mice showed no statistically significant preservation.
TUDCA preserves visual function in an STZ-mouse model of Type I diabetes. Reducing the time interval between induction of diabetes and start of treatment is crucial in obtaining TUDCA’s neuroprotective effects. TUDCA may be an effective, clinically translational intervention against declining visual function caused by diabetic retinopathy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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