Effect of tauroursodeoxycholic acid on retinal degeneration in rd10 mice

Abstract

Abstract: : Purpose: Tauroursodeoxycholic acid (TUDCA) is a naturally–occurring bile acid that is neuroprotective in models of neurological disease. We tested whether TUDCA was similarly protective in the rd10 mouse, an animal model of retinal degeneration. Methods: Mice were injected subcutaneously with TUDCA or vehicle (NaHCO₃) during development. At postnatal day 18 (PN18), electroretinograms (ERGs) were measured and mice were killed and their eyes harvested and fixed. Eyes were sectioned, sections stained (H & E or toluidine blue), and retina cell layers morphometrically analyzed by light microscopy. Consecutive sections were subjected to modified TUNEL. Results: Retinas of TUDCA–treated mice had thicker outer nuclear layers, more photoreceptor cells, more fully–developed photoreceptor outer segments, and fewer TUNEL–positive cells compared to those treated with vehicle. ERG a–wave and b–wave amplitudes were greater in mice treated with TUDCA compared to those treated with vehicle. ERG, morphometric, and TUNEL differences were statistically significant. No deleterious effects were observed with TUDCA or vehicle injections. Conclusions: TUDCA treatment partially prevented photoreceptor degeneration and loss of visual function in rd10 mice at PN18, possibly by suppressing apoptosis.

Keywords: apoptosis/cell death • pharmacology • photoreceptors