Visual phenotyping in mutant mice deleted for the taurine-transporter gene

Abstract

Purpose: In the 70s, taurine was shown to induce photoreceptor degeneration. This rod and cone degeneration was also shown is in knockout mice for the taurine transporter (Tau-T KO), which takes up taurine into tissues and cells. More recently, by investigating the retinal phototoxicity of vigabatrin, we found that this antiepileptic drug induces a taurine depletion. It led us to discover that both retinal ganglion cells and cone photoreceptors appear as the primary sites of damage in albino adult taurine-depleted animals. We have here further investigated the visual phenotype of the Tau-T KO mouse.

Methods: Visual acuity was evaluated by optokinetics tests, retinal cell function was measured by electroretinogram (ERG) recordings on heterozygous (HT) and homozygous (HO) Tau-T KO mice as compared to wild-type C57BL/6J mice (WT). Cell loss was examined in vivo, using optic coherence tomography (OCT). Histological examinations were then performed on both retinal sections and retinal flatmounts to quantify photoreceptors and retinal ganglion cells (RGC).

Results: The deletion of gene encoding for Tau-T caused a marked depletion of plasma taurine concentrations In HO mice (371±6 µM, 771±176 µM and 732±40 µM for HO, HT and WT mice, respectively). Interestingly, the mutation induced severe impairment of visual function since the optokinetic score was reduced in HO mice compared to WT mice, while the HT mice were unaffected. Such visual impairments were correlated to changes in electroretinograms. Indeed, retinal function in the rod and cone pathways was rapidly abolished in HO mice as indicated by both scotopic and photopic ERG measurements. OCT imaging indicated a reduction of the total retinal thickness with a loss of the photoreceptors layers in HO mice. Histology showed a cone loss, whereas RGC density appeared unaffected in 9-week HO mice.

Conclusions: These data showed that the absence of Tau-T leads to a profound retinal degeneration, with a primary photoreceptor disruption, due to the taurine depletion. Because the RGC loss was only found in taurine-depleted albino animals, the absence of RGC loss in the pigmented tau-T KO mice is consistent with the notion of RGC phototoxicity. Further studies will investigate the light phototoxicity to RGCs in tau-T KO mice. These data further demonstrate the crucial role of the Tau-T for maintaining the visual function.

Keywords: 695 retinal degenerations: cell biology • 494 degenerations/dystrophies • 740 transgenics/knock-outs