Taurine deficiency induces retinal inflammation

Abstract

Purpose : We recently showed that taurine deficiency induced the selective and concomitant degeneration of cone photoreceptors and retinal ganglion cells (RGC) (Hadj-Saïd et al., IOVS 2016; 57:4692-4703). We investigate here if the degenerative process may trigger retinal gliosis with microglial activation and their migration into the photoreceptor layers.

Methods : We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion. Retinas were dissected as wholemounts and immunolabelled for Iba1 (microglia) and PNA (cones). The retinal distribution of microglia was studied using 3D images from confocal microscopy. Retinal inflammation was also examined on retinal sections to define the relationship of microglial cells to apoptotic cells (Tunnel Assay).

Results : In retinal sections, microglial cells were often observed in the outer layer (ONL) in GES-treated mice whereas they were not found in the same layer in non-treated mice. This abnormal distribution of microglial cells in the ONL was also clearly detectable on retinal flatmounts. This flatmount strategy enabled us to generate a systematic counting approach to quantify the drastic ongoing inflammation so that we can then assess therapeutic treatments. Furthermore, these observations provide a more integrated examination of the whole microglial populations and its relationship to blood vessel or degenerating cone photoreceptors. The complete cell morphology is also better appreciated showing the cell budging, which is another evidence of the microglial activation.

Conclusions : This study demonstrates that taurine depletion causes microglial activation and migration and establishes a relation of cone loss and microglial migration to the ONL of retina. These results question if the retinal inflammation is consecutive to the photoreceptor degeneration from GES-treated mice.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.