Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion

Abstract

Citation: Hadj-Saïd W, Froger N, Ivkovic I, et al. Quantitative and topographical analysis of the losses of cone photoreceptors and retinal ganglion cells under taurine depletion. Invest Ophthalmol Vis Sci. 2016;57:4692-4703. DOI:10.1167/ iovs.16-19535 PURPOSE. Taurine depletion is known to induce photoreceptor degeneration and was recently found to also trigger retinal ganglion cell (RGC) loss similar to the retinal toxicity of vigabatrin. Our objective was to study the topographical loss of RGCs and cone photoreceptors, with a distinction between the two cone types (S-and L-cones) in an animal model of induced taurine depletion. METHODS.We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion at a concentration of 1% in the drinking water. Spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were performed on animals after 2 months of GES treatment administered through the drinking water. Retinas were dissected as wholemounts and immunodetection of Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number of Brn3a þ RGCs, and L-and S-opsin þ cones was automatically quantified and their retinal distribution studied using isodensity maps. RESULTS.The treatment resulted in a significant reduction in plasma taurine levels and a profound dysfunction of visual performance as shown by ERG recordings. Optical coherence tomography analysis revealed that the retina was thinner in the taurine-depleted group. Sopsin þ cones were more affected (36%) than L-opsin þ cones (27%) with greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly distributed.CONCLUSIONS. This study confirms that taurine depletion causes RGC and cone loss. Electroretinograms results show that taurine depletion induces retinal dysfunction in photoreceptors and in the inner retina. It establishes a gradient of cell loss depending on the cell type from S-opsin þ cones, L-opsin þ cones, to RGCs. The greater cell loss in the dorsal retina and of the S-cone population may underline different cellular mechanisms of cellular degeneration and suggests that S-cones may be more sensitive to light-induced retinal toxicity enhanced by the taurine depletion.

Taurine Depletion Causes ipRGC Loss and Increases Light-Induced Photoreceptor Degeneration

“…This is in accordance with previous publications that document an earlier cone loss, and minimal rod loss, in taurine-depleted animals. 6 In addition to cone loss, control light-exposed animals also showed a disruption of the normal photoreceptor mosaic: ''empty rings'' devoid of both types of cones (Fig. 6) appeared mainly in the superotemporal retina, in an area coincident with the ''arciform photosensitive area'' previously described by our group [18][19][20] (Fig.…”

“…The endogenous synthesis of taurine can be insufficient, because in cats 2 and in monkeys 3 nutritional taurine depletion has been shown to cause photoreceptor degeneration. Recently it has been documented that taurine depletion also causes retinal ganglion cell (RGC) loss, [4][5][6] and therefore retinal health is dependent on taurine, at least in some species.…”

“…Chronic pharmacological treatment with b-alanine or guanidoethane sulfonate (GES) is necessary to induce taurine depletion in rodents, 1,6,[12][13][14] because their endogenous taurine synthesis is higher than in other species, such as cats, humans, or monkeys. 1,12 In mice, we have documented that the topography of photoreceptor loss induced by taurine depletion resembles that observed after light damage, as it is greater in the dorsal retina.…”

“…1,12 In mice, we have documented that the topography of photoreceptor loss induced by taurine depletion resembles that observed after light damage, as it is greater in the dorsal retina. 6 Several authors have suggested a direct relationship between taurine depletion and light sensitivity of retinal neurons. 6,10,[15][16][17] Thus, the question arises whether retinal degeneration triggered by taurine depletion is greater after light exposure (ALE).…”

“…6 Several authors have suggested a direct relationship between taurine depletion and light sensitivity of retinal neurons. 6,10,[15][16][17] Thus, the question arises whether retinal degeneration triggered by taurine depletion is greater after light exposure (ALE).…”