INSERM, CNRS, Institut de La Vision, Sorbonne Université, 17 Rue Moreau, 75012, Paris, France.
Institut de Recherches Servier, 125 Chemin de Ronde, 78290, Croissy-Sur-Seine, France.
Acta Neuropathol Commun. 2023 Jan 11;11(1):5. doi: 10.1186/s40478-022-01489-3.
Tauopathies, including Alzheimer's disease, are characterized by retinal ganglion cell loss associated with amyloid and phosphorylated tau deposits. We investigated the functional impact of these histopathological alterations in the murine P301S model of tauopathy. Visual impairments were demonstrated by a decrease in visual acuity already detectable at 6 months, the onset of disease. Visual signals to the cortex and retina were delayed at 6 and 9 months, respectively. Surprisingly, the retinal output signal was delayed at the light onset and advanced at the light offset. This antagonistic effect, due to a dysfunction of the cone photoreceptor synapse, was associated with changes in the expression of the vesicular glutamate transporter and a microglial reaction. This dysfunction of retinal glutamatergic synapses suggests a novel interpretation for visual deficits in tauopathies and it highlights the potential value of the retina for the diagnostic assessment and the evaluation of therapies in Alzheimer's disease and other tauopathies.
tau 病包括阿尔茨海默病，其特征是视网膜神经节细胞丧失与淀粉样蛋白和磷酸化 tau 沉积物相关。我们研究了在 P301S tau 病小鼠模型中这些组织病理学改变的功能影响。在疾病发作的 6 个月时，就已经可以通过视力下降来证明视力障碍。视觉信号到皮质和视网膜的分别在 6 个月和 9 个月时延迟。令人惊讶的是，视网膜输出信号在光起始时延迟，在光结束时提前。这种拮抗作用是由于视锥光感受器突触功能障碍引起的，与囊泡谷氨酸转运体的表达变化和小胶质细胞反应有关。视网膜谷氨酸能突触的这种功能障碍为 tau 病中的视觉缺陷提供了一个新的解释，并突出了视网膜在阿尔茨海默病和其他 tau 病的诊断评估和治疗评估中的潜在价值。
