Autism spectrum disorders (ASD) affect around 1.5% of people worldwide. Symptoms start around age 2, when children fail to maintain eye contact and to develop speech and other forms of communication. Disturbances in glutamatergic and GABAergic signaling that lead to synaptic changes and alter the balance between excitation and inhibition in the developing brain are consistently found in ASD. One of the hallmarks of these disorders is hypersensitivity to sensory stimuli; however, little is known about its underlying causes. Since the retina is the part of the CNS that converts light into a neuronal signal, we set out to study how it is affected in adolescent mice prenatally exposed to valproic acid (VPA), a useful tool to study ASD endophenotypes. Pregnant female mice received VPA (600 mg/kg, ip) or saline at gestational day 11. Their male adolescent pups (P29–35) were behaviorally tested for anxiety and social interaction. Proteins known to be related with ASD were quantified and visualized in their retinas by immunoassays, and retinal function was assessed by full-field scotopic electroretinograms (ERGs). Early adolescent mice prenatally exposed to VPA displayed impaired social interest and increased anxiety-like behaviors consistent with an ASD phenotype. The expression of GABA, GAD, synapsin-1, and FMRP proteins were reduced in their retinas, while mGluR5 was increased. The a-wave amplitudes of VPA-exposed were smaller than those of CTR animals, whereas the b-wave and oscillatory potentials were normal. This study establishes that adolescent male mice of the VPA-induced ASD model have alterations in retinal function and protein expression compatible with those found in several brain areas of other autism models. These results support the view that synaptic disturbances with excitatory/inhibitory imbalance early in life are associated with ASD and point to the retina as a window to understand their subjacent mechanisms.

中文翻译：

---

自闭症谱系障碍的临床前模型中的视网膜改变

自闭症谱系障碍（ASD）影响全球约1.5％的人。当儿童无法保持眼神交流并发展言语和其他形式的交流时，症状就会在2岁左右开始出现。在ASD中始终发现谷氨酸能和GABA能信号的干扰会导致突触变化并改变发育中的大脑的兴奋与抑制之间的平衡。这些疾病的标志之一是对感觉刺激的超敏性。但是，对其根本原因知之甚少。由于视网膜是中枢神经系统的一部分，它将光转换为神经元信号，因此我们着手研究在产前暴露于丙戊酸（VPA）的青春期小鼠中如何受到影响，丙戊酸是研究ASD内表型的有用工具。怀孕的雌性小鼠在妊娠第11天接受VPA（600 mg / kg，ip）或生理盐水。他们对青春期的雄性幼犬（P29-35）进行了焦虑和社交互动的行为测试。通过免疫测定对已知与ASD相关的蛋白质进行定量和可视化，并通过全视野暗视视网膜电图（ERG）评估视网膜功能。产前暴露于VPA的青春期早期小鼠表现出受损的社会兴趣，并增加了与ASD表型一致的焦虑样行为。GABA，GAD，突触蛋白-1和FMRP蛋白在视网膜中的表达减少，而mGluR5的表达增加。暴露于VPA的a波振幅小于CTR动物，而b波和振荡电位正常。这项研究建立了VPA诱导的ASD模型的青春期雄性小鼠的视网膜功能和蛋白质表达与其他自闭症模型的多个大脑区域中的小鼠相容。这些结果支持这样的观点，即生命早期伴随着兴奋/抑制性失衡的突触障碍与ASD有关，并指向视网膜作为了解其潜在机制的窗口。