Table_2_Regional Downregulation of Dopamine Receptor D1 in Bilateral Dorsal Lateral Geniculate Nucleus of Monocular Form-Deprived Amblyopia Models.XLSX

Amblyopia is a common eye disease characterized by impaired best-corrected visual acuity. It starts in early childhood and leads to permanent vision reduction if left untreated. Even though many young patients with amblyopia are well treated in clinical practice, the underlying mechanism remains to be elucidated, which limits not only our understanding of this disease but also the therapeutic approach. To investigate the molecular mechanism of amblyopia, primate and rodent models of monocular-deprived amblyopia were created for mRNA screening and confirmation. We obtained 818 differentially expressed genes from the dorsal lateral geniculate nucleus (dLGN) of a primate model of amblyopia. After Gene Ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, the main enriched pathways were related to neural development. Interestingly, a particular neurotransmitter pathway, the dopaminergic pathway, was identified. The downregulation of dopamine receptor D1 (DRD1) was confirmed in both monkey and mouse samples. Furthermore, the immunofluorescence staining indicated that DRD1 expression was downregulated in both ventrolateral region of the contralateral dLGN and the dorsomedial region of the ipsilateral dLGN in the mouse model. The regions with downregulated expression of DRD1 were the downstream targets of the visual projection from the amblyopic eye. This study suggested that the downregulation of DRD1 in the LGN may be a cause for amblyopia. This may also be a reason for the failure of some clinical cases of levodopa combined with carbidopa applied to amblyopes.

弱视（Amblyopia）是一种以最佳矫正视力受损为特征的常见眼部疾病，始发于幼儿阶段，若未及时治疗则会引发永久性视力减退。尽管临床实践中多数弱视患儿可获得良好的治疗效果，但其潜在发病机制仍有待阐明，这不仅限制了学界对该疾病的认知深度，也制约了治疗策略的开发与优化。为探究弱视的分子致病机制，研究人员构建了单眼剥夺性弱视的灵长类及啮齿类动物模型，用于信使RNA（mRNA）的筛选与验证实验。我们从弱视灵长类动物模型的背外侧膝状体核（dorsal lateral geniculate nucleus，dLGN）中筛选得到818个差异表达基因。经基因本体（Gene Ontology，GO）及京都基因与基因组百科全书（kyoto encyclopedia of genes and genomes，KEGG）富集分析后发现，显著富集的通路主要与神经发育相关。值得关注的是，一条特定的神经递质通路——多巴胺能通路——被成功鉴定。多巴胺受体D1（dopamine receptor D1，DRD1）的表达下调现象在猴及小鼠样本中均得到了验证。进一步的免疫荧光染色实验结果显示，在小鼠弱视模型中，DRD1在对侧背外侧膝状体核的腹外侧区域以及同侧背外侧膝状体核的背内侧区域均呈现表达下调。DRD1表达下调的区域，正是弱视眼视觉投射的下游靶区。本研究表明，背外侧膝状体核内DRD1的表达下调可能是弱视的致病诱因之一，这也或许可以解释部分临床病例中，左旋多巴联合卡比多巴治疗弱视患者收效不佳的原因。