Pyatla Goutham, Bera Samir, Mishra Ashish, Mandal Anil K, Chakrabarti Subhabrata
Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L V Prasad Eye Institute, Hyderabad, Telangana, India.
Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Semin Ophthalmol. 2025 Nov;40(8):733-742. doi: 10.1080/08820538.2024.2435944. Epub 2024 Dec 9.
The anterior segment of the eye plays a crucial role in maintaining the normal intraocular pressure and vision. Developmental defects in the anterior segment structures lead to anterior segment dysgenesis (ASD) and primary congenital glaucoma (PCG), which share overlapping clinical features. Several genes have been mapped and characterized in ASD, some of which are also involved in other glaucoma phenotypes. PCG exhibits genetic heterogeneity like ASD, but the known genes do not account for the entire genetic basis of the disease. Considering the significant phenotypic and genotypic overlap between ASD and PCG, this article explores the possible involvements of ASD-associated genes in PCG pathogenesis.
A nonsystematic search in PubMed was performed using various combinations of keywords related to ASD, glaucoma, genetics, and molecular mechanisms, and articles published up until March 2024 were considered. Specifically, information pertaining to ASD-associated genes (, and ) was extracted, and their expressions were determined from the GTEx and EMBL-EBI Expression Atlas. Interactions of these genes were determined through the Ingenuity Pathway Analysis software.
Most of the ASD-associated genes were found to be highly expressed in the early embryonic stages. Interactome analysis revealed that , and interacted through the NFκB and Akt/PI3K pathways, either directly, or through interactions with other partners. , and interacted through Wnt and Hedgehog signaling pathways. Both ASD and PCG present similar clinical features and harbor mutations in genes that are implicated in both these conditions. Collectively, we constructed a hypothetical model and proposed two parallel mechanisms comprising the defects in the anterior chamber angle and cell death in PCG pathogenesis.
Our findings suggest that complex interplay of these ASD-associated genes and their interactions could potentially result in defects in the anterior chamber angle and trabecular meshwork and induce cell death, resulting in PCG pathogenesis.
眼前节在维持正常眼压和视力方面起着至关重要的作用。眼前节结构的发育缺陷会导致眼前节发育异常（ASD）和原发性先天性青光眼（PCG），这两种疾病具有重叠的临床特征。已有多个基因在ASD中被定位和表征，其中一些基因也与其他青光眼表型有关。PCG与ASD一样表现出遗传异质性，但已知基因并不能解释该疾病的全部遗传基础。考虑到ASD和PCG之间显著的表型和基因型重叠，本文探讨了ASD相关基因在PCG发病机制中的可能作用。
在PubMed中进行非系统性检索，使用与ASD、青光眼、遗传学和分子机制相关的各种关键词组合，并纳入截至2024年3月发表的文章。具体而言，提取与ASD相关基因（ 、 和 ）的信息，并从GTEx和EMBL-EBI表达图谱中确定它们的表达情况。通过Ingenuity Pathway Analysis软件确定这些基因的相互作用。
发现大多数ASD相关基因在胚胎早期高度表达。相互作用组分析显示， 、 和 直接或通过与其他伙伴的相互作用，通过NFκB和Akt/PI3K途径相互作用。 、 和 通过Wnt和Hedgehog信号通路相互作用。ASD和PCG都呈现相似的临床特征，并且在与这两种疾病都相关的基因中存在突变。总体而言，我们构建了一个假设模型，并提出了两种平行机制，包括前房角缺陷和PCG发病机制中的细胞死亡。
我们的研究结果表明，这些ASD相关基因的复杂相互作用及其相互作用可能会导致前房角和小梁网缺陷，并诱导细胞死亡，从而导致PCG发病。
