Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Optegra Eye Health Care Clinic in Poznan, Poznan, Poland.
Front Immunol. 2023 Jul 6;14:1197054. doi: 10.3389/fimmu.2023.1197054. eCollection 2023.
Keratoconus (KTCN) is the most common corneal ectasia resulting in a conical shape of the cornea. Here, genomic variation in the corneal epithelium (CE) across the keratoconic cone surface in patients with KTCN and its relevance in the functioning of the immune system were assessed.
Samples from four unrelated adolescent patients with KTCN and two control individuals were obtained during the CXL and PRK procedures, respectively. Three regions, , and , were separated towards the whole-genome sequencing (WGS) study embracing a total of 18 experimental samples. The coding and non-coding sequence variation, including structural variation, was assessed and then evaluated together with the previously reported transcriptomic outcomes for the same CE samples and full-thickness corneas.
First, pathway enrichment analysis of genes with identified coding variants pointed to "Antigen presentation" and "Interferon alpha/beta signaling" as the most overrepresented pathways, indicating the involvement of inflammatory responses in KTCN. Both coding and non-coding sequence variants were found in genes (or in their close proximity) linked to the previously revealed KTCN-specific cellular components, namely, "Actin cytoskeleton", "Extracellular matrix", "Collagen-containing extracellular matrix", "Focal adhesion", "Hippo signaling pathway", and "Wnt signaling" pathways. No genomic heterogeneity across the corneal surface was found comparing the assessed regions. Thirty-five chromosomal regions enriched in both coding and non-coding KTCN-specific sequence variants were revealed, with a most representative 5q locus previously recognized as involved in KTCN.
The identified genomic features indicate the involvement of innate and adaptive immune system responses in KTCN pathogenesis.
圆锥角膜（KTCN）是最常见的角膜扩张症，导致角膜呈圆锥形。在这里，评估了 KTCN 患者角膜上皮（CE）在圆锥角膜表面的基因组变异及其与免疫系统功能的相关性。
在 CXL 和 PRK 手术期间分别从四个无关的青少年 KTCN 患者和两个对照个体中获得样本。将三个区域、和 分离出来进行全基因组测序（WGS）研究，共包含 18 个实验样本。评估了编码和非编码序列变异，包括结构变异，然后与相同 CE 样本和全厚角膜的先前报道的转录组结果一起评估。
首先，对鉴定出的编码变异基因的途径富集分析表明，“抗原呈递”和“干扰素 α/β 信号”是最具代表性的途径，表明炎症反应参与了 KTCN。编码和非编码序列变异都存在于与先前揭示的 KTCN 特异性细胞成分相关的基因（或其附近）中，即“肌动蛋白细胞骨架”、“细胞外基质”、“含胶原的细胞外基质”、“黏附斑”、“Hippo 信号通路”和“Wnt 信号通路”途径。在评估的三个区域之间，没有发现角膜表面的基因组异质性。发现了 35 个富含编码和非编码 KTCN 特异性序列变异的染色体区域，其中最具代表性的 5q 基因座先前被认为与 KTCN 有关。
所鉴定的基因组特征表明先天和适应性免疫系统反应参与了 KTCN 的发病机制。
