Wilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Department of Ophthalmology, University Hospital Heidelberg, Heidelberg, Germany.
Br J Ophthalmol. 2024 Feb 21;108(3):343-348. doi: 10.1136/bjo-2022-322180.
Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (), which localises to Bowman's layer (BL), is thought to function in stress-bearing areas, such as BL. Given the putative protective role of in biomechanical stability, this study aims to characterise expression in all corneal layers involved in KC.
TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally, was knocked out in vitro in immortalised HEK293 cells.
expression was reduced at transcript levels in KC epithelium compared with controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane and stroma.
The apparent absence of COL12A1 in KC BL, together with the functional importance that is thought to have in stress bearing areas, suggests that may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead to dysregulation in KC.
角膜生物力学衰竭是圆锥角膜(KC)的标志;然而,这种衰竭的原因仍难以捉摸。胶原 XII 型(),定位于 Bowman 层(BL),被认为在应力承受区域(如 BL)发挥作用。鉴于在生物力学稳定性中具有假定的保护作用,本研究旨在描述 KC 相关角膜各层中表达的情况。
对 31 例进行性 KC 和近视对照眼的角膜上皮样本进行 TaqMan 定量 PCR。使用 61 例角膜移植术中的全层 KC 病例和 18 例非 KC 尸检眼的全层角膜构建组织微阵列,并使用针对 COL12A1 的抗体进行染色。此外,在永生化 HEK293 细胞中体外敲除。
与对照组相比,KC 上皮中的表达在转录水平上降低(比值:0.58,p<0.03)。免疫组织化学研究表明,BL 中的 COL12A1 蛋白表达无法检测到,KC 上皮、基底膜和基质中的表达减少。
KC BL 中明显缺乏 COL12A1,加上 被认为在应力承受区域具有重要功能,表明可能在 KC 的发病机制中发挥作用。需要进一步研究以探讨导致 KC 中失调的机制。