Mozzer Ann, Raj Joe Gerald Jesu, Yasmin Nushrat, Esposito Edward, Pitha Ian
Department of Ophthalmology, Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Moran Eye Center, University of Utah, Salt Lake City, UT, 84132, USA.
Sci Rep. 2025 Jul 1;15(1):21207. doi: 10.1038/s41598-025-08251-4.
These studies aimed to study the mechanisms of glaucomatous peripapillary scleral (PPS) remodeling by investigating IOP-induced changes in fibroblast actin-collagen alignment and nuclear morphology in mouse PPS. Cryosections from the optic nerve heads (ONH) of eyes isolated 1- and 6-weeks after bead-induced IOP elevation were imaged for nuclei, fibrillar actin (FA), and collagen (second harmonic generation, SHG). Two-dimensional nuclear morphology was analyzed using VAMPIRE machine-learning image analysis and FA-collagen alignment was determined by comparing vector fields of FA and SHG images. Nuclear morphology was regionally defined with the internal (pial) PPS (iPPS) containing nuclei with higher aspect ratios than the peripheral PPS (outer PPS, oPPS) and peripheral sclera. FA-collagen alignment was higher in the PPS than in the peripheral sclera (7.1 ± 2.5° versus 10.0 ± 1.4°, p = 0.05, n = 6). One and six weeks after BI, there were non-significant nuclear morphologic changes reflecting a transition to a rounder shape in all scleral regions and persistently reduced FA-collagen alignment in the PPS regions. This study therefore concludes that chronic IOP elevation is associated with persistent alterations in FA-collagen alignment that indicate sustained cellular responses to tissue stress.
这些研究旨在通过研究眼压升高引起的小鼠视乳头周围巩膜（PPS）成纤维细胞肌动蛋白-胶原蛋白排列和核形态变化，来探讨青光眼性PPS重塑的机制。对在珠子诱导眼压升高后1周和6周分离的眼球视神经乳头（ONH）的冰冻切片进行成像，以观察细胞核、纤维状肌动蛋白（FA）和胶原蛋白（二次谐波产生，SHG）。使用VAMPIRE机器学习图像分析来分析二维核形态，并通过比较FA和SHG图像的矢量场来确定FA-胶原蛋白排列。核形态在区域上被定义为内部（软膜）PPS（iPPS），其细胞核的纵横比比周边PPS（外部PPS，oPPS）和周边巩膜更高。PPS中FA-胶原蛋白排列高于周边巩膜（7.1±2.5°对10.0±1.4°，p = 0.05，n = 6）。在珠子诱导眼压升高后1周和6周，所有巩膜区域均出现反映向更圆形状转变的无显著核形态变化，且PPS区域的FA-胶原蛋白排列持续降低。因此，本研究得出结论，慢性眼压升高与FA-胶原蛋白排列的持续改变有关，这表明细胞对组织应激的持续反应。
