Manik Bansal, Bingrui Wang, Susannah Waxman, Fuqiang Zhong, Yi Hua, Yuankai Lu, Juan Reynaud, Brad Fortune, Ian A Sigal
{"title":"Proposing a Methodology for Axon-Centric Analysis of IOP-Induced Mechanical Insult.","authors":"Manik Bansal, Bingrui Wang, Susannah Waxman, Fuqiang Zhong, Yi Hua, Yuankai Lu, Juan Reynaud, Brad Fortune, Ian A Sigal","doi":"10.1167/iovs.65.13.1","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>IOP-induced mechanical insult on retinal ganglion cell axons within the optic nerve head (ONH) is believed to be a key factor in axonal damage and glaucoma. However, most studies focus on tissue-level mechanical deformations, overlooking that axons are long and thin, and that their susceptibility to damage likely depends on the insult's type (e.g. stretch/compression) and orientation (longitudinal/transverse). We propose an axon-centric approach to quantify IOP-induced mechanical insult from an axon perspective.</p><p><strong>Methods: </strong>We used optical coherence tomography (OCT) scans from a healthy monkey eye along with histological images of cryosections to reconstruct the axon-occupied volume including detailed lamina cribrosa (LC) pores. Tissue-level strains were determined experimentally using digital volume correlation from OCT scans at baseline and elevated IOPs, then transformed into axonal strains using axon paths estimated by a fluid mechanics simulation.</p><p><strong>Results: </strong>Axons in the LC and post-LC regions predominantly experienced longitudinal compression and transverse stretch, whereas those in the pre-LC and ONH rim mainly suffered longitudinal stretch and transverse compression. No clear patterns were observed for tissue-level strains.</p><p><strong>Conclusions: </strong>Our approach allowed discerning axonal longitudinal and transverse mechanical insults, which are likely associated with different mechanisms of axonal damage. The technique also enabled quantifying insult along individual axon paths, providing a novel link relating the retinal nerve fiber layer and the optic nerve through the LC via individual axons. This is a promising approach to establish a clearer connection between IOP-induced insult and glaucoma. Further studies should evaluate a larger cohort.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Investigative ophthalmology & visual science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1167/iovs.65.13.1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: IOP-induced mechanical insult on retinal ganglion cell axons within the optic nerve head (ONH) is believed to be a key factor in axonal damage and glaucoma. However, most studies focus on tissue-level mechanical deformations, overlooking that axons are long and thin, and that their susceptibility to damage likely depends on the insult's type (e.g. stretch/compression) and orientation (longitudinal/transverse). We propose an axon-centric approach to quantify IOP-induced mechanical insult from an axon perspective.
Methods: We used optical coherence tomography (OCT) scans from a healthy monkey eye along with histological images of cryosections to reconstruct the axon-occupied volume including detailed lamina cribrosa (LC) pores. Tissue-level strains were determined experimentally using digital volume correlation from OCT scans at baseline and elevated IOPs, then transformed into axonal strains using axon paths estimated by a fluid mechanics simulation.
Results: Axons in the LC and post-LC regions predominantly experienced longitudinal compression and transverse stretch, whereas those in the pre-LC and ONH rim mainly suffered longitudinal stretch and transverse compression. No clear patterns were observed for tissue-level strains.
Conclusions: Our approach allowed discerning axonal longitudinal and transverse mechanical insults, which are likely associated with different mechanisms of axonal damage. The technique also enabled quantifying insult along individual axon paths, providing a novel link relating the retinal nerve fiber layer and the optic nerve through the LC via individual axons. This is a promising approach to establish a clearer connection between IOP-induced insult and glaucoma. Further studies should evaluate a larger cohort.
目的:眼压对视神经头(ONH)内视网膜神经节细胞轴突造成的机械损伤被认为是轴突损伤和青光眼的关键因素。然而,大多数研究都侧重于组织层面的机械变形,忽略了轴突又长又细,而且它们对损伤的敏感性可能取决于损伤的类型(如拉伸/压缩)和方向(纵向/横向)。我们提出了一种以轴突为中心的方法,从轴突的角度量化眼压诱导的机械损伤:方法:我们使用健康猴眼的光学相干断层扫描(OCT)和冷冻切片的组织学图像来重建轴突占据的体积,包括详细的颅底薄层(LC)孔隙。组织级应变是通过基线和眼压升高时的 OCT 扫描数字体积相关性实验确定的,然后通过流体力学模拟估算的轴突路径转化为轴突应变:LC和LC后区域的轴突主要受到纵向压缩和横向拉伸,而LC前和ONH边缘的轴突主要受到纵向拉伸和横向压缩。组织层面的应变没有观察到明显的模式:我们的方法可以分辨轴突的纵向和横向机械损伤,这可能与轴突损伤的不同机制有关。该技术还能量化单个轴突路径上的损伤,通过单个轴突将视网膜神经纤维层和视神经通过视网膜神经纤维层联系起来。这是一种很有前景的方法,可以更清晰地建立眼压诱导的损伤与青光眼之间的联系。进一步的研究应该对更大的群体进行评估。
期刊介绍:
Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.