Morphometric Analysis of Retinal Ganglion Cell Axons in Normal and Glaucomatous Brown Norway Rats Optic Nerves.

Morphometric Analysis of Retinal Ganglion Cell Axons in Normal and Glaucomatous Brown Norway Rats Optic Nerves.
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正常和青光眼棕色挪威大鼠视神经视网膜神经节细胞轴突的形态测量分析。

DOI:
10.1167/tvst.12.3.8
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发表时间:
2023-03-01
影响因子:
3
通讯作者:
Ethier, C. Ross
Ethier, C. Ross
中科院分区:
医学3区
文献类型:
--
作者:
Goyal, Vidisha;Read, A. Thomas;Brown, Dillon M.;Brawer, Luke;Bateh, Kaitlyn;Hannon, Bailey G.;Feola, Andrew J.;Ethier, C. Ross

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视神经(ON)视网膜神经节细胞(RGC)轴突的参考图谱可以通过检测微妙的RGC轴突变化来促进神经眼科疾病的研究。在这里,我们构建了一个RGC轴突图谱正常血压的眼睛在布朗挪威大鼠,广泛用于青光眼研究,也开发/评估高血压眼轴突损伤的几个新的指标。通过基于深度学习的算法AxoNet2.0处理高血压和血压正常眼的整个ON横截面的光学显微照片,以确定轴突形态学特性,并使用莫里森分级量表(MGS)进行半定量评分,以提供独立于AxoNet2.0结局的损伤评分。为了构建图谱,将ON共形映射到ON“模板”上,并计算每个区域的轴突形态测量数据。我们还开发了基于髓鞘形态测量的损伤指标。在血压正常的眼睛中,平均轴突密度为0.3个轴突/µm2(即,ON中有大约80,000个轴突)。我们测量轴浆直径、偏心率、横截面积、髓鞘比率和厚度。大多数形态学参数表现出广泛的变异系数(CoV),然而,髓鞘厚度CoV只有0.2%,在正常血压的眼睛。在高血压眼中,髓鞘厚度增加与MGS密切相关(P < 0.0001)。我们提出了第一个全面的规范RGC轴突形态测量图谱布朗挪威大鼠的眼睛。我们建议客观的,可重复的损害指标的基础上RGC轴突髓鞘厚度高血压的眼睛。这些工具可以评估RGC的区域变化和使用Brown Norway大鼠的青光眼研究中的整体损伤水平。
A reference atlas of optic nerve (ON) retinal ganglion cell (RGC) axons could facilitate studies of neuro-ophthalmic diseases by detecting subtle RGC axonal changes. Here we construct an RGC axonal atlas for normotensive eyes in Brown Norway rats, widely used in glaucoma research, and also develop/evaluate several novel metrics of axonal damage in hypertensive eyes. Light micrographs of entire ON cross-sections from hypertensive and normotensive eyes were processed through a deep learning-based algorithm, AxoNet2.0, to determine axonal morphological properties and were semiquantitatively scored using the Morrison grading scale (MGS) to provide a damage score independent of AxoNet2.0 outcomes. To construct atlases, ONs were conformally mapped onto an ON “template,” and axonal morphometric data was computed for each region. We also developed damage metrics based on myelin morphometry. In normotensive eyes, average axon density was ∼0.3 axons/µm2 (i.e., ∼80,000 axons in an ON). We measured axoplasm diameter, eccentricity, cross-sectional area, and myelin g-ratio and thickness. Most morphological parameters exhibited a wide range of coefficients of variation (CoV); however, myelin thickness CoV was only ∼2% in normotensive eyes. In hypertensive eyes, increased myelin thickness correlated strongly with MGS (P < 0.0001). We present the first comprehensive normative RGC axon morphometric atlas for Brown Norway rat eyes. We suggest objective, repeatable damage metrics based on RGC axon myelin thickness for hypertensive eyes. These tools can evaluate regional changes in RGCs and overall levels of damage in glaucoma studies using Brown Norway rats.
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DOI: 10.3389/fbioe.2020.00784
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