School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Transl Vis Sci Technol. 2023 Mar 1;12(3):8. doi: 10.1167/tvst.12.3.8.
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.
视神经（ON）视网膜神经节细胞（RGC）轴突参考图谱可以通过检测细微的 RGC 轴突变化来促进神经眼科疾病的研究。在这里，我们构建了布朗挪威大鼠正常眼压眼的 RGC 轴突图谱，该大鼠广泛用于青光眼研究，并且还开发/评估了高血压眼轴突损伤的几种新指标。
使用基于深度学习的算法 AxoNet2.0 处理来自高血压和正常眼压眼的整个 ON 横截面的光镜照片，以确定轴突形态特征，并使用 Morrison 分级量表（MGS）对其进行半定量评分，以提供独立于 AxoNet2.0 结果的损伤评分。为了构建图谱，将 ON 进行共形映射到 ON“模板”上，并为每个区域计算轴突形态计量数据。我们还开发了基于髓鞘形态计量学的损伤指标。
在正常眼压眼中，平均轴突密度约为 0.3 个轴突/µm2（即 ON 中有约 80,000 个轴突）。我们测量了轴浆直径、偏心度、横截面积和髓鞘 g-比值和厚度。大多数形态参数表现出广泛的变异系数（CoV）；然而，正常眼压眼中的髓鞘厚度 CoV 仅约为 2%。在高血压眼中，髓鞘厚度的增加与 MGS 密切相关（P < 0.0001）。
我们首次为布朗挪威大鼠眼睛提供了全面的正常 RGC 轴突形态计量学图谱。我们建议使用高血压眼的 RGC 轴突髓鞘厚度作为客观、可重复的损伤指标。
汪竹
