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闭合性眼球损伤小鼠模型中的神经视网膜细胞死亡:病理和功能特征。

Neuroretinal cell death in a murine model of closed globe injury: pathological and functional characterization.

机构信息

Neurotrauma and Neurodegeneration Section, Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom.

出版信息

Invest Ophthalmol Vis Sci. 2012 Oct 17;53(11):7220-6. doi: 10.1167/iovs.12-9887.

DOI:10.1167/iovs.12-9887
PMID:22977137
Abstract

PURPOSE

Blunt ocular trauma causes severe retinal injury with death of neuroretinal tissue, scarring, and permanent visual loss. The mechanisms of cell death are not known, and there are no therapeutic interventions that improve visual outcome. We aimed to study the extent, distribution, and functional consequences of cell death by developing and characterizing a rat model of retinal injury caused by blunt ocular trauma.

METHODS

The eyes of anesthetized adult rats were injured by either weight drop or low-velocity ballistic trauma and assessed by clinical examination, electroretinography, light microscopy, electron microscopy, and TUNEL. Projectile velocity was measured and standardized.

RESULTS

Weight drop did not cause reproducible retinal injury, and the energy threshold for retinal injury was similar to that for rupture. Low-velocity ballistic trauma to the inferior sclera created a reproducible retinal injury, with central sclopetaria retinae, retinal necrosis, and surrounding commotio retinae with specific photoreceptor cell death and sparing of cells in the other retinal layers. The extent of photoreceptor cell death declined and necrosis progressed to apoptosis with increasing distance from the impact site.

CONCLUSIONS

This is the only murine model of closed globe injury and the only model of retinal trauma with specific photoreceptor cell death. The clinical appearance mirrors that in severe retinal injury after blunt ocular trauma in humans, and the ultrastructural features are consistent with human and animal studies of commotio retinae. After ocular trauma, photoreceptor apoptosis may be prevented and visual outcomes improved by blocking of the cell death pathways.

摘要

目的

钝挫伤可导致严重的视网膜损伤,引起神经视网膜组织死亡、瘢痕形成和永久性视力丧失。目前尚不清楚细胞死亡的机制,也没有任何治疗干预措施可以改善视力预后。我们旨在通过建立和描述一种由钝挫伤引起的大鼠视网膜损伤模型来研究细胞死亡的程度、分布和功能后果。

方法

通过对麻醉成年大鼠的眼睛进行重物跌落或低速度弹道创伤,并通过临床检查、视网膜电图、光镜、电镜和 TUNEL 进行评估。测量并标准化了弹丸速度。

结果

重物跌落未引起可重复的视网膜损伤,视网膜损伤的能量阈值与破裂相似。对下巩膜进行低速度弹道创伤可造成可重复的视网膜损伤,伴有中央巩膜视网膜撕裂、视网膜坏死以及周围的挫伤视网膜,伴有特定的光感受器细胞死亡和其他视网膜层细胞的保留。随着距撞击部位的距离增加,光感受器细胞死亡的程度下降,坏死进展为细胞凋亡。

结论

这是唯一的闭合性眼球损伤的小鼠模型,也是唯一具有特定光感受器细胞死亡的视网膜创伤模型。临床外观与人类钝挫伤后严重视网膜损伤相似,超微结构特征与人类和动物的挫伤视网膜研究一致。在眼外伤后,通过阻断细胞死亡途径,可能预防光感受器细胞凋亡并改善视力预后。

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