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探索激光诱导的急性和慢性视网膜静脉闭塞小鼠模型:发展、体内实时成像及应用前景。

Exploring laser-induced acute and chronic retinal vein occlusion mouse models: Development, temporal in vivo imaging, and application perspectives.

机构信息

Department of Ophthalmology and Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

PLoS One. 2024 Jun 17;19(6):e0305741. doi: 10.1371/journal.pone.0305741. eCollection 2024.

Abstract

Photodynamic venous occlusion is a commonly accepted method for establishing mouse models of retinal vein occlusion (RVO). However, existing model parameters do not distinguish between acute and chronic RVO subtypes. Large variations in laser energy seem to correlate with fluctuating retinopathy severity and high rates of venous recanalization during the acute phase, along with the variable levels of retinal perfusion during the chronic phase. After optimizing the modeling procedure and defining success and exclusion criteria, laser energy groups of 80mW, 100mW, and 120mW were established. Multimodal imaging confirmed that higher energy levels increased the incidence of retinal cystoid edema and intraretinal hemorrhage, exacerbated the severity of exudative retinal detachment, and reduced the venous recanalization rate. For the acute model, 100mW was considered an appropriate parameter for balancing moderate retinopathy and venous recanalization. Continuous imaging follow-up revealed that day 1 after RVO was the optimal observation point for peaking of retinal thickness and intensive occurrence of retinal cystic edema and intraretinal hemorrhage. After excluding the influence of venous recanalization on retinal thickness, acute retinal edema demonstrated a positive response to standard anti-vascular endothelial growth factor therapy, validating the clinical relevance of the acute RVO model for further study in pathogenic mechanisms and therapeutic efficacy. For the chronic model, the 120mW parameter with the lowest venous recanalization rate was applied, accompanied by an increase in both photocoagulation shots and range to ensure sustained vein occlusion. Imaging follow-up clarified non-ischemic retinopathy characterized by tortuosity and dilation of the distal end, branches, and adjacent veins of the occluded vein. These morphological changes are quantifiable and could be combined with electrophysiological functional assessment for treatment effectiveness evaluation. Moreover, the stable state of venous occlusion may facilitate investigations into response and compensation mechanisms under conditions of chronic retinal hypoperfusion.

摘要

光动力静脉闭塞是建立视网膜静脉闭塞(RVO)小鼠模型的常用方法。然而,现有的模型参数不能区分急性和慢性 RVO 亚型。激光能量的较大变化似乎与视网膜病变严重程度的波动和急性阶段静脉再通率高以及慢性阶段视网膜灌注水平的变化有关。在优化建模程序并定义成功和排除标准后,建立了 80mW、100mW 和 120mW 的激光能量组。多模态成像证实,较高的能量水平增加了视网膜囊样水肿和视网膜内出血的发生率,加重了渗出性视网膜脱离的严重程度,并降低了静脉再通率。对于急性模型,100mW 被认为是平衡中度视网膜病变和静脉再通的合适参数。连续成像随访显示,RVO 后第 1 天是观察视网膜厚度峰值和密集发生视网膜囊样水肿和视网膜内出血的最佳观察点。在排除静脉再通对视网膜厚度的影响后,急性视网膜水肿对标准抗血管内皮生长因子治疗有积极反应,验证了急性 RVO 模型在发病机制和治疗效果研究中的临床相关性。对于慢性模型,应用了静脉再通率最低的 120mW 参数,并增加了光凝次数和范围,以确保持续的静脉闭塞。成像随访明确了非缺血性视网膜病变的特征,表现为闭塞静脉的末端、分支和相邻静脉的迂曲和扩张。这些形态变化是可量化的,可以与电生理功能评估相结合,用于治疗效果评估。此外,静脉闭塞的稳定状态可能有助于研究慢性视网膜低灌注下的反应和代偿机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6162/11182531/8f7238a8dc0d/pone.0305741.g001.jpg

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