Retinal detachment (RD) results in disruption of retinal physiology and visual function. Although surgical intervention has been well-developed to restore the retinal anatomic structure, post-op progression of visual function decline is prominent in a large proportion of patients. Therefore, the establishment of a disease model that accurately mimics RD pathogenesis is crucial to mechanistic study and drug screening. General protocols to induce RD in mice are frequently associated with complications leading to model instability and reduced reproducibility. In this study, we established a stable and reproducible mice RD model with a detached area of over 90% and rare complications. Briefly, the modified method was realized by vitreous humor extraction to reduce intraocular pressure, followed by directly-visible hyaluronic acid injection into subretinal space. The detachment of retina was confirmed by fundus photography, and progressive thinning of the outer nuclear layer (ONL) was determined by HE staining. Apoptotic signals were prominent in the ONL. Consistently, visual function was significantly compromised as determined by ERG. Moreover, retinal vasculature appeared to remodel and acquired winding, twisted and dilated structures illustrated by 3D reconstruction. In addition, activation of Müller cells and microglia, and infiltration of blood-derived macrophages were detected locally. Collectively, we have established a modified protocol to model RD with increased stability, reproducibility and fewer complications, and 3D high-resolution imaging and reconstruction of vasculature could provide new tools to evaluate this model.

中文翻译：

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一种改进的建立小鼠视网膜脱离模型的方法及其3D血管评估。

视网膜脱离（RD）导致视网膜生理和视觉功能的破坏。尽管为恢复视网膜解剖结构已进行了广泛的外科手术，但术后手术后视觉功能下降的进展在大部分患者中尤为突出。因此，建立能够精确模拟RD发病机理的疾病模型对于机理研究和药物筛选至关重要。在小鼠中诱导RD的一般方案通常与导致模型不稳定和降低可重复性的并发症相关。在这项研究中，我们建立了一个稳定且可重现的小鼠RD模型，其分离面积超过90％，并发症很少。简而言之，改良方法是通过玻璃体液提取来降低眼内压，然后将透明质酸注射入视网膜下腔。通过眼底照相术确认视网膜的脱离，并通过HE染色确定外核层（ONL）的逐渐变薄。凋亡信号在ONL中突出。一致地，如ERG所确定，视觉功能显着受损。此外，视网膜脉管系统似乎可以重塑并获得缠绕，扭曲和扩张的结构，如3D重建所示。此外，还可以局部检测到Müller细胞和小胶质细胞的活化，以及源自血液的巨噬细胞的浸润。总的来说，我们已经建立了经过改进的协议来对RD进行建模，从而提高了稳定性，可重复性并且减少了并发症，