Assessment and in vivo scoring of murine experimental autoimmune uveoretinitis using optical coherence tomography.

Assessment and in vivo scoring of murine experimental autoimmune uveoretinitis using optical coherence tomography.
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DOI:
10.1371/journal.pone.0063002
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Luhmann UF
Luhmann UF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chu CJ;Herrmann P;Carvalho LS;Liyanage SE;Bainbridge JW;Ali RR;Dick AD;Luhmann UF

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尽管在临床影像学和分级方面取得了进展,但我们对实验性自身免疫性葡萄膜视网膜炎(EAU)的视网膜免疫反应及其形态学相关性的理解一直受到尸检组织学要求的阻碍。迄今为止,监测EAU疾病进展期间发生的变化并实时评估治疗干预的效果尚不可能。我们想确定光学相干断层扫描(OCT)是否可以检测炎症期间的视网膜内变化,并确定其作为准确评分EAU的工具的实用性。分别于15、26、36、60 d对C57BL/6J小鼠和动物进行EAU诱导。在每个时间点,同时进行光谱- oct扫描、局部内窥镜眼底成像(TEFI)、眼底荧光素血管造影(FFA)和cd45免疫标记组织学检查。利用免疫组织化学和3D重建技术进一步表征视网膜平板支架的OCT特征。OCT检查视盘肿胀、玻璃体混浊,组织学上与CD45+细胞浸润一致。FFA和OCT鉴定的血管炎与血管周围骨髓和t细胞浸润相匹配,可以与未受影响的血管区分开来。随着时间的推移,这些变化的演变可以在同一只眼睛中被跟踪。视网膜褶皱可见,被发现包裹着活化的骨髓细胞、t细胞和小胶质细胞的混合群体。利用这些特征,开发了基于oct的EAU评分系统,该评分系统与经验证的组织学评分系统(Pearson r2 = 0.6392, P<0.0001, n = 31眼)和基于TEFI的评分系统(r2 = 0.6784, P<0.0001)具有显著相关性。OCT区分小鼠EAU在体内的基本特征,允许对肠道内变化进行动态评估,并可用于疾病严重程度评分。因此,它允许组织与随后的细胞和功能评估同步,并提高动物使用效率。通过将OCT信号与EAU的免疫组织化学联系起来,我们的发现为解释人类葡萄膜炎的OCT变化提供了机会。
Despite advances in clinical imaging and grading our understanding of retinal immune responses and their morphological correlates in experimental autoimmune uveoretinitis (EAU), has been hindered by the requirement for post-mortem histology. To date, monitoring changes occurring during EAU disease progression and evaluating the effect of therapeutic intervention in real time has not been possible. We wanted to establish whether optical coherence tomography (OCT) could detect intraretinal changes during inflammation and to determine its utility as a tool for accurate scoring of EAU. EAU was induced in C57BL/6J mice and animals evaluated after 15, 26, 36 and 60 days. At each time-point, contemporaneous Spectralis-OCT scanning, topical endoscopic fundal imaging (TEFI), fundus fluorescein angiography (FFA) and CD45-immunolabelled histology were performed. OCT features were further characterised on retinal flat-mounts using immunohistochemistry and 3D reconstruction. Optic disc swelling and vitreous opacities detected by OCT corresponded to CD45+ cell infiltration on histology. Vasculitis identified by FFA and OCT matched perivascular myeloid and T-cell infiltrates and could be differentiated from unaffected vessels. Evolution of these changes could be followed over time in the same eye. Retinal folds were visible and found to encapsulate mixed populations of activated myeloid cells, T-cells and microglia. Using these features, an OCT-based EAU scoring system was developed, with significant correlation to validated histological (Pearson r2 = 0.6392, P<0.0001, n = 31 eyes) and TEFI based scoring systems (r2 = 0.6784, P<0.0001). OCT distinguishes the fundamental features of murine EAU in vivo, permits dynamic assessment of intraretinal changes and can be used to score disease severity. As a result, it allows tissue synchronisation with subsequent cellular and functional assessment and greater efficiency of animal usage. By relating OCT signals with immunohistochemistry in EAU, our findings offer the opportunity to inform the interpretation of OCT changes in human uveitis.
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发表时间: 2012
期刊: PloS one
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作者:
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