Liu Ying V, Sodhi Simrat K, Xue Gilbert, Teng Derek, Agakishiev Dzhalal, McNally Minda M, Harris-Bookman Sarah, McBride Caitlin, Konar Gregory J, Singh Mandeep S
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, USA.
Transl Vis Sci Technol. 2020 Jun 3;9(7):5. doi: 10.1167/tvst.9.7.5. eCollection 2020 Jun.
Short-term improvements in retinal anatomy are known to occur in preclinical models of photoreceptor transplantation. However, correlative changes over the long term are poorly understood. We aimed to develop a quantifiable imaging biomarker grading scheme, using noninvasive multimodal confocal scanning laser ophthalmoscopy (cSLO) imaging, to enable serial evaluation of photoreceptor transplantation over the long term.
Photoreceptor cell suspensions or sheets from rhodopsin-green fluorescent protein mice were transplanted subretinally, into either or mice. Multimodal cSLO imaging was performed serially for up to three months after transplantation. Imaging biomarkers were scored, and a grade was defined for each eye by integrating the scores. Image grades were correlated with immunohistochemistry (IHC) data.
Multimodal imaging enabled the extraction of quantitative imaging biomarkers including graft size, GFP intensity, graft length, on-target graft placement, intra-graft lamination, hemorrhage, retinal atrophy, and periretinal proliferation. Migration of transplanted material was observed. Changes in biomarker scores and grades were detected in 14/16 and 7/16 eyes, respectively. A high correlation was found between image grades and IHC parameters.
Serial evaluation of multiple imaging biomarkers, when integrated into a per-eye grading scheme, enabled comprehensive tracking of longitudinal changes in photoreceptor cell grafts over time. The application of systematic multimodal in vivo imaging could be useful in increasing the efficiency of preclinical retinal cell transplantation studies in rodents and other animal models.
By allowing longitudinal evaluation of the same animal over time, and providing quantifiable biomarkers, non-invasive multimodal imaging improves the efficiency of retinal transplantation studies in animal models. Such assays will facilitate the development of cell therapy for retinal diseases.
已知在光感受器移植的临床前模型中视网膜解剖结构会出现短期改善。然而，长期的相关变化却知之甚少。我们旨在开发一种可量化的成像生物标志物分级方案，使用非侵入性多模态共聚焦扫描激光检眼镜（cSLO）成像，以便能够长期对光感受器移植进行系列评估。
将来自视紫红质 - 绿色荧光蛋白小鼠的光感受器细胞悬液或薄片视网膜下移植到野生型或免疫缺陷小鼠体内。移植后连续三个月进行多模态cSLO成像。对成像生物标志物进行评分，并通过整合分数为每只眼睛定义一个等级。图像等级与免疫组织化学（IHC）数据相关。
多模态成像能够提取包括移植物大小、绿色荧光蛋白强度、移植物长度、靶向移植物放置、移植物内分层、出血、视网膜萎缩和视网膜周增殖等定量成像生物标志物。观察到移植材料的迁移。分别在14/16只和7/16只眼中检测到生物标志物分数和等级的变化。发现图像等级与IHC参数之间存在高度相关性。
当将多个成像生物标志物的系列评估整合到每只眼睛的分级方案中时，能够全面跟踪光感受器细胞移植物随时间的纵向变化。系统性多模态体内成像的应用可能有助于提高啮齿动物和其他动物模型中临床前视网膜细胞移植研究的效率。
通过允许对同一动物进行长期评估，并提供可量化的生物标志物，非侵入性多模态成像提高了动物模型中视网膜移植研究的效率。此类检测将促进视网膜疾病细胞治疗的发展。
