A retinal model of cerebral malaria
A retinal model of cerebral malaria
复制标题
DOI：
10.1038/s41598-019-39143-z
复制
发表时间：
2019-03-05
影响因子：
4.6
通讯作者：
Seeliger, Mathias W.
中科院分区：
文献类型：
--
作者：
Paquet-Durand, Francois;Beck, Susanne C.;Seeliger, Mathias W.
疟疾是全世界每年约50万人死亡的致病因素。脑型疟疾是这种疾病的一种特别严重的并发症，因此与极高的死亡率有关。疟疾视网膜病变是一种眼部表现，通常与脑型疟疾有关，并且可能与其病理生理学有很大的共同之处。在这里，我们描述了鼠疟疾视网膜病变复制相应的人类疾病的主要标志。在活体动物中，我们能够通过非侵入性体内视网膜成像跟踪用GFP转基因标记的疟原虫的循环和细胞定位。我们发现疟疾寄生虫穿过血视网膜屏障并浸润神经视网膜，伴随着广泛的、不可逆的和持久的视网膜神经变性。此外，用双氢青蒿素进行抗疟疾治疗，大大减少了循环寄生虫的负荷，但仅部分解决了视网膜病变的症状。总之，我们在这里介绍了一种新的临床前模型，为人类脑型疟疾，是更直接地进入疾病的病理生理学研究和新的治疗方法的发展。此外，体内视网膜成像可用作人类疾病的早期诊断的有价值的工具。
Malaria is a causative factor in about 500.000 deaths each year world-wide. Cerebral malaria is a particularly severe complication of this disease and thus associated with an exceedingly high mortality. Malaria retinopathy is an ocular manifestation often associated with cerebral malaria, and presumably shares a substantial part of its pathophysiology. Here, we describe that indeed murine malaria retinopathy reproduced the main hallmarks of the corresponding human disease. In the living animal, we were able to follow the circulation and cellular localization of malaria parasites transgenically labelled with GFP via non-invasive in vivo retinal imaging. We found that malaria parasites cross the blood-retinal-barrier and infiltrate the neuroretina, concomitant with an extensive, irreversible, and long-lasting retinal neurodegeneration. Furthermore, anti-malarial treatment with dihydroartemisinin strongly diminished the load of circulating parasites but resolved the symptoms of the retinopathy only in part. In summary, we introduce here a novel preclinical model for human cerebral malaria that is much more directly accessible for studies into disease pathophysiology and development of novel treatment approaches. In vivo retinal imaging may furthermore serve as a valuable tool for the early diagnosis of the human disease.