Matsumoto Hidetaka, Mukai Ryo, Hoshino Junki, Oda Mai, Matsuzaki Toshiyuki, Ishizaki Yasuki, Shibasaki Koji, Akiyama Hideo
Department of Ophthalmology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, Japan.
PLoS One. 2021 Jan 28;16(1):e0246115. doi: 10.1371/journal.pone.0246115. eCollection 2021.
Pachychoroid spectrum diseases have been described as a new clinical entity within the spectrum of macular disorders. "Pachychoroid" is defined as choroidal thickening associated with dilated outer choroidal vessels often showing retinal pigment epithelium (RPE) degeneration. Although various clinical studies on the pachychoroid spectrum diseases have been conducted, the pathophysiology of pachychoroid has yet to be fully elucidated. In this study, we attempted to establish a mouse model of pachychoroid. We sutured vortex veins in eyes of wild type mice to imitate the vortex vein congestion in pachychoroid spectrum diseases. Fundus photography and ultra-widefield indocyanine green angiography showed dilated vortex veins from the posterior pole to the ampulla in eyes after induction of choroidal congestion. Optical coherence tomography and tissue sections presented choroidal thickening with dilatation of choroidal vessels. The RPE-choroid/retina thickness ratios on the tissue sections in the treated day 1 and day 7 groups were significantly greater than that in the control group (0.19±0.03 and 0.16±0.01 vs. 0.12±0.02, P<0.05 each). Moreover, immunohistochemistry using RPE flatmount revealed focal RPE degeneration in the treated eyes. Furthermore, inflammatory response-related genes were upregulated in eyes with choroidal congestion induction, and macrophages migrated into the thickened choroid. These results indicated that vortex vein congestion triggered some pachychoroid features. Thus, we have established a choroidal congestion mouse model by suturing vortex veins, which would potentially be useful for investigating the pathophysiology of pachychoroid spectrum diseases.
厚脉络膜谱系疾病已被描述为黄斑疾病谱系中的一种新的临床实体。“厚脉络膜”被定义为与扩张的脉络膜外层血管相关的脉络膜增厚，常伴有视网膜色素上皮（RPE）变性。尽管已经对厚脉络膜谱系疾病进行了各种临床研究，但其病理生理学尚未完全阐明。在本研究中，我们试图建立厚脉络膜小鼠模型。我们缝合野生型小鼠眼睛的涡静脉，以模拟厚脉络膜谱系疾病中的涡静脉充血。眼底照相和超广角吲哚菁绿血管造影显示，诱导脉络膜充血后，眼睛从后极到壶腹的涡静脉扩张。光学相干断层扫描和组织切片显示脉络膜增厚，脉络膜血管扩张。治疗第1天和第7天组组织切片上的RPE-脉络膜/视网膜厚度比显著高于对照组（分别为0.19±0.03和0.16±0.01对0.12±0.02，P<0.05）。此外，使用RPE平铺片的免疫组织化学显示治疗眼存在局灶性RPE变性。此外，诱导脉络膜充血后，眼睛中炎症反应相关基因上调，巨噬细胞迁移到增厚的脉络膜中。这些结果表明涡静脉充血引发了一些厚脉络膜特征。因此，我们通过缝合涡静脉建立了脉络膜充血小鼠模型，这可能有助于研究厚脉络膜谱系疾病的病理生理学。
