Omi Masatoshi, Yamada Haruhiko, Takahashi Hajime, Mori Hidetsugu, Oba Shimpei, Hattori Yuki, Yokota Kaito, Toyama Keiko, Takahashi Kanji
Department of Ophthalmology, Kansai Medical University, Hirakata, Japan.
Heliyon. 2024 Mar 1;10(6):e27160. doi: 10.1016/j.heliyon.2024.e27160. eCollection 2024 Mar 30.
Retinal vein occlusion (RVO) can lead to visual impairment, but the development of collateral vessels can sometimes mitigate significant damage. This study aimed to investigate the relationship between collateral vessels and hypertension, the most common underlying condition associated with RVO, by comparing spontaneously hypertensive rats (SHRs) and wild-type Wister rats (WWRs). We also examined the differences between WWRs and SHRs in terms of sphingosine 1-phosphate receptor 1 (S1PR1) expression and its product nitric oxide synthase 3 (NOS3) expression, which are involved in the formation of collateral vessels after vascular occlusion.
Laser photocoagulation (PC) was used to occlude one randomly selected retinal vein in WWRs and SHRs, and the area surrounding the occluded vessel was examined using optical coherence tomography angiography. If reperfusion of the occluded vessel occurred within 2 weeks, the vessel was re-occluded repeatedly by PC. The number of eyes with successfully occluded vessels accompanied by collateral vessels was recorded. Then, WWRs and SHRs were divided into the following four groups: 1) control (no treatment), 2) vehicle (20% DMSO), 3) S1PR1 agonist (2 mg/mL SEW2871), and 4) S1PR1 antagonist (0.25 mg/mL VPC 23019) groups. The drugs were administered intravitreally in all groups except the control. The number of laser shots required for successful RVO was recorded. Histological evaluation and quantitative real-time PCR of S1PR1 and NOS3 were performed to elucidate the mechanisms underlying collateral vessel formation.
The proportion of eyes achieving successful vein occlusion was lower in SHRs (4/12 eyes, 33.3%) than in WWRs (8/10 eyes, 80%, p = 0.043). NOS3 expression at 6 h after PC was significantly higher in WWRs than in SHRs (p = 0.021). In WWRs treated with SEW2871, vein occlusion failed in 7 of 10 eyes (70%). The expression of NOS3 was significantly higher in the SEW2871 treatment group than in the untreated group (p < 0.001). Furthermore, NOS3 expression was significantly higher after SEW2871 treatment in WWRs than in SHRs (p = 0.011).
In hypertensive environments, collateral vessels are less likely to develop, and S1PR1 may be involved in this phenomenon.
视网膜静脉阻塞（RVO）可导致视力损害，但侧支血管的形成有时可减轻严重损害。本研究旨在通过比较自发性高血压大鼠（SHR）和野生型Wister大鼠（WWR），探讨侧支血管与高血压（RVO最常见的潜在相关疾病）之间的关系。我们还研究了WWR和SHR在鞘氨醇-1-磷酸受体1（S1PR1）表达及其产物一氧化氮合酶3（NOS3）表达方面的差异，这些与血管阻塞后侧支血管的形成有关。
采用激光光凝（PC）法阻塞WWR和SHR中随机选择的一条视网膜静脉，并用光学相干断层扫描血管造影术检查阻塞血管周围区域。如果阻塞血管在2周内发生再灌注，则通过PC反复重新阻塞该血管。记录成功阻塞血管并伴有侧支血管的眼数。然后，将WWR和SHR分为以下四组：1）对照组（未治疗）、2）溶剂组（20%二甲基亚砜）、3）S1PR1激动剂组（2 mg/mL SEW2871）和4）S1PR1拮抗剂组（0.25 mg/mL VPC 23019）。除对照组外，所有组均通过玻璃体腔内注射给药。记录成功实现RVO所需的激光照射次数。进行组织学评估以及S1PR1和NOS3的定量实时PCR，以阐明侧支血管形成的潜在机制。
SHR中成功实现静脉阻塞的眼比例（(4/12)眼，33.3%）低于WWR（(8/10)眼，80%，(p = 0.043)）。PC后6小时，WWR中NOS3的表达显著高于SHR（(p = 0.021)）。在接受SEW2871治疗的WWR中，(10)眼中有(7)眼（70%）静脉阻塞失败。SEW2871治疗组中NOS3的表达显著高于未治疗组（(p < 0.001)）。此外，SEW2871治疗后WWR中NOS3的表达显著高于SHR（(p = 0.011)）。
在高血压环境中，侧支血管形成的可能性较小，且S1PR1可能参与了这一现象。
