State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.
Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou 515041, China.
Biomolecules. 2023 Oct 17;13(10):1532. doi: 10.3390/biom13101532.
Hypoxia-induced retinal neovascularization is a leading cause of blindness worldwide. Oxygen-induced retinopathy (OIR) mouse, a well-established angiogenesis model, has been extensively used to evaluate the effect of anti-angiogenic agents through intravitreal injection. Here, we serendipitously found that the needles used for intravitreal injection caused an unexpected "anti-angiogenic" effect in the OIR mice. To evaluate the effects of various intravitreal puncture sizes on retinal neovascularization and explore the potential underlying mechanism, intravitreal punctures using 0.5 mm (25 G), 0.3 mm (30 G), or 0.21 mm (33 G) needles were performed in OIR mice. Compared with 0.3 mm and 0.21 mm puncture, the 0.5 mm puncture remarkably suppressed the formation of pathological angiogenesis, inhibited vascular leakage, and remodeled the retinal vasculature. Mechanistically, the 0.5 mm puncture induced a substantial reduction in intraocular pressure (IOP), leading to an improvement in oxygen partial pressure (pO) and significant reduction in Hif1a expression, resulting in resolution of angiogenic and inflammatory responses. Furthermore, IOP-lowering drugs, Travatan or Azarga, also promoted the alleviation of hypoxia and exhibited a potent anti-angiogenesis efficacy. Our study revealed an acute and significant reduction in IOP caused by a large puncture, which could remarkably suppress HIF-1α-mediated retinal neovascularization, indicating that lowering IOP may be a promising therapeutic avenue for treating retinal neovascular diseases.
缺氧诱导的视网膜新生血管是全球范围内导致失明的主要原因。氧诱导视网膜病变（OIR）小鼠是一种成熟的血管生成模型，已被广泛用于通过玻璃体内注射评估抗血管生成药物的效果。在这里，我们偶然发现，用于玻璃体内注射的针头在 OIR 小鼠中引起了意想不到的“抗血管生成”作用。为了评估各种玻璃体内穿刺大小对视网膜新生血管的影响，并探讨潜在的机制，我们在 OIR 小鼠中进行了使用 0.5 毫米（25G）、0.3 毫米（30G）或 0.21 毫米（33G）针头的玻璃体内穿刺。与 0.3 毫米和 0.21 毫米穿刺相比，0.5 毫米穿刺显著抑制病理性血管生成的形成，抑制血管渗漏，并重塑视网膜血管。在机制上，0.5 毫米穿刺导致眼内压（IOP）显著降低，从而改善氧分压（pO），并显著降低 Hif1a 表达，从而解决血管生成和炎症反应。此外，降低 IOP 的药物 Travatan 或 Azarga 也促进了缺氧的缓解，并表现出强大的抗血管生成作用。我们的研究揭示了大穿刺引起的 IOP 急性和显著降低，可显著抑制 HIF-1α介导的视网膜新生血管形成，表明降低 IOP 可能是治疗视网膜新生血管疾病的有前途的治疗途径。
