Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Front Immunol. 2023 Jan 25;13:1089286. doi: 10.3389/fimmu.2022.1089286. eCollection 2022.
HTLV-1 (human T-cell lymphotropic virus type 1) is a retrovirus that infects approximately 20 million people worldwide. Many diseases are caused by this virus, including HTLV-1-associated myelopathy, adult T-cell leukemia, and HTLV-1 uveitis. Intraocular anti-vascular endothelial growth factor (VEGF) antibody injection has been widely used in ophthalmology, and it is reportedly effective against age-related macular degeneration, complications of diabetic retinopathy, and retinal vein occlusions. HTLV-1 mimics VEGF, the predominant isoform of VEGF, to recruit neuropilin-1 and heparan sulfate proteoglycans. VEGF is also a selective competitor of HTLV-1 entry. Here, we investigated the effects of an anti-VEGF antibody on ocular status under conditions of HTLV-1 infection .
We used MT2 and TL-Om1 cells as HTLV-1-infected cells and Jurkat cells as controls. Primary human retinal pigment epithelial cells (HRPEpiCs) and ARPE19 HRPEpiCs were used as ocular cells; MT2/TL-Om1/Jurkat cells and HRPEpiCs/ARPE19 cells were co-cultured to simulate the intraocular environment of HTLV-1-infected patients. Aflibercept was administered as an anti-VEGF antibody. To avoid possible T-cell adhesion, we lethally irradiated MT2/TL-Om1/Jurkat cells prior to the experiments.
Anti-VEGF antibody treatment had no effect on activated NF-κB production, inflammatory cytokines, chemokines, HTLV-1 proviral load (PVL), or cell counts in the retinal pigment epithelium (RPE) under MT2 co-culture conditions. Under TL-Om1 co-culture conditions, anti-VEGF antibody treatment did not affect the production of activated NF-κB, chemokines, PVL, or cell counts, but production of the inflammatory cytokine IL-6 was increased. In addition, anti-VEGF treatment did not affect PVL in HTLV-1-infected T cells.
This preliminary assessment indicates that intraocular anti-VEGF antibody treatment for HTLV-1 infection does not exacerbate HTLV-1-related inflammation and thus may be safe for use.
HTLV-1（人类 T 细胞淋巴病毒 1 型）是一种逆转录病毒，全球约有 2000 万人感染。这种病毒会导致多种疾病，包括 HTLV-1 相关性脊髓病、成人 T 细胞白血病和 HTLV-1 葡萄膜炎。眼内抗血管内皮生长因子（VEGF）抗体注射已在眼科广泛应用，据报道对年龄相关性黄斑变性、糖尿病视网膜病变并发症和视网膜静脉阻塞有效。HTLV-1 模拟 VEGF，即 VEGF 的主要同工型，以招募神经纤毛蛋白 1 和肝素硫酸蛋白聚糖。VEGF 也是 HTLV-1 进入的选择性竞争物。在这里，我们研究了在 HTLV-1 感染情况下抗 VEGF 抗体对眼部状态的影响。
我们使用 MT2 和 TL-Om1 细胞作为 HTLV-1 感染细胞，Jurkat 细胞作为对照。原代人视网膜色素上皮细胞（HRPEpiCs）和 ARPE19 HRPEpiCs 用作眼部细胞；MT2/TL-Om1/Jurkat 细胞和 HRPEpiCs/ARPE19 细胞共培养模拟 HTLV-1 感染患者的眼内环境。给予 aflibercept 作为抗 VEGF 抗体。为避免可能的 T 细胞黏附，我们在实验前对 MT2/TL-Om1/Jurkat 细胞进行致死性照射。
在 MT2 共培养条件下，抗 VEGF 抗体治疗对激活的 NF-κB 产生、炎症细胞因子、趋化因子、HTLV-1 前病毒载量（PVL）或视网膜色素上皮细胞（RPE）中的细胞计数没有影响。在 TL-Om1 共培养条件下，抗 VEGF 抗体治疗不影响激活的 NF-κB、趋化因子、PVL 或细胞计数的产生，但炎症细胞因子 IL-6 的产生增加。此外，抗 VEGF 治疗对 HTLV-1 感染 T 细胞中的 PVL 没有影响。
本初步评估表明，眼内抗 VEGF 抗体治疗 HTLV-1 感染不会加重 HTLV-1 相关炎症，因此可能安全使用。
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