Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Tomey Corporation, Nagoya, Japan.
Sci Rep. 2022 Jun 22;12(1):10535. doi: 10.1038/s41598-022-14637-5.
The intraocular pressure (IOP)-lowering mechanisms of micropulse laser trabeculoplasty (MLT) remain unclear. The present study was performed to investigate the mechanism of action of MLT, and to determine whether the pigmentation intensity of trabecular meshwork (TM) cells is associated with the treatment effects. Primary human TM cells were exposed to melanin granules to artificially introduce different levels of pigmentation. Micropulse (MP) laser irradiation was performed, and interleukin (IL)-1α/β, matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and extracellular matrix (ECM) protein expression were evaluated by RT-qPCR and immunocytochemistry. IL-1α/β and MMP-1, -3, and -9 mRNA expression were significantly upregulated at 4 and 24 h after MP laser irradiation, respectively, but there were no significant changes in TIMP expression. The extent of these upregulation was greater in cells with strong pigmentation intensity. Protein expressions of fibronectin and collagen I were significantly decreased in cells with strong staining intensity. These results suggested that MP laser irradiation alter the MMP/TIMP ratio and enhance ECM turnover, resulting in increased outflow of aqueous humor. The pigmentation intensity of the TM tissues may affect the treatment efficacy of MLT, because TM cells with strong staining intensity showed a significantly enhanced response to MP laser irradiation.
眼内压(IOP)降低机制的微脉冲激光小梁成形术(MLT)仍然不清楚。本研究旨在探讨 MLT 的作用机制,并确定小梁网(TM)细胞的色素沉着强度是否与治疗效果相关。将原代人 TM 细胞暴露于黑色素颗粒中,人为引入不同水平的色素沉着。进行微脉冲(MP)激光照射,并通过 RT-qPCR 和免疫细胞化学评估白细胞介素(IL)-1α/β、基质金属蛋白酶(MMPs)、金属蛋白酶组织抑制剂(TIMPs)和细胞外基质(ECM)蛋白的表达。MP 激光照射后 4 和 24 小时,IL-1α/β 和 MMP-1、-3 和 -9 mRNA 表达分别显著上调,但 TIMP 表达没有显著变化。色素沉着强度较强的细胞中,这些上调的程度更大。强染色强度的细胞中纤维连接蛋白和 I 型胶原的蛋白表达明显降低。这些结果表明,MP 激光照射改变了 MMP/TIMP 比值,增强了细胞外基质的周转,导致房水流出增加。TM 组织的色素沉着强度可能会影响 MLT 的治疗效果,因为染色强度较强的 TM 细胞对 MP 激光照射表现出明显增强的反应。