Yang Hyun Seung, Jo Yong-Ha, Kim Dongwoo, Choi Suho, Moon Byung Gil, Lee Youngseop, Kim Minji, Koo Donghoon, Kim Jeongmin
Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Department of Ophthalmology, Seoul Shinsegae Eye Center, Eui Jung Bu, Gyeonggi-do, Republic of Korea.
Invest Ophthalmol Vis Sci. 2025 Aug 1;66(11):39. doi: 10.1167/iovs.66.11.39.
To investigate whether Yes-associated protein (YAP), a key mechanotransduction effector, is associated with disease severity, surgical difficulty, and postoperative outcomes in epiretinal membrane (ERM) and to explore its prognostic relevance.
This prospective study enrolled patients undergoing vitrectomy for ERM. Pre- and postoperative best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including ERM stage, central subfield thickness (CST), inner retinal irregularity index (IRII), and ellipsoid zone disruption (EZD), were evaluated. Surgical grading of internal limiting membrane (ILM) adherence (SGIA) was applied to assess ILM adhesion and surgical difficulty. ERMs were analyzed by immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR), and vitreous cytokines were also analyzed.
Among 152 patients with ERM stages ≥ 2, 26.3% were classified as stage 2, 42.1% as stage 3, and 31.6% as stage 4. Advancing ERM stage was significantly associated with poorer BCVA, higher SGIA grade, and worsening OCT parameters. YAP expression (by qPCR and IHC) and vitreous TGF-β1 levels progressively increased with ERM stage. YAP on IHC showed stronger associations with postoperative CST, postoperative IRII, and both pre- and postoperative EZD, whereas TGF-β1 was more strongly linked to preoperative CST and IRII. YAP also correlated independently with SGIA grade. Multivariate analysis identified YAP expression and SGIA grade as independent predictors of postoperative BCVA and visual improvement.
ILM adhesion and surgical difficulty increase with ERM progression. YAP expression reflects ERM stage, ILM adhesion-related surgical complexity, postoperative retinal remodeling, and visual outcomes, independent of TGF-β pathways. These findings highlight YAP-mediated mechanotransduction as a key contributor to ERM pathophysiology and prognosis.
研究关键机械转导效应因子Yes相关蛋白（YAP）是否与视网膜前膜（ERM）的疾病严重程度、手术难度及术后预后相关，并探讨其预后相关性。
本前瞻性研究纳入了因ERM接受玻璃体切除术的患者。评估术前和术后的最佳矫正视力（BCVA）以及光学相干断层扫描（OCT）参数，包括ERM分期、中心子野厚度（CST）、视网膜内层不规则指数（IRII）和椭圆体带破坏（EZD）。应用内界膜（ILM）粘连手术分级（SGIA）来评估ILM粘连情况和手术难度。通过免疫组织化学（IHC）和定量聚合酶链反应（qPCR）分析ERM，并分析玻璃体细胞因子。
在152例ERM分期≥2期的患者中，26.3%为2期，42.1%为3期，31.6%为4期。ERM分期进展与较差的BCVA、较高的SGIA分级以及OCT参数恶化显著相关。YAP表达（通过qPCR和IHC）以及玻璃体TGF-β1水平随ERM分期逐渐升高。IHC检测的YAP与术后CST、术后IRII以及术前和术后EZD均显示出更强的相关性，而TGF-β1与术前CST和IRII的关联更强。YAP还与SGIA分级独立相关。多因素分析确定YAP表达和SGIA分级是术后BCVA和视力改善的独立预测因素。
ILM粘连和手术难度随ERM进展而增加。YAP表达反映了ERM分期、与ILM粘连相关的手术复杂性、术后视网膜重塑以及视力预后，独立于TGF-β途径。这些发现突出了YAP介导的机械转导是ERM病理生理学和预后的关键因素。
