Pilotto Elisabetta, Midena Giulia, Torresin Tommaso, De Mojà Gilda, Bacelle Maria Laura, Ferrara Alfonso Massimiliano, Zovato Stefania, Midena Edoardo
Department of Ophthalmology, University of Padova, 35128 Padova, Italy.
ERN-EYE Center, University Hospital of Padova, 35128 Padova, Italy.
Cancers (Basel). 2021 Dec 30;14(1):170. doi: 10.3390/cancers14010170.
Von Hippel-Lindau (VHL) disease is a neoplastic syndrome caused by a mutation of the VHL tumor suppressor gene. Retinal hemangioblastoma (RH) is a vascularized tumor and represents the most common ocular manifestation of this disease. At the retinal level, VHL protein is able to regulate tumor growth, angiogenic factors, and neuroinflammation, probably stimulating retinal glial cells. The aim of the present study was to analyze in vivo the optical coherence tomography (OCT) biomarkers of retinal macroglia and microglia in a cohort of VHL patients.
The mean thicknesses of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and peripapillary retinal nerve fiber layer (pRNFL) were measured with OCT as biomarkers of retinal macroglia. OCT images were also analyzed to detect and quantify hyperreflective retinal foci (HRF), a biomarker of retinal activated microglia.
61 eyes of 61 VHL patients (22 eyes (36.07%) with peripheral RH and 39 eyes (63.93%) without RH) and 28 eyes of 28 controls were evaluated. pRNFL was thinner in VHL patients ( < 0.05) and in VHL without RH ( < 0.01) compared to controls, and thicker in VHL patients with RH than in those without RH ( < 0.05). The thickness of mRNFL ( < 0.0001) and GCL ( < 0.05) was reduced in VHL patients and in VHL without RH compared to controls, whereas mRNFL ( < 0.0001) and GCL ( < 0.05) were increased in VHL patients with RH compared to those without RH. HRF were significantly higher in number in VHL patients and in VHL without RH, than in controls, and significantly lower ( < 0.05) in the eyes of VHL patients with RH, than in those without RH.
The OCT analysis, which detects and allows to quantify the biomarkers of retinal microglia (HRF) and macroglia (pRNFL, mRNFL and GCL), showed a different behavior of these two retinal glial cells populations in VHL patients, related to the presence or absence of peripheral RH. These data allow to hypothesize a novel pathophysiologic pathway of retinal hemangioblastoma in VHL disease.
冯·希佩尔-林道（VHL）病是一种由VHL肿瘤抑制基因突变引起的肿瘤综合征。视网膜血管瘤（RH）是一种血管化肿瘤，是该疾病最常见的眼部表现。在视网膜层面，VHL蛋白能够调节肿瘤生长、血管生成因子和神经炎症，可能是通过刺激视网膜神经胶质细胞来实现的。本研究的目的是在一组VHL患者中对视网膜大胶质细胞和小胶质细胞的光学相干断层扫描（OCT）生物标志物进行体内分析。
使用OCT测量黄斑视网膜神经纤维层（mRNFL）、神经节细胞层（GCL）和视乳头周围视网膜神经纤维层（pRNFL）的平均厚度，作为视网膜大胶质细胞的生物标志物。还对OCT图像进行分析，以检测和量化高反射性视网膜病灶（HRF），这是视网膜活化小胶质细胞的生物标志物。
评估了61例VHL患者的61只眼（22只眼（36.07%）有周边RH，39只眼（63.93%）无RH）和28例对照的28只眼。与对照组相比，VHL患者以及无RH的VHL患者的pRNFL更薄（<0.05），有RH的VHL患者的pRNFL比无RH的更厚（<0.05）。与对照组相比，VHL患者以及无RH的VHL患者的mRNFL厚度（<0.0001）和GCL厚度（<0.05）降低，而有RH的VHL患者的mRNFL（<0.0001）和GCL（<0.05）比无RH的增加。VHL患者以及无RH的VHL患者眼中的HRF数量显著高于对照组，有RH的VHL患者眼中的HRF数量显著低于无RH的患者（<0.05）。
OCT分析能够检测并量化视网膜小胶质细胞（HRF）和大胶质细胞（pRNFL、mRNFL和GCL）的生物标志物，结果显示在VHL患者中，这两种视网膜神经胶质细胞群体的行为因周边RH的有无而有所不同。这些数据有助于推测VHL病中视网膜血管瘤的一种新的病理生理途径。
