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玻璃体视网膜疾病患者眼内液中铜蓝蛋白和铁蛋白的变化:与神经炎症和玻璃膜疣形成的关系。

Ceruloplasmin and Ferritin Changes in Ocular Fluids from Patients with Vitreoretinal Diseases: Relation with Neuroinflammation and Drusen Formation.

作者信息

Esposito Graziana, Cosimi Pamela, Balzamino Bijorn Omar, Bruno Marisa, Squitti Rosanna, Dinice Lucia, Scarinci Fabio, Rongioletti Mauro Ciro Antonio, Cacciamani Andrea, Micera Alessandra

机构信息

Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS-Fondazione Bietti, 00184 Rome, Italy.

Surgical Retina Research Unit, IRCCS-Fondazione Bietti, 00184 Rome, Italy.

出版信息

Int J Mol Sci. 2025 Jun 30;26(13):6307. doi: 10.3390/ijms26136307.

Abstract

This pilot study explored whether the ceruloplasmin (CP) and ferritin (FT) levels in ocular fluids could serve as biomarkers for early neurodegenerative diseases (Alzheimer's, Parkinson's, and other dementias). CP and FT are known to modulate neurodegenerative tissue responses. We analysed aqueous and vitreous samples from 26 patients (8M/18F, aged 60-85) who were undergoing elective vitreoretinal (VR) surgery. Of these, 14 had idiopathic epiretinal membranes (ERMs), 6 had idiopathic macular holes (MH), and 6 were patients with Alzheimer's disease (AD) who presented with VR disorders (VRDs). CP, FT, and selected neuroinflammatory mediators such as interferon γ (IFN-γ), interleukin (IL-6), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were quantified. Odds ratio analysis was applied to assess the CP/FT ratio's association with subretinal drusen. We found distinct CP and FT profiles in VRD samples. In aqueous fluid, the CP increased and the FT decreased in early-stage ERM, which reduced the CP/FT ratio. Similar patterns were observed in vitreous fluid. The CP levels correlated with the VEGF (aqueous), IL-4 (vitreous), NGF, and BDNF levels; FT correlated with IL-6 and NGF. A higher CP/FT ratio was associated with increased risk for neurodegenerative conditions. Our findings support the quantification of CP and FT in ocular fluids as a promising approach for identifying early neurodegenerative changes and suggest that the CP/FT ratio may be linked to drusen imaging and clinical neurodegenerative history.

摘要

这项初步研究探讨了眼内液中的铜蓝蛋白(CP)和铁蛋白(FT)水平是否可作为早期神经退行性疾病(阿尔茨海默病、帕金森病和其他痴呆症)的生物标志物。已知CP和FT可调节神经退行性组织反应。我们分析了26例接受选择性玻璃体视网膜(VR)手术患者(8名男性/18名女性,年龄60 - 85岁)的房水和玻璃体样本。其中,14例患有特发性视网膜前膜(ERM),6例患有特发性黄斑裂孔(MH),6例为患有VR疾病(VRD)的阿尔茨海默病(AD)患者。对CP、FT以及选定的神经炎症介质,如干扰素γ(IFN - γ)、白细胞介素(IL - 6)、血管内皮生长因子(VEGF)、神经生长因子(NGF)和脑源性神经营养因子(BDNF)进行了定量分析。应用比值比分析来评估CP/FT比值与视网膜下玻璃膜疣的关联。我们在VRD样本中发现了不同的CP和FT特征。在房水中,早期ERM患者的CP升高而FT降低,这降低了CP/FT比值。在玻璃体液中观察到类似模式。CP水平与VEGF(房水)、IL - 4(玻璃体)、NGF和BDNF水平相关;FT与IL - 6和NGF相关。较高的CP/FT比值与神经退行性疾病风险增加相关。我们的研究结果支持对眼内液中的CP和FT进行定量分析,作为识别早期神经退行性变化的一种有前景的方法,并表明CP/FT比值可能与玻璃膜疣成像和临床神经退行性病史有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98b5/12250406/aeb4c28856cb/ijms-26-06307-g001.jpg

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