Eye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J Neuroinflammation. 2024 Nov 14;21(1):297. doi: 10.1186/s12974-024-03291-5.
Despite great advances in proliferative diabetic retinopathy (PDR) therapy over the last decades, one third of treated patients continue to lose vision. While resident vitreous macrophages called hyalocytes have been implicated in the pathophysiology of vitreoretinal proliferative disease previously, little is known about their exact role in PDR. In this study, we address molecular and cellular alterations in the vitreous of PDR patients as a means towards assessing the potential contribution of hyalocytes to disease pathogenesis.
A total of 55 patients were included in this study encompassing RNA-Sequencing analysis of hyalocytes isolated from the vitreous of PDR and control patients, multiplex immunoassay and ELISA analyses of vitreous samples from PDR and control patients, as well as isolation and immunohistochemical staining of cultured porcine hyalocytes. Transcriptional analysis revealed an enhanced inflammatory response of hyalocytes contributing to the cytokine pool within the vitreous of PDR patients by expressing interleukin-6, among others. Further, increased angiopoietin-2 expression indicated that hyalocytes from PDR patients undergo a proangiogenic shift and may thus mediate the formation of retinal neovascularizations, the hallmark of PDR. Finally, RNA-Sequencing revealed an upregulation of factors known from hemoglobin catabolism in hyalocytes from PDR patients. By immunohistochemistry, cultured porcine hyalocytes exposed to red blood cells were shown to engulf and phagocytose these, which reveals hyalocytes' potential to dispose of erythrocytes. Thus, our data suggest a potential role for vitreous macrophages in erythrophagocytosis and, thereby, clearance of vitreous hemorrhage, a severe complication of PDR.
Our results strongly indicate a critical role for vitreous hyalocytes in key pathophysiological processes of proliferative diabetic retinopathy: inflammation, angiomodulation and erythrophagocytosis. Immunomodulation of hyalocytes may thus prove an essential novel therapeutic approach in diabetic vitreoretinal disease.
尽管过去几十年在增殖性糖尿病视网膜病变 (PDR) 治疗方面取得了巨大进展，但仍有三分之一接受治疗的患者视力继续下降。虽然先前已经有研究表明，居住在玻璃体中的巨噬细胞（称为玻璃体细胞）与玻璃体视网膜增殖性疾病的病理生理学有关，但对于它们在 PDR 中的确切作用知之甚少。在这项研究中，我们研究了 PDR 患者玻璃体中的分子和细胞变化，以期评估玻璃体细胞对疾病发病机制的潜在贡献。
本研究共纳入 55 名患者，包括从 PDR 和对照组患者的玻璃体中分离的玻璃体细胞的 RNA 测序分析、PDR 和对照组患者玻璃体样本的多重免疫测定和 ELISA 分析，以及培养的猪玻璃体细胞的分离和免疫组织化学染色。转录分析显示，玻璃体细胞的炎症反应增强，通过表达白细胞介素 6 等细胞因子，有助于 PDR 患者玻璃体中的细胞因子库。此外，血管生成素-2 表达增加表明，PDR 患者的玻璃体细胞发生促血管生成转变，因此可能介导视网膜新生血管的形成，这是 PDR 的标志。最后，RNA 测序显示，PDR 患者的玻璃体细胞中上调了已知参与血红蛋白分解代谢的因子。通过免疫组织化学染色，暴露于红细胞的培养猪玻璃体细胞被证明可以吞噬和吞噬这些细胞，这揭示了玻璃体细胞处理红细胞的潜力。因此，我们的数据表明，玻璃体巨噬细胞在红细胞吞噬作用和清除玻璃体出血（PDR 的严重并发症）方面可能发挥重要作用。
我们的研究结果强烈表明，玻璃体玻璃体细胞在增殖性糖尿病视网膜病变的关键病理生理过程中发挥着关键作用：炎症、血管调节和红细胞吞噬作用。因此，玻璃体细胞的免疫调节可能成为糖尿病性玻璃体视网膜疾病的一种重要新的治疗方法。
