da Silva Costa Sueli Matilde, Ito Mirta Tomie, da Cruz Pedro Rodrigues Sousa, De Souza Bruno Batista, Rios Vinicius Mandolesi, Bertozzo Victor de Haidar E, Camargo Ana Carolina Lima, Viturino Marina Gonçalves Monteiro, Lanaro Carolina, de Albuquerque Dulcinéia Martins, do Canto Amanda Morato, Saad Sara Teresinha Olalla, Ospina-Prieto Stephanie, Ozelo Margareth Castro, Costa Fernando Ferreira, de Melo Mônica Barbosa
Center for Molecular Biology and Genetic Engineering, State University of Campinas-UNICAMP, Campinas, Brazil.
Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas-UNICAMP, Campinas, Brazil.
Exp Biol Med (Maywood). 2024 Jul 24;249:10070. doi: 10.3389/ebm.2024.10070. eCollection 2024.
HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes (log2FoldChange = 4.32, FDR = 1.35E-11) and (log2FoldChange = 3.36 FDR = 1.59E-07). , an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis.
HbSC病是镰状细胞病的一种较轻形式，更频繁地影响视网膜，患者发生增殖性视网膜病变的几率更高，这种病变可发展至视力丧失。本研究旨在确定与增殖性镰状细胞视网膜病变（PSCR）病理生理学相关的内皮细胞衍生分子表达的差异。采用RNA测序比较了患有SC血红蛋白病和增殖性视网膜病变的患者（n = 5）与无视网膜病变的SC患者（n = 3）循环内皮集落形成细胞的基因表达谱。使用实时聚合酶链反应（qRT-PCR）验证RNA测序结果。共发现134个差异表达基因（DEG）。DEG主要与血管舒张、I型干扰素信号传导、先天免疫和血管生成相关。在鉴定出的DEG中，我们突出显示上调程度最高的基因（log2倍变化= 4.32，FDR = 1.35E-11）和（log2倍变化= 3.36，FDR = 1.59E-07）。一种轴突导向受体，促进内皮细胞迁移，并有助于视网膜血管生成和病理性眼新生血管形成的发展。内皮细胞一种氨基酸（AA）转运蛋白，通过控制AA营养物质的摄取来调节发育性和病理性视网膜血管生成，AA营养物质可作为内皮细胞（EC）增殖的代谢燃料，从而促进血管生成。我们的数据为阐明PSCR的分子病理生理学迈出了重要一步，这可能解释了血红蛋白病患者眼部表现的差异，并为抑制病理性血管生成的新替代策略提供了见解。
