评估少年特发性关节炎相关性葡萄膜炎的血管生成相关参数。
Assessment of angiogenesis-related parameters in juvenile idiopathic arthritis-associated uveitis.
机构信息
Department of Ophthalmology and Ophtha-Lab, St. Franziskus-Hospital, Hohenzollernring 74, 48145, Münster, Germany.
University of Duisburg-Essen, Essen, Germany.
出版信息
Mol Biol Rep. 2022 Jul;49(7):6093-6102. doi: 10.1007/s11033-022-07398-x. Epub 2022 Apr 1.
PURPOSE
Juvenile idiopathic arthritis-associated uveitis (JIAU) may run a chronic and treatment-resistant course, and occasionally, alterations of the iris vasculature may be observed clinically.
METHODS
Iris tissue (IT), aqueous humor (AH) and serum samples from patients with clinically inactive JIAU (n = 30), acute anterior uveitis (AAU; n = 18), and primary open angle glaucoma (POAG; n = 20) were obtained during trabeculectomy or cataract surgery. Samples were analyzed by RNA-Seq, qRT-PCR, LC-IMS, Western-Blot, and LEGENDplex™ analysis. Pattern of iris vasculature in JIAU patients was assessed qualitatively via fluorescein and indocyanine green angiography (FLA/ICGA).
RESULTS
RNA-Seq of IT showed significantly differential expression (DE) of 136 genes between JIAU and POAG, of which 15 were associated with angiogenesis. qRT-PCR, performed to validate RNA-Seq results, showed upregulation of the angiogenesis-related genes Kdr, Angpt-1, Tie-1, Tie-2 and Mmrn2 in IT (JIAU vs POAG, p > 0.05). LC-IMS of IT revealed a total number of 56 DE proteins (JIAU vs POAG), of which Angiopoetin, Lumican and Decorin were associated with angiogenesis and showed increased (p > 0.05) expression on Western-Blot analysis. LEGENDplex™ analysis showed upregulation of ANGPT-2 in AH from JIAU compared to AAU and POAG, whereas VEGF was upregulated in AAU. Iris vascular leakage, hypoperfusion and neovascularization were observed by FLA/ICGA in JIA patients with treatment-refractory complicated course of uveitis.
CONCLUSION
Angiogenesis-related factors could play a role in long-standing complicated JIAU, leading to clinically visible alterations in selected cases.
目的
幼年特发性关节炎相关性葡萄膜炎（JIAU）可能呈慢性、治疗抵抗性病程，偶尔会观察到虹膜血管系统的改变。
方法
在小梁切除术或白内障手术期间，从患有临床静止性 JIAU（n=30）、急性前葡萄膜炎（AAU；n=18）和原发性开角型青光眼（POAG；n=20）的患者中获取虹膜组织（IT）、房水（AH）和血清样本。通过 RNA-Seq、qRT-PCR、LC-IMS、Western-Blot 和 LEGENDplexTM 分析对样本进行分析。通过荧光素和吲哚青绿血管造影（FLA/ICGA）对 JIAU 患者的虹膜血管模式进行定性评估。
结果
IT 的 RNA-Seq 显示 JIAU 和 POAG 之间有 136 个基因存在显著差异表达（DE），其中 15 个与血管生成有关。为验证 RNA-Seq 结果而进行的 qRT-PCR 显示，IT 中血管生成相关基因 Kdr、Angpt-1、Tie-1、Tie-2 和 Mmrn2 的表达上调（JIAU 与 POAG 相比，p>0.05）。IT 的 LC-IMS 显示 56 个 DE 蛋白（JIAU 与 POAG），其中 Angiopoetin、Lumican 和 Decorin 与血管生成有关，Western-Blot 分析显示表达增加（p>0.05）。LEGENDplexTM 分析显示 JIAU 患者 AH 中的 ANGPT-2 上调，与 AAU 和 POAG 相比，而 VEGF 在 AAU 中上调。在治疗抵抗性、复杂病程的葡萄膜炎 JIA 患者中，通过 FLA/ICGA 观察到虹膜血管渗漏、灌注不足和新生血管形成。
结论
血管生成相关因子可能在长期复杂的 JIAU 中发挥作用，导致在某些情况下出现临床可见的改变。
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