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Assessment of angiogenesis-related parameters in juvenile idiopathic arthritis-associated uveitis

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Abstract

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.

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Data availability

The datasets presented in this study can be found in online repositories (NCBI GEO; GSE171745).

Code availability

Not applicable.

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Acknowledgements

The authors thank Doreen Ackermann for assistance with proteome analyses, Andrei Barysenka, Shirin Glander, Gerrit Randau and Anika Witten for support during RNASeq, Harutyun Melkonyan for assistance with qPCR, and Carsten Heinz, Jörg Koch, Björn Laffer and Christoph Tappeiner for help with patient sample and data collection.

Funding

Funded in part by German Ophthalmological Society (DOG), uveitis section.

Author information

Author notes

  1. Karoline Baquet-Walscheid and Lena Wildschütz have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Ophthalmology and Ophtha-Lab, St. Franziskus-Hospital, Hohenzollernring 74, 48145, Münster, Germany

    Karoline Baquet-Walscheid, Lena Wildschütz, Maren Kasper, Martin Busch, Dirk Bauer & Arnd Heiligenhaus

  2. University of Duisburg-Essen, Essen, Germany

    Karoline Baquet-Walscheid & Arnd Heiligenhaus

  3. Institute of Experimental Ophthalmology, University of Muenster, Münster, Germany

    Solon Thanos

  4. Core Facility Genomics, University of Muenster, Münster, Germany

    Monika Stoll

  5. Department “Genetic Epidemiology”, Institute of Human Genetics, University of Münster, Münster, Germany

    Monika Stoll

  6. Core Unit Proteomics, Interdisciplinary Center for Clinical Research, University of Muenster, Münster, Germany

    Simone König

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  1. Karoline Baquet-Walscheid
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by all authors. The first draft of the manuscript was written by KBW and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Karoline Baquet-Walscheid.

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Baquet-Walscheid, K., Wildschütz, L., Kasper, M. et al. Assessment of angiogenesis-related parameters in juvenile idiopathic arthritis-associated uveitis. Mol Biol Rep 49, 6093–6102 (2022). https://doi.org/10.1007/s11033-022-07398-x

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