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

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.

Keywords: Angiogenesis; Fluorescein angiography; ICG angiography; Juvenile idiopathic arthritis; Uveitis.

MeSH terms

  • Arthritis, Juvenile* / complications
  • Arthritis, Juvenile* / genetics
  • Glaucoma, Open-Angle*
  • Humans
  • Neovascularization, Pathologic / genetics
  • Trabeculectomy* / adverse effects
  • Uveitis* / complications
  • Uveitis, Anterior* / complications