Article Text

PDF

FRI0027 5-aminolevulinic acid induced protoporphyrin ix formation in arthritic synovial tissues: an approach for synovial photodynamic therapy in arthritis
  1. G Kirdaite1,
  2. N Lange2,
  3. N Busso1,
  4. H Van den Bergh2,
  5. P Kucera3,
  6. A So1
  1. 1Laboratoire de Rhumatologie, Université de Lausanne
  2. 2DGR
  3. 3Institut de Physiologie, Université de Lausanne, Lausanne, Switzerland

Abstract

Objectives To determine the optimal conditions for synovial accumulation of protoporphyrin IX (PpIX) and light induced synovial cytotoxicity in arthritis in vitro and in vivo.

Methods In vitro studies: Synovial biopsies from patients with osteoarthritis (OA, n = 9), rheumatoid arthritis (RA, n = 3) and synovial tissues from mice with antigen-induced arthritis (AIA, n = 9) were incubated with different concentrations of 5-aminolevulinic acid hexyl-ester (h-ALA), a protoporphyrin IX (PpIX) precursor. Tissue PpIX content was determined by microspectrofluorometry. Following photoexcitation, the synovial tissues were evaluated by Sytox-Green fluorescence for cell death.

Animal studies: h-ALA was injected intra-articularly into knee joints of mice with AIA (n = 40). Following photodynamic therapy (PDT) in vivo, joint inflammation was assessed by technetium scintigraphy and histology.

Results In human biopsies, the highest fluorescence intensity was observed after incubation with 0.5–1 mM h-ALA. Kinetic studies showed that PpIX accumulation in human tissues reached a peak at 3 h in OA and increased linearly up to 6 h in RA. Murine tissues showed highest fluorescence intensity at a concentration of 4 mM in vitro and 8 mM in vivo. By fluorescence microscopy, PpIX was localised to the synovial lining layer, endothelial cells and macrophages. Irradiation of pre-incubated tissues in vitro led to significant cell death. PDT in vivo in AIA led to a statistically significant reduction of histological parameters of joint damage in irradiated joints.

Conclusion Our findings suggest that PDT based on PpIX accumulation in the synovial membrane may be a rational basis for photodynamic synovectomy in arthritic diseases.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.