Protoporphyrin IX photodynamic therapy for synovitis.
- Kirdaite G University Hospital, Lausanne, Switzerland.
- Lange N
- Busso N
- Van Den Bergh H
- Kucera P
- So A
- 2002-07-13
Published in:
- Arthritis and rheumatism. - 2002
Animals
Biopsy
Humans
Mice
Mice, Inbred C57BL
Photochemotherapy
Photosensitizing Agents
Protoporphyrins
Synovial Membrane
Synovitis
English
OBJECTIVE
To determine the conditions for synovial accumulation of protoporphyrin IX (PpIX) and photodynamic therapy (PDT)-induced synovial cytotoxicity in vitro and in vivo.
METHODS
Synovial tissues were obtained from mice with antigen-induced arthritis (AIA) and incubated with different concentrations of 5-aminolevulinic acid hexyl ester (h-ALA), a PpIX precursor. Following photoexcitation, cell death in synovial tissues was evaluated by Sytox green fluorescence. PDT was performed after intraarticular injection of h-ALA into the knee joints of mice with AIA, and its effect on joint inflammation was assessed by technetium scintigraphy and histology. Synovial biopsy samples were obtained from patients with osteoarthritis (OA; n = 9) and rheumatoid arthritis (RA; n = 7) and studied for PDT-induced cytotoxicity in vitro.
RESULTS
Conversion of h-ALA to PpIX was observed in inflamed synovium in mice and humans. Cytotoxicity was confirmed by Sytox green staining in samples subjected to PDT. In the AIA model, injection of affected knees with h-ALA prior to PDT led to a statistically significant reduction of joint damage in the irradiated joints. The preferential transformation of h-ALA to PpIX in inflammatory tissues was confirmed in human synovial biopsy tissues, where RA samples showed higher tissue concentrations of PpIX following incubation with h-ALA than did OA samples. Fluorescence microscopy showed that PpIX was localized to the synovial lining layer, endothelial cells, and macrophages and induced cell death after PDT.
CONCLUSION
Our findings suggest that PDT based on the accumulation of PpIX in the synovial membrane may be a rational basis for photodynamic synovectomy in arthritic diseases.
To determine the conditions for synovial accumulation of protoporphyrin IX (PpIX) and photodynamic therapy (PDT)-induced synovial cytotoxicity in vitro and in vivo.
METHODS
Synovial tissues were obtained from mice with antigen-induced arthritis (AIA) and incubated with different concentrations of 5-aminolevulinic acid hexyl ester (h-ALA), a PpIX precursor. Following photoexcitation, cell death in synovial tissues was evaluated by Sytox green fluorescence. PDT was performed after intraarticular injection of h-ALA into the knee joints of mice with AIA, and its effect on joint inflammation was assessed by technetium scintigraphy and histology. Synovial biopsy samples were obtained from patients with osteoarthritis (OA; n = 9) and rheumatoid arthritis (RA; n = 7) and studied for PDT-induced cytotoxicity in vitro.
RESULTS
Conversion of h-ALA to PpIX was observed in inflamed synovium in mice and humans. Cytotoxicity was confirmed by Sytox green staining in samples subjected to PDT. In the AIA model, injection of affected knees with h-ALA prior to PDT led to a statistically significant reduction of joint damage in the irradiated joints. The preferential transformation of h-ALA to PpIX in inflammatory tissues was confirmed in human synovial biopsy tissues, where RA samples showed higher tissue concentrations of PpIX following incubation with h-ALA than did OA samples. Fluorescence microscopy showed that PpIX was localized to the synovial lining layer, endothelial cells, and macrophages and induced cell death after PDT.
CONCLUSION
Our findings suggest that PDT based on the accumulation of PpIX in the synovial membrane may be a rational basis for photodynamic synovectomy in arthritic diseases.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1002/art.10199
- PMID 12115245
- Persistent URL
- https://sonar.ch/global/documents/93595
Statistics
Document views: 30
File downloads:
- Full-text: 0