Open AccessProtoporphyrin IX photodynamic therapy for synovitis
Author(s) -
Kirdaite Gailute,
Lange Norbert,
Busso Nathalie,
Van Den Bergh Hubert,
Kucera Pavel,
So Alexander
Publication year - 2002
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.10199
Subject(s) - photodynamic therapy , synovial membrane , synovitis , arthritis , pathology , rheumatoid arthritis , protoporphyrin ix , chemistry , synovial fluid , cytotoxicity , synovectomy , osteoarthritis , in vivo , medicine , in vitro , immunology , biology , biochemistry , organic chemistry , alternative medicine , microbiology and biotechnology
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.