Photodynamic therapy with ring-fused chlorins: a vision-preserving approach for retinoblastoma
Joana Margarido1, Catarina Mestre1,2, Tarcísio Guimarães1,2,3
1Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO) and Institute of Biophysics, Faculty of Medicine, 3000-548, Coimbra, Portugal.
Background:
This study aimed to use photodynamic therapy with ring-fused chlorins to treat Retinoblastoma, focusing on the therapeutic efficacy of photodynamic therapy and ensuring its safety.
Methods:
Three photosensitisers were evaluated in vitro using Y79-GFP-Luc cells to assess metabolic activity, viability, cell death mechanisms, and cell cycle modulation. In vivo efficacy was tested using an orthotopic xenograft model, assessed by optical coherence tomography, electroretinography, bioluminescence imaging, and immunohistochemistry.
Results:
The dihydroxymethyl derivative (Px1) emerged as the most potent (IC50 = 57.21 nM), inducing significant apoptosis and necrosis, confirmed by morphological analysis. In vivo studies suggested that photodynamic therapy preserves retinal architecture and neuronal responses in the early stages of disease, based on qualitative functional assessments. Bioluminescence imaging showed that photodynamic therapy reduced tumour size in animals with smaller lesions, although partial regrowth was noted after one week, highlighting the potential need for multiple treatment sessions. However, the treatment did not prevent disease progression in eyes with larger tumours. Immunohistochemistry further demonstrated that photodynamic therapy did not induce apoptosis in healthy retinal cells, significantly decreasing the proliferation marker Ki67 in tumour tissue. Microglial and astroglial reactivity remained minimal in healthy retinas upon photodynamic therapy, whereas tumour-bearing eyes exhibited glial activation.
Conclusion:
Overall, the research confirmed that Px1-based photodynamic therapy has cytotoxic potential against Retinoblastoma, highlighting its promise as a treatment option for Retinoblastoma lesions while maintaining retinal integrity and function. Future studies should explore repeated or combination treatments to enhance tumour control in advanced disease, thereby accelerating the potential clinical translation of this approach for childhood Retinoblastoma.
