Hematoporphyrin derivative photoradiation induced damage to normal and tumor tissue of the pigmented rabbit eye

Abstract

Cytotoxicity induced by hematoporphyrin derivative (HpD) photoradiation in both normal and experimental tumor tissue of pigmented rabbit eyes has been examined. In addition, documentation of HpD induced fluorescence in ocular structures has also been obtained. Acute normal ocular tissue toxicity studies demonstrated that HpD (1-10 mg HpD/kg) followed 48 hours later by a transpupil irradiation of red light (635 nm, 36-90 J/cm2) resulted in demarcated areas of retinal damage. Long term (chronic) toxicity studies have shown that the initial damage to the retina was permanent but that no damage to the cornea, lens or vitreous could be observed during a 16 month follow-up. Visual and histological documentation have been obtained, following HpD photoradiation therapy (PRT), in rabbit eyes having heterotransplanted single nodule amelanotic melanomas. A toxic effect characterized by tumor blanching, edema and hemorrhage was observed within 24 hours of treatment. Histological examination obtained 24 hours following HpD PRT illustrated massive tumor tissue necrosis and vascular disruption. HpD PRT at clinically relevant doses was also shown to be effective in selectively curing the highly malignant amelanotic iris melanoma. It is concluded that HpD PRT may prove to be an effective modality for treating certain ocular tumors.

Induction of Prosurvival Molecules During Treatment: Rethinking Therapy Options for Photodynamic Therapy

“…Preclinical studies examined the cytotoxicity induced by hematoporphyrin derivative photoradiation in both normal and experimental tumor tissue in the eye. 1,2 "We looked at distribution and long-term effects of PDT in the eye and thought we were ready to do clinical work using PDT for retinoblastoma and a variety of adult ocular melanomas," revealed Dr. Gomer. The initial clinical results with ocular PDT were disappointing, he admitted.…”

Porphyrin Photosensitization and Phototherapy

“…Gomer et al (1984bGomer et al ( , 1985a have studied the effect of PDT on different normal tissues of rabbit's eyes as well as on tumors and concluded that the modality may be safe and effective for the treatment of ocular tumors.…”

Ineffective photodynamic therapy (PDT) in a poorly vascularized xenograft model

“…Although RB is highly curable by enucleation and/or radiotherapy, the morbidity of current treatment has made HPD-PDT an appealing prospect in the management of early, and particularly bilateral RB. The relatively easy access of light to the intraocular lesion (Gomer et al, 1984) and documented in-vitro responsiveness of RB to HPD-PDT (Sery, 1979) have encouraged further research.A xenograft model has been developed whereby human RB can be studied heterotransplanted into the anterior chamber of the nude (athymic) mouse eye (Gallie et al, 1977). Necrosis was documented histologically in very advanced tumours after HPD injection followed by PDT in the mouse (Benedict et al, 1980b).…”

“…Although RB is highly curable by enucleation and/or radiotherapy, the morbidity of current treatment has made HPD-PDT an appealing prospect in the management of early, and particularly bilateral RB. The relatively easy access of light to the intraocular lesion (Gomer et al, 1984) and documented in-vitro responsiveness of RB to HPD-PDT (Sery, 1979) have encouraged further research.…”