Biomaterial Database

Rabbit model of ocular indirect photodynamic therapy using a retinoblastoma xenograft. 2017

Jonathan W Kim, and Bradley Jacobsen, and Emily Zolfaghari, and Angela Ferrario, and Patricia Chevez-Barrios, and Jesse L Berry, and Diana K Lee, and Grecia Rico, and Ingy Madi, and Narsing Rao, and Kevin Stachelek, and Lei-Chi Wang, and Charles Gomer

Vision Center, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, 90027, USA. jwkim333@gmail.com.

OBJECTIVE The goal of this project was to demonstrate the feasibility of coupling the indirect ophthalmoscope laser delivery system with the 690 nm wavelength diode laser used to perform photodynamic therapy (PDT) in the treatment of retinoblastoma. METHODS For phase 1, a total of six pigmented rabbits were treated with the indirect laser delivery system. The laser source was provided by the Lumenis Opal 690 nm laser unit, delivered through a 810 nm Indirect ophthalmoscope headpiece and a hand-held 28-diopter indirect lens (1.0 mm spot size). Four rabbits received intravenous verteporfin at doses of 0.43 or 0.86 mg/kg, and two rabbits did not receive verteporfin (controls). A second phase of the study involved eight rabbits using a retinoblastoma xenograft to determine the effect of indirect PDT on subretinal tumors. RESULTS For phase 1, a total of 20 laser treatments were performed in the right eyes of six rabbits. Laser power levels ranged between 40 and 150 mW/cm2 and treatment duration ranged between 1 and 3 min. In the four rabbits that received verteporfin, focal retinal scars were noted at 40 mW/cm2 and higher power levels. In the two control rabbits that did not receive verteporfin, thermal burns were confirmed at 75 mW/cm2 and higher power levels. Histopathology showed focal retino-choroidal scars at the site of PDT treatment, without evidence of generalized ocular damage. Using the retinoblastoma xenograft, the indirect PDT system was shown to cause areas of tumor necrosis on histopathology. CONCLUSIONS The results of this pre-clinical study suggest verteporfin may be activated in the rabbit retina with the indirect delivery system and the 690 nm laser unit (i.e., Indirect PDT). Using verteporfin, treatment effects were observed at 40-50 mW/cm2 in the rabbit retina, while photocoagulation was achieved at 75 mW/cm2 and higher power levels. Fundoscopic and histopathologic examination of treated areas showed circumscribed areas of retinal damage and a lack of generalized ocular toxicity, suggesting that this modality may represent a safe and localized method for treating intraocular retinoblastoma.

UI	MeSH Term	Description	Entries
D007275	Injections, Intravenous	Injections made into a vein for therapeutic or experimental purposes.	Intravenous Injections,Injection, Intravenous,Intravenous Injection
D009374	Neoplasms, Experimental	Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.	Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D009887	Ophthalmoscopy	Examination of the interior of the eye with an ophthalmoscope.	Ophthalmoscopies
D010778	Photochemotherapy	Therapy using oral or topical photosensitizing agents with subsequent exposure to light.	Blue Light Photodynamic Therapy,Photodynamic Therapy,Red Light PDT,Red Light Photodynamic Therapy,Therapy, Photodynamic,Light PDT, Red,PDT, Red Light,Photochemotherapies,Photodynamic Therapies,Therapies, Photodynamic
D011166	Porphyrins	A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin.	Porphyrin
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D005240	Feasibility Studies	Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project.	Feasibility Study,Studies, Feasibility,Study, Feasibility
D000077362	Verteporfin	A benzoporphyrin derivative that is used in PHOTOCHEMOTHERAPY to treat wet type MACULAR DEGENERATION.	18-Ethenyl-4,4a-dihydro-3,4-bis(methoxycarbonyl)-4a,8,14,19-tetramethyl-23H,25H-benzo(b)porphine-9,13-dipropanoic acid monomethyl ester,BPD Verteporfin,BPD-MA,Benzoporphyrin Derivative Monoacid Ring A,Verteporphin,Visudyne
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012175	Retinoblastoma	A malignant tumor arising from the nuclear layer of the retina that is the most common primary tumor of the eye in children. The tumor tends to occur in early childhood or infancy and may be present at birth. The majority are sporadic, but the condition may be transmitted as an autosomal dominant trait. Histologic features include dense cellularity, small round polygonal cells, and areas of calcification and necrosis. An abnormal pupil reflex (leukokoria); NYSTAGMUS, PATHOLOGIC; STRABISMUS; and visual loss represent common clinical characteristics of this condition. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2104)	Glioblastoma, Retinal,Glioma, Retinal,Neuroblastoma, Retinal,Eye Cancer, Retinoblastoma,Familial Retinoblastoma,Hereditary Retinoblastoma,Sporadic Retinoblastoma,Cancer, Retinoblastoma Eye,Cancers, Retinoblastoma Eye,Eye Cancers, Retinoblastoma,Familial Retinoblastomas,Glioblastomas, Retinal,Gliomas, Retinal,Hereditary Retinoblastomas,Neuroblastomas, Retinal,Retinal Glioblastoma,Retinal Glioblastomas,Retinal Glioma,Retinal Gliomas,Retinal Neuroblastoma,Retinal Neuroblastomas,Retinoblastoma Eye Cancer,Retinoblastoma Eye Cancers,Retinoblastoma, Familial,Retinoblastoma, Hereditary,Retinoblastoma, Sporadic,Retinoblastomas,Retinoblastomas, Familial,Retinoblastomas, Hereditary,Retinoblastomas, Sporadic,Sporadic Retinoblastomas