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Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 12/2017

02.10.2017 | Basic Science

Rabbit model of ocular indirect photodynamic therapy using a retinoblastoma xenograft

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

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 12/2017

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Abstract

Purpose

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.
Literatur
1.
Zurück zum Zitat Fisher AM, Murphree AL, Gomer CJ (1995) Clinical and preclinical photodynamic therapy. Lasers Surg Med 17:2–31CrossRefPubMed Fisher AM, Murphree AL, Gomer CJ (1995) Clinical and preclinical photodynamic therapy. Lasers Surg Med 17:2–31CrossRefPubMed
2.
Zurück zum Zitat Gomer CJ, Ferrario A, Hayashi N, Rucker N, Szirth BC, Murphree AL (1988) Molecular, cellular, and tissue responses following photodynamic therapy. Lasers Surg Med 8:450–463CrossRefPubMed Gomer CJ, Ferrario A, Hayashi N, Rucker N, Szirth BC, Murphree AL (1988) Molecular, cellular, and tissue responses following photodynamic therapy. Lasers Surg Med 8:450–463CrossRefPubMed
3.
Zurück zum Zitat Gomer CJ, Ferrario A, Murphree AL (1987) The effect of localized porphyrin photodynamic therapy on the induction of tumour metastasis. Br J Cancer 56:27–32CrossRefPubMedPubMedCentral Gomer CJ, Ferrario A, Murphree AL (1987) The effect of localized porphyrin photodynamic therapy on the induction of tumour metastasis. Br J Cancer 56:27–32CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Gomer CJ, Hayashi N, Murphree AL (1987) The influence of sodium pentobarbital anesthesia on in vivo photodynamic therapy. Photochem Photobiol 46:843–846CrossRefPubMed Gomer CJ, Hayashi N, Murphree AL (1987) The influence of sodium pentobarbital anesthesia on in vivo photodynamic therapy. Photochem Photobiol 46:843–846CrossRefPubMed
5.
Zurück zum Zitat Gomer CJ, Rucker N, Razum NJ, Murphree AL (1985) In vitro and in vivo light dose rate effects related to hematoporphyrin derivative photodynamic therapy. Cancer Res 45:1973–1977PubMed Gomer CJ, Rucker N, Razum NJ, Murphree AL (1985) In vitro and in vivo light dose rate effects related to hematoporphyrin derivative photodynamic therapy. Cancer Res 45:1973–1977PubMed
6.
Zurück zum Zitat Gomer CJ, Rucker N, Ferrario A, Murphree AL (1986) Expression of potentially lethal damage in Chinese hamster cells exposed to hematoporphyrin derivative photodynamic therapy. Cancer Res 46:3348–3352PubMed Gomer CJ, Rucker N, Ferrario A, Murphree AL (1986) Expression of potentially lethal damage in Chinese hamster cells exposed to hematoporphyrin derivative photodynamic therapy. Cancer Res 46:3348–3352PubMed
7.
Zurück zum Zitat Gomer CJ, Rucker N, Murphree AL (1988) Transformation and mutagenic potential of porphyrin photodynamic therapy in mammalian cells. Int J Radiat Biol Relat Stud Phys Chem Med 53:651–659CrossRefPubMed Gomer CJ, Rucker N, Murphree AL (1988) Transformation and mutagenic potential of porphyrin photodynamic therapy in mammalian cells. Int J Radiat Biol Relat Stud Phys Chem Med 53:651–659CrossRefPubMed
8.
Zurück zum Zitat Murphree AL, Cote M, Gomer CJ (1987) The evolution of photodynamic therapy techniques in the treatment of intraocular tumors. Photochem Photobiol 46:919–923CrossRefPubMed Murphree AL, Cote M, Gomer CJ (1987) The evolution of photodynamic therapy techniques in the treatment of intraocular tumors. Photochem Photobiol 46:919–923CrossRefPubMed
9.
Zurück zum Zitat Liu LH, Ni C (1983) Hematoporphyrin phototherapy for experimental intraocular malignant melanoma. Arch Ophthalmol 101:901–903CrossRefPubMed Liu LH, Ni C (1983) Hematoporphyrin phototherapy for experimental intraocular malignant melanoma. Arch Ophthalmol 101:901–903CrossRefPubMed
10.
Zurück zum Zitat Sery TW, Dougherty TJ (1984) Photoradiation of rabbit ocular malignant melanoma sensitized with hematoporphyrin derivative. Curr Eye Res 3:519–528CrossRefPubMed Sery TW, Dougherty TJ (1984) Photoradiation of rabbit ocular malignant melanoma sensitized with hematoporphyrin derivative. Curr Eye Res 3:519–528CrossRefPubMed
11.
Zurück zum Zitat Ohnishi Y, Yamana Y, Minei M (1986) Photoradiation therapy using argon laser and a hematoporphyrin derivative for retinoblastoma--a preliminary report. Jpn J Ophthalmol 30:409–419PubMed Ohnishi Y, Yamana Y, Minei M (1986) Photoradiation therapy using argon laser and a hematoporphyrin derivative for retinoblastoma--a preliminary report. Jpn J Ophthalmol 30:409–419PubMed
13.
Zurück zum Zitat Gomer CJ, Jester JV, Razum NJ, Szirth BC, Murphree AL (1985) Photodynamic therapy of intraocular tumors: examination of hematoporphyrin derivative distribution and long-term damage in rabbit ocular tissue. Cancer Res 45:3718–3725PubMed Gomer CJ, Jester JV, Razum NJ, Szirth BC, Murphree AL (1985) Photodynamic therapy of intraocular tumors: examination of hematoporphyrin derivative distribution and long-term damage in rabbit ocular tissue. Cancer Res 45:3718–3725PubMed
14.
Zurück zum Zitat Schefler AC, Cicciarelli N, Feuer W, Toledano S, Murray TG (2007) Macular retinoblastoma: evaluation of tumor control, local complications, and visual outcomes for eyes treated with chemotherapy and repetitive foveal laser ablation. Ophthalmology 114:162–169CrossRefPubMed Schefler AC, Cicciarelli N, Feuer W, Toledano S, Murray TG (2007) Macular retinoblastoma: evaluation of tumor control, local complications, and visual outcomes for eyes treated with chemotherapy and repetitive foveal laser ablation. Ophthalmology 114:162–169CrossRefPubMed
15.
Zurück zum Zitat Shields CL, Shields JA, Kiratli H, De Potter PV (1995) Treatment of retinoblastoma with indirect ophthalmoscope laser photocoagulation. J Pediatr Ophthalmol Strabismus 32:317–322PubMed Shields CL, Shields JA, Kiratli H, De Potter PV (1995) Treatment of retinoblastoma with indirect ophthalmoscope laser photocoagulation. J Pediatr Ophthalmol Strabismus 32:317–322PubMed
16.
Zurück zum Zitat Masuyama Y, Fukuzaki M, Kodama Y, Baba Y, Sawada A (1984) Treatment of retinoblastoma with argon laser photocoagulation. J Pediatr Ophthalmol Strabismus 21:169–171PubMed Masuyama Y, Fukuzaki M, Kodama Y, Baba Y, Sawada A (1984) Treatment of retinoblastoma with argon laser photocoagulation. J Pediatr Ophthalmol Strabismus 21:169–171PubMed
17.
Zurück zum Zitat Augsburger JJ, Faulkner CB (1992) Indirect ophthalmoscope argon laser treatment of retinoblastoma. Ophthalmic Surg 23:591–593PubMed Augsburger JJ, Faulkner CB (1992) Indirect ophthalmoscope argon laser treatment of retinoblastoma. Ophthalmic Surg 23:591–593PubMed
18.
Zurück zum Zitat Abramson DH, Schefler AC (2004) Transpupillary thermotherapy as initial treatment for small intraocular retinoblastoma: technique and predictors of success. Ophthalmology 111:984–991CrossRefPubMed Abramson DH, Schefler AC (2004) Transpupillary thermotherapy as initial treatment for small intraocular retinoblastoma: technique and predictors of success. Ophthalmology 111:984–991CrossRefPubMed
19.
Zurück zum Zitat Zhu D, Berry JL, Ediriwickrema L, Wong K, Lee TC, Murphree AL, Kim JW, Jubran R (2015) Long-term outcomes of group B eyes in patients with retinoblastoma treated with short-course chemoreduction: experience from Children’s hospital Los Angeles/University of Southern California. Ocul Oncol Pathol 2(2):105–111CrossRefPubMedPubMedCentral Zhu D, Berry JL, Ediriwickrema L, Wong K, Lee TC, Murphree AL, Kim JW, Jubran R (2015) Long-term outcomes of group B eyes in patients with retinoblastoma treated with short-course chemoreduction: experience from Children’s hospital Los Angeles/University of Southern California. Ocul Oncol Pathol 2(2):105–111CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Seshadri M, Belinier DA, Vaughan LA, Spernyak JA, Mazurchuk R, Foster TH, Henderson BW (2008) Light delivery over extended time periods enhances the effectiveness of photodynamic therapy. Clin Cancer Res 14:2796–2805CrossRefPubMedPubMedCentral Seshadri M, Belinier DA, Vaughan LA, Spernyak JA, Mazurchuk R, Foster TH, Henderson BW (2008) Light delivery over extended time periods enhances the effectiveness of photodynamic therapy. Clin Cancer Res 14:2796–2805CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Henderson BW et al (2000) Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate. Cancer Res 60:525–529PubMed Henderson BW et al (2000) Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate. Cancer Res 60:525–529PubMed
22.
Zurück zum Zitat Henderson BW, Gollnick SO, Snyder JW, Busch TM, Kousis PC, Cheney RT, Morgan J (2004) Choice of oxygen-conserving treatment regimen determines the inflammatory response and outcome of photodynamic therapy of tumors. Cancer Res 64:2120–2126CrossRefPubMed Henderson BW, Gollnick SO, Snyder JW, Busch TM, Kousis PC, Cheney RT, Morgan J (2004) Choice of oxygen-conserving treatment regimen determines the inflammatory response and outcome of photodynamic therapy of tumors. Cancer Res 64:2120–2126CrossRefPubMed
23.
Zurück zum Zitat Richter AM, Cerruti-Sola S, Sternberg ED, Dolphin D, Levy JG (1990) Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice. J Photochem Photobiol B 5(2):231–244CrossRefPubMed Richter AM, Cerruti-Sola S, Sternberg ED, Dolphin D, Levy JG (1990) Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice. J Photochem Photobiol B 5(2):231–244CrossRefPubMed
24.
Zurück zum Zitat Gomer CJ, Rucker N, Banerjee A, Benedict WF (1983) Comparison of mutagenicity and induction of sister chromatid exchange in Chinese hamster cells exposed to hematoporphyrin derivative photoradiation, ionizing radiation, or ultraviolet radiation. Cancer Res 43:2622–2627PubMed Gomer CJ, Rucker N, Banerjee A, Benedict WF (1983) Comparison of mutagenicity and induction of sister chromatid exchange in Chinese hamster cells exposed to hematoporphyrin derivative photoradiation, ionizing radiation, or ultraviolet radiation. Cancer Res 43:2622–2627PubMed
25.
Zurück zum Zitat Cerman E, Cekic O (2015) Clinical use of photodynamic therapy in ocular tumors. Surv Ophthalmol 60:557–574CrossRefPubMed Cerman E, Cekic O (2015) Clinical use of photodynamic therapy in ocular tumors. Surv Ophthalmol 60:557–574CrossRefPubMed
26.
Zurück zum Zitat Kaliki S, Shields CL, Al-Dahmash SA, Mashayekhi A, Shields JA (2012) Photodynamic therapy for choroidal metastasis in 8 cases. Ophthalmology 119:1218–1222CrossRefPubMed Kaliki S, Shields CL, Al-Dahmash SA, Mashayekhi A, Shields JA (2012) Photodynamic therapy for choroidal metastasis in 8 cases. Ophthalmology 119:1218–1222CrossRefPubMed
27.
Zurück zum Zitat Hussain RN, Jmor F, Damato B, Heimann H (2015) Verteporfin photodynamic therapy for the treatment of retinal vasoproliferative tumors. Ophthalmology 122:2361–2363CrossRefPubMed Hussain RN, Jmor F, Damato B, Heimann H (2015) Verteporfin photodynamic therapy for the treatment of retinal vasoproliferative tumors. Ophthalmology 122:2361–2363CrossRefPubMed
28.
Zurück zum Zitat Giansanti F, Virgili G, Varano M et al (2005) Photodynamic therapy for choroidal neovascularization in pediatric patients. Retina 25:590–596CrossRefPubMed Giansanti F, Virgili G, Varano M et al (2005) Photodynamic therapy for choroidal neovascularization in pediatric patients. Retina 25:590–596CrossRefPubMed
29.
Zurück zum Zitat Varano M, Iacono P, Giorno P, Chiaravalloti A, Parravano M (2014) Photodynamic therapy in subfoveal and juxtafoveal myopic choroidal neovascularization: a 10-year retrospective analysis. Ophthalmologica 231:204–210CrossRefPubMed Varano M, Iacono P, Giorno P, Chiaravalloti A, Parravano M (2014) Photodynamic therapy in subfoveal and juxtafoveal myopic choroidal neovascularization: a 10-year retrospective analysis. Ophthalmologica 231:204–210CrossRefPubMed
30.
Zurück zum Zitat Yildirim C, Cetin EN, Yayla K, Avunduk AM, Yaylali V (2011) Photodynamic therapy for unilateral idiopathic peripapillary choroidal neovascularization in a child. Int Ophthalmol 31:333–335CrossRefPubMed Yildirim C, Cetin EN, Yayla K, Avunduk AM, Yaylali V (2011) Photodynamic therapy for unilateral idiopathic peripapillary choroidal neovascularization in a child. Int Ophthalmol 31:333–335CrossRefPubMed
31.
Zurück zum Zitat Chuang L, Hwang Y, Wang N et al (2014) The chorioretinal damage caused by different half parameters of photodynamic therapy in rabbits. J Ocul Pharmacol Ther 30(8):642–649CrossRefPubMedPubMedCentral Chuang L, Hwang Y, Wang N et al (2014) The chorioretinal damage caused by different half parameters of photodynamic therapy in rabbits. J Ocul Pharmacol Ther 30(8):642–649CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Framme C, Flucke B, Birngruber R (2004) Comparison of reduced and standard light application in photodynamic therapy of the eye in two rabbit models. Graefes Arch Clin Exp Ophthalmol 244(7):773–781CrossRef Framme C, Flucke B, Birngruber R (2004) Comparison of reduced and standard light application in photodynamic therapy of the eye in two rabbit models. Graefes Arch Clin Exp Ophthalmol 244(7):773–781CrossRef
33.
Zurück zum Zitat Kang SJ, Grossniklaus HE (2011) Rabbit model of retinoblastoma. J Biomed Biotechnol 2011:1–5CrossRef Kang SJ, Grossniklaus HE (2011) Rabbit model of retinoblastoma. J Biomed Biotechnol 2011:1–5CrossRef
Metadaten
Titel
Rabbit model of ocular indirect photodynamic therapy using a retinoblastoma xenograft
verfasst von
Jonathan W. Kim
Bradley Jacobsen
Emily Zolfaghari
Angela Ferrario
Patricia Chevez-Barrios
Jesse L. Berry
Diana K. Lee
Grecia Rico
Ingy Madi
Narsing Rao
Kevin Stachelek
Lei-chi Wang
Charles Gomer
Publikationsdatum
02.10.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 12/2017
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-017-3805-8

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