TY - JOUR
T1 - Competitive quenching
T2 - A possible novel approach in protecting RPE cells from damage during PDT
AU - Weinberger, Dov
AU - Ron, Yonina
AU - Lusky, Moshe
AU - Gaaton, Dan
AU - Orenstein, Arie
AU - Blank, Michael
AU - Mandel, Mathilda
AU - Livnat, Tamar
AU - Barliya, Tilda
AU - Lavie, Gad
N1 - Funding Information:
This paper was supported by a grant from the Maratier Foundation for support of research in intraocular diseases.
PY - 2005/4
Y1 - 2005/4
N2 - Purpose: The purpose of this study is to demonstrate feasibility of using our novel concept, termed competitive quenching, for protecting the choroidal extravascular compartment and retinal pigment epithelium (RPE) from verteporfin (VP)-induced phototoxicity using hypericin. Furthermore, we aim to achieve partitioning of the quencher, hypericin, in the extravascular space and VP within the microvascular compartment of the chorio-retinal complex in vivo. Methods: We protect RPE cells from damage inflicted by photoactivated VP by introducing hypericin into these cells prior to photosensitization to quench the photosensitizing activity of VP. Cell protection levels were measured by MTT and Hemacolor viability assays. Wavelength range used for VP photoexcitation (700 ± 40 nm) excludes the absorption range of hypericin, preventing the latter from photoactivation. Pharmacokinetic conditions, in which hypericin spreads throughout the choroidal and retinal extravascular space while VP is confined to the vasculature, are delineated using double-fluorescence imaging. Results: Cell viability increased 3- to 5-fold when 10-20 μM hypericin were present in RPE cells during photosensitization with 0.1-0.5 μM VP. VP fluorescence intensity was unchanged by the presence of hypericin in the cells. Hypericin administered intravenously to rats was confined to the choroidal vasculature after 15 min to 2 hr. Subsequently, hypericin partitioned to the choroidal and retinal extravascular space. VP administered at this time was confined to the microvasculature. Conclusions: RPE and choroid may potentially be protected by compartmentalizing hypericin to the extravascular compartment while VP administered shortly before photosensitization is confined to the microvasculature. Adverse photodynamic therapy (PDT) damage to choroidal tissues adjacent to neovasculature targeted for photoablation have the potential of being prevented by competitive quenching with hypericin.
AB - Purpose: The purpose of this study is to demonstrate feasibility of using our novel concept, termed competitive quenching, for protecting the choroidal extravascular compartment and retinal pigment epithelium (RPE) from verteporfin (VP)-induced phototoxicity using hypericin. Furthermore, we aim to achieve partitioning of the quencher, hypericin, in the extravascular space and VP within the microvascular compartment of the chorio-retinal complex in vivo. Methods: We protect RPE cells from damage inflicted by photoactivated VP by introducing hypericin into these cells prior to photosensitization to quench the photosensitizing activity of VP. Cell protection levels were measured by MTT and Hemacolor viability assays. Wavelength range used for VP photoexcitation (700 ± 40 nm) excludes the absorption range of hypericin, preventing the latter from photoactivation. Pharmacokinetic conditions, in which hypericin spreads throughout the choroidal and retinal extravascular space while VP is confined to the vasculature, are delineated using double-fluorescence imaging. Results: Cell viability increased 3- to 5-fold when 10-20 μM hypericin were present in RPE cells during photosensitization with 0.1-0.5 μM VP. VP fluorescence intensity was unchanged by the presence of hypericin in the cells. Hypericin administered intravenously to rats was confined to the choroidal vasculature after 15 min to 2 hr. Subsequently, hypericin partitioned to the choroidal and retinal extravascular space. VP administered at this time was confined to the microvasculature. Conclusions: RPE and choroid may potentially be protected by compartmentalizing hypericin to the extravascular compartment while VP administered shortly before photosensitization is confined to the microvasculature. Adverse photodynamic therapy (PDT) damage to choroidal tissues adjacent to neovasculature targeted for photoablation have the potential of being prevented by competitive quenching with hypericin.
KW - AMD
KW - Choroidal neovascularization
KW - Hypericin
KW - Photodynamic therapy
KW - Verteporfin
UR - http://www.scopus.com/inward/record.url?scp=20444423820&partnerID=8YFLogxK
U2 - 10.1080/02713680590927597
DO - 10.1080/02713680590927597
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:20444423820
SN - 0271-3683
VL - 30
SP - 269
EP - 277
JO - Current Eye Research
JF - Current Eye Research
IS - 4
ER -
