Why is rose bengal more phototoxic to fibroblasts in vitro than in vivo?. Yao, M., Gu, C., Doyle, F. J., Zhu, H., Redmond, R. W., & Kochevar, I. E. Photochemistry and Photobiology, 90(2):297--305, April, 2014. 00005
doi  abstract   bibtex   
Photosensitized protein cross-linking has been recently developed to seal wounds and strengthen tissue. Although the photosensitizing dye, Rose Bengal (RB), is phototoxic to cultured cells, cytotoxicity does not accompany RB-photosensitized tissue repair in vivo. We investigated whether the environment surrounding cells in tissue or the high irradiances used for photo-cross-linking inhibited RB phototoxicity. Fibroblasts (FB) grown within collagen gels to mimic a tissue environment and monolayer cultured FB were treated with RB (0.01-1 mm) and the high 532 nm laser irradiances used in vivo for tissue repair (0.10-0.50 W cm(-2)). Monolayer FB were substantially more sensitive to RB photosensitization: the LD50 was \textgreater200-fold lower than that in collagen gels. Collagen gel protection was associated with increased Akt phosphorylation, a prosurvival pathway. RB phototoxicity in collagen gels was 25-fold greater at low (0.030 W cm(-2)) that at high (0.50 W cm(-2)) irradiances. Oxygen depletion at high irradiance only partially accounted for the irradiance dependence of phototoxicity as replacing air with nitrogen only increased the LD50 by four-fold in monolayers. These results indicate that the lack of RB phototoxicity during in vivo tissue repair results from upregulation of prosurvival pathways in tissue cells, oxygen depletion and irradiance-dependent RB photochemistry.
@article{yao_why_2014,
	title = {Why is rose bengal more phototoxic to fibroblasts in vitro than in vivo?},
	volume = {90},
	issn = {1751-1097},
	doi = {10.1111/php.12215},
	abstract = {Photosensitized protein cross-linking has been recently developed to seal wounds and strengthen tissue. Although the photosensitizing dye, Rose Bengal (RB), is phototoxic to cultured cells, cytotoxicity does not accompany RB-photosensitized tissue repair in vivo. We investigated whether the environment surrounding cells in tissue or the high irradiances used for photo-cross-linking inhibited RB phototoxicity. Fibroblasts (FB) grown within collagen gels to mimic a tissue environment and monolayer cultured FB were treated with RB (0.01-1 mm) and the high 532 nm laser irradiances used in vivo for tissue repair (0.10-0.50 W cm(-2)). Monolayer FB were substantially more sensitive to RB photosensitization: the LD50 was {\textgreater}200-fold lower than that in collagen gels. Collagen gel protection was associated with increased Akt phosphorylation, a prosurvival pathway. RB phototoxicity in collagen gels was 25-fold greater at low (0.030 W cm(-2)) that at high (0.50 W cm(-2)) irradiances. Oxygen depletion at high irradiance only partially accounted for the irradiance dependence of phototoxicity as replacing air with nitrogen only increased the LD50 by four-fold in monolayers. These results indicate that the lack of RB phototoxicity during in vivo tissue repair results from upregulation of prosurvival pathways in tissue cells, oxygen depletion and irradiance-dependent RB photochemistry.},
	language = {eng},
	number = {2},
	journal = {Photochemistry and Photobiology},
	author = {Yao, Min and Gu, Chuan and Doyle, Francis J. and Zhu, Hong and Redmond, Robert W. and Kochevar, Irene E.},
	month = apr,
	year = {2014},
	pmid = {24266530},
	note = {00005 },
	keywords = {Cells, Cultured, Collagen, Fibroblasts, Humans, In Vitro Techniques, Light, Rose Bengal},
	pages = {297--305}
}

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