In vivo AND PHOTOPHYSICAL STUDIES ON PHOTOOXIDATIVE DAMAGE TO LENS PROTEINS AND THEIR PROTECTION BY RADIOPROTECTORS

Abstract

Photooxidation, whether initiated by an endogenous or exogenous sensitizer, is an important mechanism in light induced damage to the lens. One of the substrates for this damage is lens protein. A porphyrin sensitizer which binds to lens proteins [mesotetra(p-sulfonatophenyl) porphyrin (TPPS)] was found to photooxidize Skh-2 pigmented mice lens protein in vivo. Uroporphyrin, a model for a non-binding photosensitizer, did not induce photooxidative damage to the mouse lens. The radioprotector 3-amino-2-hydroxypropyl phosphorothioate (WR-77913) was investigated as an agent to retard or negate in vivo photooxidative damage to the lens. Intraperitoneal injections of WR-77913 prior to irradiation reduced the TPPS induced photodestruction of lens protein in Skh-2 pigmented mice. The mechanism of protection was also investigated. Thiols were found to quench both the triplet state of porphyrins and the reactive intermediate singlet oxygen on the order of 10(5) and 10(6) M-1 s-1 respectively. These are probably not fast enough to explain most of the protection afforded by thiols. An additional mechanism may be the accelerated photobleaching of porphyrins by thiols which protects tissue by reducing the absorptions due to the porphyrins.

Studies on Singlet Oxygen Formation and UVA Light-mediated Photobleaching of the Yellow Chromophores in Human Lenses

“…These sensitizers included ribo¯avin (Andley, Chapman and Chylack, 1985), Rose Bengal (Balasubramanian, Du and Zigler, 1990), porphyrins (Roberts et al, 1991) and either methylene blue or formylkynurenine (Mandal, Bose and Chakrabarti, 1986;Ichijima and Iwata, 1987), all of which are capable of producing singlet oxygen in response to UVR light. These were accurate models, in that crude protein preparations from aged lenses also produced singlet oxygen when irradiated with UVA light (Zigler and Goosey, 1981;Linetsky and Ortwerth, 1997).…”

Enhanced photodynamic efficacy towards melanoma cells by encapsulation of Pc4 in silica nanoparticles

“…Over the last decade, a substantial effort has been directed towards improving this treatment. We have previously developed a method of selective protection of normal tissues for the eye, bladder, and skin (Bedwell et al , 1991; Reme et al , 1991; Roberts et al , 1991; Roberts and Dillon, 1993; Roberts et al , 1994) while allowing PDT therapy to destroy tumors. There has also been continuous development of several new classes of photosensitizers that can be excited at wavelengths longer than 640 nm, which allows deeper penetration, greater tumor specificity, and less cutaneous photosensitivity than Photofrin (Ali and van Lier, 1999; Detty et al , 2004; Nyman and Hynninen, 2004; Wainwright, 2008).…”

Detection of Porphyrin Excited States in the Intact Bovine Lens

“…uroporphyrin, UP) that d o not bind to lens proteins show no increase in the lifetime of the triplet state in the presence of these proteins. These studies have implications to possible in vivo effects since w e recently demonstrated that TPPS but not UP can photooxidize lens proteins in vivo (Roberts et al, 1991). T h e following is a study to determine how the photophysics of sensitizers are modified in intact lenses.…”