Techniques to Improve Photodynamic Therapy.

Photodynamic therapy [dye-light therapy] is an excellent technique for use in detection and treatment of cancerous tissues. While this therapy is effective, it is limited by the phototoxic reactions that can occur in the surrounding normal tissues. These damaging side effects are of particular importance when treating neurosensory organs, such as the human eye.

The Photobiology of Lutein and Zeaxanthin in the Eye.

Lutein and zeaxanthin are antioxidants found in the human retina and macula. Recent clinical trials have determined that age- and diet-related loss of lutein and zeaxanthin enhances phototoxic damage to the human eye and that supplementation of these carotenoids has a protective effect against photoinduced damage to the lens and the retina. Two of the major mechanisms of protection offered by lutein and zeaxanthin against age-related blue light damage are the quenching of singlet oxygen and other reactive oxygen species and the absorption of blue light.

Time-resolved fluorescence studies of fullerene derivatives.

Fullerene (nano-C60) and its water-soluble derivatives have several clinical applications including use as a drug carrier to bypass the blood-ocular and blood-brain barriers. However, in vitro and in vivo detection of these nanomaterials is limited by their very low fluorescence quantum yield. The accumulation of fullerene and its derivatives in cells is particularly difficult to measure using standard fluorescence microscopy because their fluorescence is barely detectable in aqueous media.

Hypericin-mediated photooxidative damage of α-crystallin in human lens epithelial cells.

St. John's wort (Hypericum perforatum), a perennial herb native to Europe, is widely used for and seems to be effective in treatment of mild to moderate depression. Hypericin, a singlet oxygen-generating photosensitizer that absorbs in both the visible and the UVA range, is considered to be one of the bioactive ingredients of St.

Ultraviolet-A irradiation upregulated urokinase-type plasminogen activator in pterygium fibroblasts through ERK and JNK pathways.

Purpose: Effects of ultraviolet (UV) B on the pterygium and its cells have been studied previously, whereas little is known on the effects of UVA. Urokinase-type plasminogen activator (uPA) is a protease involved in tissue remodeling and cell migration, and its levels are increased in pterygium. The purpose of our study was to investigate the effects of UVA on the expression of uPA in cultured pterygium fibroblasts.

Effects of melatonin and its receptor antagonist on retinal pigment epithelial cells against hydrogen peroxide damage.

Purpose: Recently, we reported finding that circulating melatonin levels in age-related macular degeneration patients were significantly lower than those in age-matched controls. The purpose of this study was to investigate the hypothesis that melatonin deficiency may play a role in the oxidative damage of the retinal pigment epithelium (RPE) by testing the protective effect of melatonin and its receptor antagonist on RPE cells exposed to H(2)O(2) damage.

Methods: Cultured human RPE cells were subjected to oxidative stress induced by 0.

Phototoxicity of nano titanium dioxides in HaCaT keratinocytes--generation of reactive oxygen species and cell damage.

Nano-sized titanium dioxide (TiO(2)) is among the top five widely used nanomaterials for various applications. In this study, we determine the phototoxicity of TiO(2) nanoparticles (nano-TiO(2)) with different molecular sizes and crystal forms (anatase and rutile) in human skin keratinocytes under UVA irradiation. Our results show that all nano-TiO(2) particles caused phototoxicity, as determined by the MTS assay and by cell membrane damage measured by the lactate dehydrogenase (LDH) assay, both of which were UVA dose- and nano-TiO(2) dose-dependent.

Retinal photodamage by endogenous and xenobiotic agents.

The human eye is constantly exposed to sunlight and artificial lighting. Light transmission through the eye is fundamental to its unique biological functions of directing vision and circadian rhythm and therefore light absorbed by the eye must be benign. However, exposure to the very intense ambient radiation can pose a hazard particularly if the recipient is over 40 years of age.

In vitro phototoxicity and hazard identification of nano-scale titanium dioxide.

Titanium dioxide nanoparticles (nano-TiO(2)) catalyze reactions under UV radiation and are hypothesized to cause phototoxicity. A human-derived line of retinal pigment epithelial cells (ARPE-19) was treated with six samples of nano-TiO(2) and exposed to UVA radiation. The TiO(2) nanoparticles were independently characterized to have mean primary particle sizes and crystal structures of 22nm anatase/rutile, 25nm anatase, 31nm anatase/rutile, 59nm anatase/rutile, 142nm anatase, and 214nm rutile.

Immunological detection of N-formylkynurenine in porphyrin-mediated photooxided lens α-crystallin.

Crystallin proteins are responsible for maintaining lens transparency and allowing the lens to focus light undistorted onto the retina. The α-crystallins are the major lens crystallins, and function as both structural proteins and chaperones to protect all lens proteins from damage leading to lens deterioration. Because lens crystallin proteins do not turn over, the damage they accumulate can lead to cataracts, the world's leading cause of blindness.

Ultraviolet radiation as a risk factor for cataract and macular degeneration.

The human eye is constantly exposed to sunlight and artificial lighting. Light transmission through the eye is fundamental to its unique biological functions of directing vision and circadian rhythm, and therefore, light absorbed by the eye must be benign. However, exposure to the intense ambient radiation can pose a hazard particularly if the recipient is over 40 years of age.

Fullerol in human lens and retinal pigment epithelial cells: time domain fluorescence spectroscopy and imaging.

Fullerol is a fullerene derivative that is extensively hydroxylated [nano-C(60)(OH)(24)] and this makes it water-soluble. These fullerene derivatives have shown promise as drug carriers that bypass ocular barriers but fullerols are also potentially phototoxic to human lens and retinal tissues. Fluorescence imaging is a powerful and non-invasive means of probing nanoparticles in biological systems.

Detection and prevention of ocular phototoxicity of ciprofloxacin and other fluoroquinolone antibiotics.

Fluoroquinolone (FLQ) drugs are a potent family of antibiotics used to treat infections including ocular infections. To determine if these antibiotics may be phototoxic to the eye, we exposed human lens epithelial cells to 0.125-1 mm FLQs (ciprofloxacin [Cipro], lomefloxacin [Lome], norfloxacin [Nor] and ofloxacin [Ofl]), the precursor quinolone nalidixic acid (Nalid) and UVA radiation (2.

Comparison of A2E cytotoxicity and phototoxicity with all-trans-retinal in human retinal pigment epithelial cells.

All-trans-retinal is the precursor of A2E, a fluorophore within lipofuscin, which accumulates in human retinal pigment epithelial (hRPE) cells and contributes to age-related macular degeneration. Here we have compared the in vitro dark cytotoxicity and visible-light-mediated photoreactivity of all-trans-retinal and A2E in hRPE cells. All-trans-retinal caused distinct cytotoxicity in hRPE cells measured with cell metabolic activity (MTS) and lactate dehydrogenase release assays.

Phototoxicity and cytotoxicity of fullerol in human retinal pigment epithelial cells.

The water-soluble nanoparticle hydroxylated fullerene [fullerol, nano-C60(OH)(22-26)] has several clinical applications including use as a drug carrier to bypass the blood ocular barriers. We have previously found that fullerol is both cytotoxic and phototoxic to human lens epithelial cells (HLE B-3) and that the endogenous antioxidant lutein blocked some of this phototoxicity. In the present study we have found that fullerol induces cytotoxic and phototoxic damage to human retinal pigment epithelial cells.

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

Nanoparticles have been explored recently as an efficient means of delivering photosensitizers for cancer diagnosis and photodynamic therapy (PDT). Silicon phthalocyanine 4 (Pc4) is currently being clinically tested as a photosensitizer for PDT. Unfortunately, Pc4 aggregates in aqueous solutions, which dramatically reduces its PDT efficacy and therefore limits its clinical application.

Difference in phototoxicity of cyclodextrin complexed fullerene [(gamma-CyD)2/C60] and its aggregated derivatives toward human lens epithelial cells.

The water-soluble fullerene derivative gamma-cyclodextrin bicapped C(60) [(gamma-CyD)(2)/C(60), CDF0] has several clinical applications, including use as a drug carrier to bypass the blood ocular barriers or a photosensitizer to treat tumors in photodynamic therapy. We have assessed the potential ocular toxicity of (gamma-CyD)(2)/C(60) and its aggregated derivatives induced by UVA and visible light in vitro in human lens epithelial cells (HLE B-3). Cell viability using the MTS assay demonstrated that 2 microM (gamma-CyD)(2)/C(60) was highly phototoxic to HLE B-3 cells with UVA irradiation, while no effect was observed in the presence of visible light or when maintained in the dark.

Phototoxicity and cytotoxicity of fullerol in human lens epithelial cells.

The water-soluble, hydroxylated fullerene [fullerol, nano-C60(OH)22-26] has several clinical applications including use as a drug carrier to bypass the blood ocular barriers. We have assessed fullerol's potential ocular toxicity by measuring its cytotoxicity and phototoxicity induced by UVA and visible light in vitro with human lens epithelial cells (HLE B-3). Accumulation of nano-C60(OH)22-26 in the cells was confirmed spectrophotometrically at 405 nm and cell viability estimated using MTS and LDH assays.

Influence of dietary melatonin on photoreceptor survival in the rat retina: an ocular toxicity study.

Previous studies have shown that melatonin treatment increases the susceptibility of retinal photoreceptors to light-induced cell death. The purpose of this study was to evaluate under various conditions the potential toxicity of dietary melatonin on retinal photoreceptors. Male and female Fischer 344 (non-pigmented) and Long-Evans (pigmented) rats were treated with daily single doses of melatonin by gavage for a period of 14 days early in the light period or early in the dark period.

Phototoxicity in human retinal pigment epithelial cells promoted by hypericin, a component of St. John's wort.

St. John's wort (SJW), an over-the-counter antidepressant, contains hypericin, which absorbs light in the UV and visible ranges. In vivo studies have determined that hypericin is phototoxic to skin and our previous in vitro studies with lens tissues have determined that it is potentially phototoxic to the human lens.

Pulse radiolysis and steady-state analyses of the reaction between hydroethidine and superoxide and other oxidants.

Hydroethidine (HE) is a cell-permeable probe used for the intracellular detection of superoxide. Here, we report the direct measurement of the rate constant between hydroethidine and superoxide radical anion using the pulse radiolysis technique. This reaction rate constant was calculated to be ca.

Simulated microgravity induced damage in human retinal pigment epithelial cells.

Purpose: The goal of this study was to determine the potential damage to the human retina that may occur from weightlessness during space flight using simulated microgravity.

Methods: Human retinal pigment epithelial (hRPE) cells were cultured for 24 h in a National Aeronautics and Space Administration-designed rotating wall bioreactor vessel to mimic the microgravity environment of space. Single-stranded breaks in hRPE DNA induced by simulated gravity were measured using the comet assay.

Spectroscopic properties and reactivity of free radical forms of A2E.

A pyridinium bisretinoid (A2E) is the only identified blue-absorbing chromophore of retinal lipofuscin that has been linked to its aerobic photoreactivity and phototoxicity. Pulse radiolysis has been used to study both the one-electron oxidation and the one-electron reduction of A2E in aqueous micellar solutions. The reduction to the semireduced A2E (lambda(max) broad and between 500 and 540 nm) was achieved with formate radicals and the subsequent decay of A2E* was slow (over hundreds of milliseconds) via complex kinetics.