Ultraviolet radiation oxidative stress affects eye health

In the eye, ultraviolet radiation (UVR) is not known to contribute to visual perception but to mainly damage multiple structures. UVR carries higher energy than visible light and high dose exposure to UVR causes direct cellular damage, which has an important role in the development of cancer. This review provides an overview on the most recent knowledge on the role of UVR in oxidative stress (OS) in relation to noncancer ocular pathologies: various corneal pathologies, cataract, glaucoma and age‐related macular degeneration. Possible OS signaling streams and mechanisms in the aging eye are discussed. Excessive exposure to UVR through live may seriously contribute to increase in OS of various eye tissues and thus lead to the advancement of serious ocular pathologies. Children are especially vulnerable to UVR because of their larger pupils and more transparent ocular media: up to 80% of a person's lifetime exposure to UVR is reached before the age of 18. Therefore, efficient everyday protection of the sensitive tissues of the eye by wearing of sunglasses, clear UVR‐blocking spectacles or contact lenses should be considered from early age on. Many initiatives are taken worldwide to inform and raise the population's awareness about these possible UVR hazards to the eye.      

Characterization of Molecular Mechanisms of In vivo UVR Induced Cataract

Cataract is the leading cause of blindness in the world ¹. The World Health Organization defines cataract as a clouding of the lens of the eye which impedes the transfer of light. Cataract is a multi-factorial disease associated with diabetes, smoking, ultraviolet radiation (UVR), alcohol, ionizing radiation, steroids and hypertension. There is strong experimental ^2-4 and epidemiological evidence ^5,6 that UVR causes cataract. We developed an animal model for UVR B induced cataract in both anesthetized ⁷ and non-anesthetized animals ⁸.The only cure for cataract is surgery but this treatment is not accessible to all. It has been estimated that a delay of onset of cataract for 10 years could reduce the need for cataract surgery by 50% ⁹. To delay the incidence of cataract, it is needed to understand the mechanisms of cataract formation and find effective prevention strategies. Among the mechanisms for cataract development, apoptosis plays a crucial role in initiation of cataract in humans and animals ¹⁰. Our focus has recently been apoptosis in the lens as the mechanism for cataract development ^8,11,12. It is anticipated that a better understanding of the effect of UVR on the apoptosis pathway will provide possibilities for discovery of new pharmaceuticals to prevent cataract.In this article, we describe how cataract can be experimentally induced by in vivo exposure to UVR-B. Further RT-PCR and immunohistochemistry are presented as tools to study molecular mechanisms of UVR-B induced cataract.     

Argon laser irradiation of rabbits' eyes-changes in prostaglandin E2 levels

Laser irradiation of the eye is a widely used therapeutic measure in various ocular disorders. We investigated in laser-treated rabbits' eyes the changes in prostaglandin E2 (PGE2) levels of the tissue affected by the laser (the retina/choroid) and of its adjacent vitreous over a two-week period. The parameters studied were; PGE2 in vitro production by the retina/choroid, as well as PGE2 and protein levels in the vitreous, the latter indicative of a break in the blood retinal barrier (BRB). The effect of noncoherent light exposure used for illumination, and that of the mechanical manipulation involved (sham exposure) were also studied. Following laser exposure vitreal PGE2 levels were increased two-fold above baseline (days three and 14), whereas light exposure resulted in a single peak. PGE2 in vitro production by the retina/choroid in the laser-exposed group was elevated throughout the observation period, peaking twice (days 3 and 14), in the light-exposed group the enhanced production was evident during a shorter period, whereas in the sham group it remained unchanged from baseline. An elevation in vitreal protein levels to above baseline levels occurred in both the laser- and, to a lesser degree, in the noncoherent light-exposed groups, but not in the sham group. Our study demonstrated an enhanced PGE2 in vitro production by retina/choroid of laser-exposed eyes, which might be attributable to the additive effect of the laser induced trauma, and the noncoherent light photochemical changes; the clinical significance of the recurrent increase in vitreal PGE2 levels in laser-treated eyes might be related to its anti-inflammatory properties.     

A new model for laser-induced thermal damage in the retina

We describe a new model for laser-induced retinal damage. Our treatment is prompted by the failure of the traditional approach to accurately describe the image size dependence of laser-induced retinal injuries and by a recently reported study which demonstrated that laser injuries to the retina might not appear for up to 48 h post exposure. We propose that at threshold a short-duration, laser-induced, temperature rise melts the membrane of the melanosomes found in the pigmented retinal epithelial cells. This results in the generation of free radicals which initiate a slow chain reaction. If more than a critical number of radicals are generated then cell death may occur at a time much later than the return of the retina to body temperature. We show that the equations consequent upon this mechanism result in a good fit to the recent image size data although more detailed experimental data for rate constants of elementary reactions is still required. This paper contributes to the current understanding of damage mechanisms in the retina and may facilitate the development of new treatments to mitigate laser injuries to the eye. The work will also help minimize the need for further animal experimentation to set laser eye safety standards. Unemployed; no address available.     

Environmental light and endogenous antioxidants as the main determinants of non-cancer ocular diseases

The human eye is constantly exposed to sunlight and artificial lighting. Exogenous sources of reactive oxygen species (ROS) such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins contribute to oxidative damage in ocular tissues. Long-term exposure to these insults places the aging eye at considerable risk for pathological consequences of oxidative stress. Furthermore, in eye tissues, mitochondria are an important endogenous source of ROS. Over time, all ocular structures, from the tear film to the retina, undergo oxidative stress, and therefore, the antioxidant defenses of each tissue assume the role of a safeguard against degenerative ocular pathologies. The ocular surface and cornea protect the other ocular tissues and are significantly exposed to oxidative stress of environmental origin. Overwhelming of antioxidant defenses in these tissues clinically manifests as pathologies including pterygium, corneal dystrophies, and endothelial Fuch's dystrophy. The crystalline lens is highly susceptible to oxidative damage in aging because its cells and their intracellular proteins are not turned over or replaced, thus providing the basis for cataractogenesis. The trabecular meshwork, which is the anterior chamber tissue devoted to aqueous humor drainage, has a particular susceptibility to mitochondrial oxidative injury that affects its endothelium and leads to an intraocular pressure increase that marks the beginning of glaucoma. Photo-oxidative stress can cause acute or chronic retinal damage. The pathogenesis of age-related macular degeneration involves oxidative stress and death of the retinal pigment epithelium followed by death of the overlying photoreceptors. Accordingly, converging evidence indicates that mutagenic mechanisms of environmental and endogenous sources play a fundamental pathogenic role in degenerative eye diseases.     

Induced tolerance expressed as relaxed behavioural threat response in millimetre-sized aquatic organisms

Natural selection shapes behaviour in all organisms, but this is difficult to study in small, millimetre-sized, organisms. With novel labelling and tracking techniques, based on nanotechnology, we here show how behaviour in zooplankton (Daphnia magna) is affected by size, morphology and previous exposure to detrimental ultraviolet radiation (UVR). All individuals responded with immediate downward swimming to UVR exposure, but when released from the threat they rapidly returned to the surface. Large individuals swam faster and generally travelled longer distances than small individuals. Interestingly, individuals previously exposed to UVR (during several generations) showed a more relaxed response to UVR and travelled shorter total distances than those that were naive to UVR, suggesting induced tolerance to the threat. In addition, animals previously exposed to UVR also had smaller eyes than the naive ones, whereas UVR-protective melanin pigmentation of the animals was similar between populations. Finally, we show that smaller individuals have lower capacity to avoid UVR which could explain patterns in natural systems of lower migration amplitudes in small individuals. The ability to change behavioural patterns in response to a threat, in this case UVR, adds to our understanding of how organisms navigate in the ‘landscape of fear’, and this has important implications for individual fitness and for interaction strengths in biotic interactions.     

The effects on human health from stratospheric ozone depletion and its interactions with climate change.

Ozone depletion leads to an increase in the ultraviolet-B (UV-B) component (280-315 nm) of solar ultraviolet radiation (UVR) reaching the surface of the Earth with important consequences for human health. Solar UVR has many harmful and some beneficial effects on individuals and, in this review, information mainly published since the previous report in 2003 (F. R. de Gruijl, J. Longstreth, M. Norval, A. P. Cullen, H. Slaper, M. L. Kripke, Y. Takizawa and J. C. van der Leun, Photochem. Photobiol. Sci., 2003, 2, pp. 16-28) is discussed. The eye is exposed directly to sunlight and this can result in acute or long-term damage. Studying how UV-B interacts with the surface and internal structures of the eye has led to a further understanding of the location and pathogenesis of a number of ocular diseases, including pterygium and cataract. The skin is also exposed directly to solar UVR, and the development of skin cancer is the main adverse health outcome of excessive UVR exposure. Skin cancer is the most common form of malignancy amongst fair-skinned people, and its incidence has increased markedly in recent decades. Projections consistently indicate a further doubling in the next ten years. It is recognised that genetic factors in addition to those controlling pigment variation can modulate the response of an individual to UVR. Several of the genetic factors affecting susceptibility to the development of squamous cell carcinoma, basal cell carcinoma and melanoma have been identified. Exposure to solar UVR down-regulates immune responses, in the skin and systemically, by a combination of mechanisms including the generation of particularly potent subsets of T regulatory cells. Such immunosuppression is known to be a crucial factor in the generation of skin cancers. Apart from a detrimental effect on infections caused by some members of the herpesvirus and papillomavirus families, the impact of UV-induced immunosuppression on other microbial diseases and vaccination efficacy is not clear. One important beneficial effect of solar UV-B is its contribution to the cutaneous synthesis of vitamin D, recognised to be a crucial hormone for bone health and for other aspects of general health. There is accumulating evidence that UVR exposure, either directly or via stimulation of vitamin D production, has protective effects on the development of some autoimmune diseases, including multiple sclerosis and type 1 diabetes. Adequate vitamin D may also be protective for the development of several internal cancers and infections. Difficulties associated with balancing the positive effects of vitamin D with the negative effects of too much exposure to solar UV-B are considered. Various strategies that can be adopted by the individual to protect against excessive exposure of the eye or the skin to sunlight are suggested. Finally, possible interactions between ozone depletion and climate warming are outlined briefly, as well as how these might influence human behaviour with regard to sun exposure.     

Adverse effects of ultraviolet radiation: a brief review

Solar ultraviolet radiation (UVR) has always been part of the environment of man. UVB is required for the conversion of 7-deoxycholesterol to vitamin D, which is critically important in the maintenance of healthy bones and research is making clear that it has other potential roles in maintenance of human health. Exposure to UVR, whether of solar or artificial origin, also carries potential risks to human health. UVR is a known carcinogen and excessive exposure-at least to solar radiation in sunlight-increases risk of cancer of the lip, basal cell, and squamous cell carcinoma of the skin and cutaneous melanoma, particularly in fair skin populations. There is also evidence that solar UVR increases risk of several diseases of the eye, including cortical cataract, some conjunctival neoplasms, and perhaps ocular melanoma. Solar UVR may also be involved in autoimmune and viral diseases although more research is needed in these areas. Artificial UVR from tanning beds, welding torches, and other sources, may contribute to the burden of disease from UVR. This brief review will assess the human evidence for adverse health effects from solar and artificial UVR and will attempt to assign a degree of certainty to the major disease-exposure relationships based on the weight of available scientific evidence.     

SENSITIVITY OF ANTARCTIC UROSPORA PENICILLIFORMIS (ULOTRICHALES,CHLOROPHYTA) TO ULTRAVIOLET RADIATION IS LIFE‐STAGE DEPENDENT1

The sensitivity of different life stages of the eulittoral green alga Urospora penicilliformis (Roth) Aresch. to ultraviolet radiation (UVR) was examined in the laboratory. Gametophytic filaments and propagules (zoospores and gametes) released from filaments were separately exposed to different fluence of radiation treatments consisting of PAR (P = 400–700 nm), PAR + ultraviolet A (UVA) (PA, UVA = 320–400 nm), and PAR + UVA + ultraviolet B (UVB) (PAB, UVB = 280–320 nm). Photophysiological indices (ETR_max, E_k, and α) derived from rapid light curves were measured in controls, while photosynthetic efficiency and amount of DNA lesions in terms of cyclobutane pyrimidine dimers (CPDs) were measured after exposure to radiation treatments and after recovery in low PAR; pigments of propagules were quantified after exposure treatment only. The photosynthetic conversion efficiency (α) and photosynthetic capacity (rETR_max) were higher in gametophytes compared with the propagules. The propagules were slightly more sensitive to UVB‐induced DNA damage; however, both life stages of the eulittoral inhabiting turf alga were not severely affected by the negative impacts of UVR. Exposure to a maximum of 8 h UVR caused mild effects on the photochemical efficiency of PSII and induced minimal DNA lesions in both the gametophytes and propagules. Pigment concentrations were not significantly different between PAR‐exposed and PAR + UVR–exposed propagules. Our data showed that U. penicilliformis from the Antarctic is rather insensitive to the applied UVR. This amphi‐equatorial species possesses different protective mechanisms that can cope with high UVR in cold‐temperate waters of both hemispheres and in polar regions under conditions of increasing UVR as a consequence of further reduction of stratospheric ozone.     

Divergence in DNA photorepair efficiency among genotypes from contrasting UV radiation environments in nature

Populations of organisms routinely face abiotic selection pressures, and a central goal of evolutionary biology is to understand the mechanistic underpinnings of adaptive phenotypes. Ultraviolet radiation (UVR) is one of earth's most pervasive environmental stressors, potentially damaging DNA in any organism exposed to solar radiation. We explored mechanisms underlying differential survival following UVR exposure in genotypes of the water flea Daphnia melanica derived from natural ponds of differing UVR intensity. The UVR tolerance of a D. melanica genotype from a high‐UVR habitat depended on the presence of visible and UV‐A light wavelengths necessary for photoenzymatic repair of DNA damage, a repair pathway widely shared across the tree of life. We then measured the acquisition and repair of cyclobutane pyrimidine dimers, the primary form of UVR‐caused DNA damage, in D. melanica DNA following experimental UVR exposure. We demonstrate that genotypes from high‐UVR habitats repair DNA damage faster than genotypes from low‐UVR habitats in the presence of visible and UV‐A radiation necessary for photoenzymatic repair, but not in dark treatments. Because differences in repair rate only occurred in the presence of visible and UV‐A radiation, we conclude that differing rates of DNA repair, and therefore differential UVR tolerance, are a consequence of variation in photoenzymatic repair efficiency. We then rule out a simple gene expression hypothesis for the molecular basis of differing repair efficiency, as expression of the CPD photolyase gene photorepair did not differ among D. melanica lineages, in both the presence and absence of UVR.     

TEMPERATURE DEPENDENCE OF UV RADIATION EFFECTS ON ANTARCTIC CYANOBACTERIA

The mat-forming cyanobacterium Phormidium murrayi West and West isolated from a meltwater pond on the McMurdo Ice Shelf was grown in unialgal batch cultures to evaluate the temperature dependence of ultraviolet radiation (UVR) effects on pigment composition, growth rate, and photosynthetic characteristics. Chlorophyll a concentrations per unit biomass were generally reduced in cells grown under UVR (low UV-A plus UV-B). In vivo absorbance spectra showed that the carotenoid/chlorophyll a ratio increased as a function of photosynthetically available radiation (PAR) and UVR exposure and varied inversely with temperature. Ultraviolet inhibition of growth (percentage reduction of μ_max at each temperature) increased linearly with decreasing temperature, consistent with the hypothesis that net inhibition represents the balance between temperature-independent photochemical damage and temperature-dependent biosynthetic repair. There was no significant effect of UVR on photosynthesis over the first hour of exposure, but significant UV inhibition was observed after 5 days. Unlike growth, however, there was no apparent effect of temperature on the magnitude of UV inhibition of photosynthesis. These results imply that assays of UVR effects on photosynthesis are not an accurate guide to growth responses and that low ambient temperatures can have a major influence on the UV sensitivity of polar organisms. In a set of assays at 20° C (preacclimation under 300 μmol photons·m^?2·s^?1 and 20° C), growth was strongly depressed by UVR over the first day of exposure but then gradually increased over the subsequent 4 days, approaching the growth rates in the minus UVR control. This evidence of acquired tolerance indicates that the damaging effects of UVR will be most severe in environments where there is a mismatch between the timescale of change in exposure and the timescale of UV acclimation.     

Absence of ocular effects after either single or repeated exposure to 10 mW/cm(2) from a 60 GHz CW source

This study was designed to examine ocular effects associated with exposure to millimeter waves (60 GHz). Rabbits served as the primary experimental subjects. To confirm the results of the rabbit experiments in a higher species, the second phase of the study used nonhuman primates (Macaca mulatta). First, this study used time-resolved infrared radiometry to assess the field distribution patterns produced by different antennas operating at 60 GHz. These results allowed us to select an antenna that produced a uniform energy distribution and the best distance at which to expose our experimental subjects. The study then examined ocular changes after exposure at an incident power density of 10 mW/cm(2). Acute exposure of both rabbits and nonhuman primates consisted of a single 8 h exposure, and the repeated exposure protocol consisted of five separate 4 h exposures on consecutive days. One eye in each animal was exposed and the contralateral eye served as the sham-exposed control. After postexposure diagnostic examinations, animals were euthanized and the eyes were removed. Ocular tissue was examined by both light and transmission electron microscopy. Neither microscopic examinations nor the diagnostic procedures performed on the eyes of acute and repeatedly exposed rabbits found any ocular changes that could be attributed to millimeter-wave exposure at 10 mW/cm(2). Examination of the primates after comparable exposures also failed to detect any ocular changes due to exposure. On the basis of our results, we conclude that single or repeated exposure to 60 GHz CW radiation at 10 mW/cm(2) does not result in any detectable ocular damage.     

LASER SAFETY THRESHOLDS FOR CETACEANS AND PINNIPEDS

An increase in the use of oceanographic lidar has raised concern over laser safety for marine mammals. We were able to address some of these concerns by combining information about current laser safety standards, retinal damage mechanisms for humans, and research on eye anatomy for humans, cetaceans, and pinnipeds. To estimate the irradiance at the retina, the image size at the retina and pupil diameter must be known. We estimate the smallest spot size using retinal resolution or visual acuity for six species of cetaceans and five species of pinnipeds. A sensitivity ratio was calculated for each species using the ratio of the irradiance at the retina of the marine mammal to the irradiance at the retina of humans. The sensitivity ratio was used to suggest exposure limits for the various species. Because the human eye is more sensitive than either the cetacean or pinniped eye, we conclude that laser energies that are eye-safe for humans will also be safe for marine mammals, and higher laser irradiances may be permissible if illumination of humans is avoided.     

Recent advances in urocanic acid photochemistry, photobiology and photoimmunology.

Urocanic acid (UCA), produced in the upper layers of mammalian skin, is a major absorber of ultraviolet radiation (UVR). Originally thought to be a 'natural sunscreen', studies conducted a quarter of a century ago proposed that UCA may be a chromophore for the immunosuppression that follows exposure to UVR. With its intriguing photochemistry, its role in immunosuppression and skin cancer development, and skin barrier function, UCA continues to be the subject of intense research effort. This review summarises the photochemical, photobiological and photoimmunological findings regarding UCA, published since 1998.     

Fitness cost from fluctuating ultraviolet radiation in Daphnia magna

Solar ultraviolet radiation (UVR) is an important environmental threat for organisms in aquatic systems, but its temporally variable nature makes the understanding of its effects ambiguous. The aim of our study was to assess potential fitness costs associated with fluctuating UVR in the aquatic zooplankter Daphnia magna. We investigated individual survival, reproduction and behaviour when exposed to different UVR treatments. Individuals exposed to fluctuating UVR, resembling natural variations in cloud cover, had the lowest fitness (measured as the number of offspring produced during their lifespan). By contrast, individuals exposed to the same, but constant UVR dose had similar fitness to control individuals (not exposed to UVR), but they showed a significant reduction in daily movement. The re-occurring threat response to the fluctuating UVR treatment thus had strong fitness costs for D. magna, and we found no evidence for plastic behavioural responses when continually being exposed to UVR, despite the regular, predictable exposure schedule. In a broader context, our results imply that depending on how variable a stressor is in nature, populations may respond with alternative strategies, a framework that could promote rapid population differentiation and local adaptation.     

Protein misfolding and aggregation in cataract disease and prospects for prevention

The transparency of the eye lens depends on maintaining the native tertiary structures and solubility of the lens crystallin proteins over a lifetime. Cataract, the leading cause of blindness worldwide, is caused by protein aggregation within the protected lens environment. With age, covalent protein damage accumulates through pathways thought to include UV radiation, oxidation, deamidation, and truncations. Experiments suggest that the resulting protein destabilization leads to partially unfolded, aggregation-prone intermediates and the formation of insoluble, light-scattering protein aggregates. These aggregates either include or overwhelm the protein chaperone content of the lens. Here, we review the causes of cataract and nonsurgical methods being investigated to inhibit or delay cataract development, including natural product-based therapies, modulators of oxidation, and protein aggregation inhibitors.     

Mitochondrial oxidative stress-induced apoptosis and radioprotection in proton-irradiated rat retina

There is concern about possible radiation damage to the eyes from occupational exposure and medical procedures. In this study, molecular mechanisms of proton radiation-induced oxidative damage to retinal cells were evaluated, with and without a cell-permeable superoxide dismutase (SOD) mimetic, metalloporphyrin compound (MnTE-2-PyP). Retinal mitochondria-associated genes and protein expression profiles were studied. Rats were treated with MnTE-2-PyP at 2.5 μg/injection into one eye 1 h before irradiation. Proton irradiation was delivered to the same eye at doses of 1 or 4 Gy and assays were done at 6 h. Levels of Bax, Bcl-2 and Sod2 proteins were evaluated by Western blot and caspase-3 immunohistochemistry was performed to confirm the occurrence of apoptosis. Expression of several genes playing central roles in regulating the mitochondrial apoptotic pathway were significantly increased after radiation exposure, including Bbc3, Bax, Bak1, Bid, and Bcl2. Among genes involved in radiation-induced oxidative stress, Sod2, Gpx and Ucp3 were up-regulated, whereas Ucp2 was down-regulated. In addition, irradiation caused changes in various proteins involved in apoptosis (caspase-3, Bax and Bcl2). Reduction in pro-apoptotic and increase in anti-apoptotic protein levels were documented after treatment with MnTE-2-PyP. Decreased activity of cytochrome c, which is involved in initiation of mitochondrial apoptosis, was also revealed after irradiation and MnTE-2-PyP. Data demonstrated that proton radiation induced mitochondrial apoptosis and altered mitochondrial function in retina. MnTE-2-PyP protected, or at least ameliorated, radiation-induced oxidative damage. These insights prompt further study of this compound as a potential therapeutic candidate for retinal protection against degenerative ocular damage induced by ionizing radiation.