Judith M. Megaw

Further Studies on Allopurinol Therapy and Human Cataractogenesis

We examined 11 cataractous lenses (or aspirated lens matter from extracapsular extractions) from patients ranging in age from 55 to 84 years who used allopurinol on a long-term basis (more than two years). Phosphorescence analyses demonstrated the characteristic allopurinol triplet in these lenses. When we analyzed normal lenses from patients taking allopurinol in a similar manner we found no evidence of allopurinol photobinding. These data indicated that allopurinol has a cataractogenic action only in patients in whom the drug has become photobound within the lens. Long-term allopurinol therapy does not necessarily cause or enhance cataracts in all patients. There may be a relationship between ultraviolet radiation exposure and circulating allopurinol levels (and perhaps renal function) in the genesis of photosensitized allopurinol cataracts.

Allopurinol Therapy and Cataractogenesis in Humans

Long-term ingestion of allopurinol, an antihyperuricemic agent used to treat gout, may be related to the development of lens opacities in relatively young patients (second to fifth decades of life). Cataracts obtained from three patients taking allopurinol were subjected to high-resolution phosphorescence spectroscopy. The characteristic allopurinol triplet was demonstrated in all three cataracts. Identical spectra were obtained for normal human lenses incubated in media containing 10(-3)M allopurinol and exposed to 1.2 mW/cm2 ultraviolet radiation for 16 hours; control lenses (irradiated without allopurinol) showed no allopurinol triplets. Similar data were obtained for lenses from rats given one dose of allopurinol and exposed to ultraviolet radiation overnight. These data provide evidence that allopurinol can be photobound in rat and human lenses and suggest its cataractogenic potential.

Gluthathione and ocular photobiology

Glutathione is present in both the reduced and oxidized form in the cornea, aqueous humor, ocular lens and retina. In these tissues it serves a variety of functions including maintaining normal tissue hydration (in the cornea) detoxifying peroxides and electrophilic compounds via enzymatic pathways and acting as a free radical scavenger to protect against photoinduced damage. In the ocular lens, glutathione levels decrease with aging and cataract formation. Recent evidence which may account in part for this phenomenon suggests that glutathione is altered when subjected to UV radiation in the presence of H2O2. Analyses employing fluorescence, phosphorescence, UV absorption and proton mode NMR spectroscopy demonstrate that UV exposure does alter both the reduced and oxidized forms of glutathione, producing the same final products. Moreover, while H2O2 speeds up the process, it is not essential to the reaction.

Glycoprotein synthesized by cultured cells: effects of serum concentrations and buffers on sugar content.

Summary A cell line derived from a murine teratocarcinoma was cultured in growth medium supplemented with either 10% or 1% fetal bovine serum or was grown in chemically-defined medium buffered with either a combination of HEPES and sodium bicarbonate or with bicarbonate alone. The sugar content of a particular glycoprotein secreted by these cells was markedly different in each case. No differences were noted in antigenicity or amino acid composition, including amino and carboxyl terminal amino acids. Differences in molecular weight were attributable to the difference in carbohydrate content. These data indicate that the level of glycosylation of proteins in vitro is dependent on the medium composition, including apparently unsuspected components such as buffers.

Further Studies on the Effects of UV Radiation on the Human Lens

Young (1st decade) and old (7th decade) normal human lenses were exposed to low-level (less than 1 mW/cm2) broadband UV radiation (300-400 nm). UV-induced effects in the whole lens and the extracted lens proteins were monitored by fluorescence spectroscopy. The lens proteins were also subjected to proton and pulse magnetization NMR spectroscopy. These studies provide further evidence that low-level UV radiation exposure enhances nontryptophan fluorescence and may generate additional (longer wavelength) chromophores. The NMR studies suggest that the young gamma crystallin fraction is particularly sensitive to UV radiation compared with the other crystallins.

PHOTOBIOLOGY: AN OVERVIEW

AbstractWithout the sun, life as we know it could not exist on earth. Solar energy (electromagnetic radiation) provides both the warmth required to make the planet habitable and the primary energy source for living organisms. How solar energy might influence and interact with living things has been of interest since ancient times. Today, the influences and interactions of nonionizing electromagnetic radiation, both from the sun and man-made sources, on biological systems, and the use of such radiation to study biological processes constitute the purview of the science of photobiology. Areas of interest falling under this general heading include vision, photosynthesis, environmental photobiology, bioluminescence, photomedicine, and others.

Prevention of Direct and Photosensitized Ultraviolet Radiation Damage to the Ocular Lens

Exposure to ambient ultraviolet (UV) radiation (longer than 300 nm) over a lifetime appears to play a role in lens aging and nuclear cataract formation. The photochemical generation of fluorescent chromophores has been correlated with the increasing yellow to brown color of the aging lens nucleus and with polypeptide chain cross-linking progressively increasing the insoluble protein level. Acute exposure to 300 nm radiation has also been implicated in human, as well as in animal cortical cataracts. These cortical cataracts develop after rat lenses are exposed to 300 nm UV radiation at irradiance levels of 26 J or more. The Spectra-Shield® lens can be used as a UV filter and will completely prevent the generation of fluorescent compounds within the lens as well as the UV cortical cataracts. The Spectra-Shield lens also prevents the formation of 8-methoxypsoralen (8-MOP) protein photoreac-tion products in UV-exposed rat lenses derived from animals given a single dose of 8-MOP. Furthermore, the Spectra-Shield lens fully retains its ability to reflect all UV radiation after continuous exposure to over 2,500 J of 300 nm UV radiation.

Common Antigens of Herpes Simplex Virus 2, Associated Hamster Tumors, and Human Cervical Cancer

Summary Using the immunodiffusion-adsorption-in-gel and/or the passive hemagglutination techniques, an antigenic relationship has been found between Herpes simplex virus type 2 (HSV-2), cervical cancer tissue antigen preparations, a cell culture derived from cervical cancer, and two HSV-2 associated hamster sarcomas. No cross-reactive antigens were detected between HSV-1, and the HSV-2 related hamster sarcomas or with human cervical cancer.

Transmission Characteristics of Commercially Available Sun Glasses

AbstractAlthough UVB radiation has been known to be the cause of certain adverse photoeffects for some time, UVA wavelengths of radiation have begun to be implicated in photodamage through the 1970s. The human lens is an effective filter for both UVB and W A radiation under normal conditions, but often needs additional support for this function in certain therapeutic or clinical situations. While ordinary glass is an effective filter of UVB radiation, it is a particularly good transmitter of UVA wavelengths. Commercially available sunglasses are thought to be able to filter out the UVA wavelengths not filtered by ordinary glass, thus giving full protection to the wearer. The authors examined the transmission characteristics of certain commercially available sunglasses spectrophotometrically, comparing their results to both quartz and plano glass lenses. A large variation in W A absorption in commercially available sunglasses was observed. The data corroborate previous research which indicates commercially...

Ocular and Cutaneous Manifestations of Puva Therapy — A Review

AbstractThe consequences of cumulative photochemical damage to the lens of the eye is described as a function of the increasing absorption of ultraviolet (UV) radiation, which produces photochemically generated lens chromophores. These increase in concentration and number as the lens ages. Two such chromophores are photodynamically characterized. This finding correlates with photobiological damage due to the accumulation of certain drugs within this organ, particularly 8-MOP in PUVA therapy patients. So-called PUVA cataracts are described and photographed with a newly described slit-lamp densitographic apparatus by comparing a PUVA patient prior to the institution of eye protection during therapy, against photographs of a normal eye. The authors also describe their own biopsy