During the last decade psoralens have become increasingly popular in treating psoriasis. The well-known photosensitizing action of these drugs has led to increasing concern regarding potential ocular complications, particularly in patients receiving prolonged psoralen therapy. We have demonstrated that this drug can be found in lenses of rats injected (intraperitoneally) with 4-8 mg/kg of 8-methoxypsoralen (8-MOP) and that its presence can lead to a photosensitized enhancement of lenticular fluorescence. Our experiments suggest one mechanism regarding the photosensitizing properties of 8-MOP within the ocular lens. Photo-addition products are generated with certain amino acid residues in the lens proteins which may result in the permanent retention of this compound within the ocular lens. We have recently shown that free 8-MOP can also be detected in human lenses for at least 12 hr following oral ingestion. Since the free 8-MOP tends to diffuse out of the lens during this period of time (as long as photic stimulation is prevented) it may be possible to prevent these photochemical reactions if the patient avoid exposure to ambient light for 12-24 hr immediately following ingestion of the drug. It may also be possible to protect these patients with special glasses which are capable of reflecting all UV radiation (up to 400 nm) while completely transmitting the visible radiation (400-750 nm).

Abstract— We have previously demonstrated that 8‐methoxypsoralen (8‐MOP) can be found in the lenses of rats injected (i.p.) with this drug, and that its presence can lead to a photosensitized enhancement of lenticular fluorescence. The cutaneous photosensitizing properties of psoralens are thought to be mediated via their excited triplet states, resulting in photoaddition cyclobutane products between pyri‐midine bases and 8‐MOP. We have now investigated the possibility that similar types of photoadducts could be generated between 8‐MOP and the aromatic amino acid residues in lens proteins. Our experiments involved in vitro irradiation (at 360 nm) of aqueous solutions of 0.1 mM 8‐MOP plus purified alpha, beta, or gamma crystallins from calf or normal human (under 20 years of age) lenses. UV absorption and fluorescence emission spectra were measured before and after radiation, and aliquots from all experiments were frozen and kept in the dark for subsequent phosphorescence and EPR spectroscopy. Similar experiments were performed with irradiated aqueous solutions of tryptophan or thymine plus 8‐MOP. All controls consisted of solutions kept in the dark. NMR spectra demonstrated that the hydrogen atoms at the 3,4 and 4',5' positions of the 8‐MOP molecule were lost following irradiation, suggesting that these two sites were involved in the photoproduct formed between tryptophan and 8‐MOP. These studies strongly suggest that 8‐MOP is capable of forming photoaddition products with tryptophan and with lens proteins as well as DNA in vivo, resulting in its permanent retention within the ocular lens.

(Priest et al., 1977). In addition, cultures for fluorescent antibody studies were grown in tissue culture slide chambers (Lab-Tek Products).

Young (1st decade) and old (7th decade) normal human lenses were exposed to low-level ( < 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.