UVA Light In vivo Reaches the Nucleus of the Guinea Pig Lens and Produces Deleterious, Oxidative Effects

Abstract

The possible role of ultraviolet light in the formation of cataract is not well understood. In this study, guinea pigs were exposed to a chronic, low level of UVA light (0.5 mWcm(-2), 340-410 nm wavelength, peak at 365 nm) for 4-5 months. It is known that the lens of the guinea pig possesses unusually high levels of the UVA chromophore NADPH. In a preliminary analysis, it was found that isolated guinea pig corneas transmitted 70-90% of 340-400 nm light, and that UVA radiation was able to penetrate deep into the nucleus of the guinea pig lens, where it was absorbed. Exposure of guinea pigs to UVA in vivo produced a 60% inactivation of lens epithelial catalase; however, analysis by transmission electron microscopy (TEM) showed no apparent morphological effects on either the lens epithelium or the cortex. A number of UVA-induced effects were found in the nucleus of the guinea pig lens, but were observed either not at all or to a lesser extent in the cortex. The effects included an increase in light scattering (two-fold; slit-lamp examination), distention of intercellular spaces (TEM), an increase in lipid peroxidation (30-35%; infrared spectroscopy), a decrease in GSH level (30%), an increase in protein-thiol mixed disulfide levels (80%), loss of water-soluble protein (20%), an increase in the amount of protein disulfide (two-fold; two-dimensional diagonal electrophoresis), degradation of MIP26 (15%) and loss of cytoskeletal proteins including actin, alpha- and beta- tubulin, vimentin and alpha-actinin (60-100%). The results indicate that a 4-5 month exposure of guinea pigs to a biologically relevant level of UVA light produces deleterious effects on the central region of the lenses of the animals. UVA radiation, coupled presumably with the photoreactive UVA chromophore NADPH and trace amounts of O(2) present in the lens nucleus, produced significant levels of oxidized products in the nuclear region over a five month period. The data demonstrate the potentially harmful nature of UVA light with respect to the lens, and highlight the importance of investigating a possible role for this type of radiation in the formation of human cataract.

Impact of iris pigment and pupil size in ultraviolet radiation cataract in rat

“…The low UVR-B penetration into the lens (Lo¨fgren & So¨derberg 2001) further argues against UVR-B-induced nuclear cataract. UV-A radiation on the other hand reaches the lens nucleus and is suggested as one cause for human nuclear cataract (Giblin et al 2002).…”

Inhibitory effects of (-)-epigallocatechin-3-gallate on melanogenesis in ultraviolet A-induced B16 murine melanoma cell

“…UVR induces the accumulation of reactive oxygen species (ROS) which stimulates the secretion of hormones such as α-melanocytestimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH), endothelin-1(ET-1), as well as basic fibroblast growth factor (bFGF), stem cell factor (SCF) and immune factors [2,3]. These induced factors stimulate the expression of microphthalmiaassociated transcription factor (MITF) by acting melanocortin receptor 1 (MC1R), endothelin receptor (EDNR) and stem cell growth factor receptor (SCFR) on the melanin cell membrane through the pathway of cyclic adenosine monophosphate protein kinase A (cAMP-PKA) or nitric oxide/cyclic guanylate monophosphate protein kinase G (NO/cGMP-PKG).…”

UVA Light-excited Kynurenines Oxidize Ascorbate and Modify Lens Proteins through the Formation of Advanced Glycation End Products

“…Godar et al (39) and Ortwerth et al (40) demonstrated that ϳ0.8 -1.1 mJ/cm 2 of UVA can reach the lens surface in the midday sun, but only 0.06 -0.08 mJ/cm 2 of UVB light reaches the lens under the same conditions (39,41,42). Dillon et al (42) demonstrated that, unlike UVB light, UVA light can penetrate the nucleus of the aged human lens, where most photooxidation has been observed (43,44).…”