Acceleration of age-induced proteolysis in the guinea pig lens nucleus by in vivo exposure to hyperbaric oxygen: A mass spectrometry analysis.

Hyperbaric oxygen (HBO) treatment of animals or ocular lenses in culture recapitulates many molecular changes observed in human age-related nuclear cataract. The guinea pig HBO model has been one of the best examples of such treatment leading to dose-dependent development of lens nuclear opacities. In this study, complimentary mass spectrometry methods were employed to examine protein truncation after HBO treatment of aged guinea pigs. Quantitative liquid chromatography-mass spectrometry (LC-MS) analysis of the membrane fraction of guinea pig lenses showed statistically significant increases in aquaporin-0 (AQP0) C-terminal truncation, consistent with previous reports of accelerated loss of membrane and cytoskeletal proteins. In addition, imaging mass spectrometry (IMS) analysis spatially mapped the acceleration of age-related αA-crystallin truncation in the lens nucleus. The truncation sites in αA-crystallin closely match those observed in human lenses with age. Taken together, our results suggest that HBO accelerates the normal lens aging process and leads to nuclear cataract.

Healthy diets and the subsequent prevalence of nuclear cataract in women.

OBJECTIVE: To assess the association between healthy diet scores and prevalence of nuclear cataract in women. METHODS: The association between healthy diet scores, which reflect adherence to the US dietary guidelines, and prevalence of nuclear cataract determined 4 to 7 years later was assessed in a sample of Women's Health Initiative Observational Study participants (aged 50-79 years) residing in Iowa, Wisconsin, and Oregon. Scores on the 1995 Healthy Eating Index, which reflect adherence to 1990 guidelines, were assigned from responses to food frequency questionnaires at the Women's Health Initiative baseline (1994-1998). Presence of nuclear cataract was determined from slitlamp photographs and self-reports of cataract extractions were assessed from May 1, 2001, to January 31, 2004, in 1808 women participating in the Carotenoids in Age-Related Eye Disease Study. RESULTS: Having a high 1995 Healthy Eating Index score was the strongest modifiable predictor of low prevalence of nuclear cataract among numerous risk factors investigated in this sample. The multivariate-adjusted odds ratio for high vs low quintile for diet score was 0.63 (95% confidence interval, 0.43-0.91). Higher prevalence of nuclear cataract was also associated with other modifiable factors (smoking and marked obesity) and nonmodifiable factors (having brown eyes, myopia, and high pulse pressure). Vitamin supplement use was not related to cataract. CONCLUSION: These data add to the body of evidence suggesting that eating foods rich in a variety of vitamins and minerals may contribute to postponing the occurrence of the most common type of cataract in the United States.

Raman spectroscopic evidence for nuclear disulfide in isolated lenses of hyperbaric oxygen-treated guinea pigs.

Our laboratory treats guinea pigs with hyperbaric oxygen (HBO) as a model for investigating the formation of nuclear cataract. Previous analyses of lens supernatants using this model have shown an increase in disulfide (-SS-) and loss of sulfhydryl (-SH) in the lens nucleus of O(2)-treated animals. In this paper, we have used the non-invasive technique of Raman spectroscopy to confirm these findings in intact, freshly-excised lenses. Guinea pigs were treated 3 times per week with HBO for a total of 50 (4 months of treatment) or 85 (7 months of treatment) times to induce an increased level of lens nuclear light scattering. Intact lenses were analyzed by Raman spectroscopy using a 514.5 nm laser and collecting the scattered light in a 90 degrees geometry. The laser beam was focused either in the lens nucleus or equatorial cortex. Changes in the levels of -SS- (503 cm(-1)) and -SH (2577 cm(-1)) vibrations were measured. Raman spectra were analyzed by fitting Lorentzian profiles to the observed data in the -SS- and -SH regions. -SS- levels in the O(2)-treated nucleus were found to have increased by a factor of 2.1 (p=0.0001) and 2.5 (p=0.001) after 50 and 85 HBO treatments, respectively, compared to age-matched controls. Based on previous biochemical analyses, the -SS- increase was due mainly to the formation of protein disulfide (PSSP) with contribution also from protein/thiol mixed disulfides, but not from oxidized glutathione. -SH levels in the O(2)-treated nucleus decreased by 13% (p=0.007) and 35% (p=0.001) after 50 and 85 HBO treatments, respectively, compared to age-matched controls. No significant increase in -SS- or loss of -SH was observed in the lens cortex of the O(2)-treated guinea pigs. The Raman spectroscopy results rule out the possibility that artifactual production of -SS- and loss of -SH occurred during homogenization of lenses in previous studies. The data provide additional evidence to support a link between O(2), disulfide-crosslinking of lens crystallins in the nucleus, and nuclear cataract.

Risk factors for nuclear lens opacification: the Reykjavik Eye Study.

PURPOSE: The purpose of this study is to examine risk factors for nuclear lens opacification in citizens of Reykjavik. METHODS: 1,045 persons, 583 females and 462 males aged 50 years and older, were randomly sampled and underwent a detailed eye examination and answered a questionnaire. In all Scheimpflug photography of the anterior eye segment was done including the lens as well as retroilluminated photography of the lens. These photographs were used for the diagnosis of lens opacification. The data was analyzed using a logistic regression model. RESULTS: An increased risk for all grades of nuclear opacifications was found with ageing (OR = 1.228, 95% CI = 1.192-1.264, p = 0.000), cigarette smoking for more than 20 pack/years (OR = 2.521, 95% CI = 1.521-4.125, p = 0.000) and pipe or cigar smoking (OR = 2.478, 95% CI = 1.200-5.116, p = 0.014). Outdoor exposure, cortical lens opacification grade II and III and computer usage were not found to be linked to higher risk of nuclear opacification. No correlation was found between nuclear opacification and the consumption of vitamins, herring, sardines and shrimps, cod-liver oil or plant oil, nor were iris color, hyperopia, systemic steroid use, cardiovascular disease, diabetes, glaucoma and pseudoexfoliation found to have a significant effect. CONCLUSIONS: Ageing is a major risk factor for nuclear lens opacification, and smoking is a major modifiable risk factor. Cortical and nuclear lens opacifications do not share the same modifiable risk factors.

Attributable risk estimates for cataract to prioritize medical and public health action.

PURPOSE: Cataract is the most common cause of blindness in the world. The purpose of this study was to estimate the population attributable risk associated with identified risk factors for cortical, nuclear, and posterior subcapsular (PSC) cataract in a representative sample of the Victorian population aged 40 years and older. METHODS: Cluster, stratified sampling was used and participants were recruited through a household census. At locally established test sites, standardized clinical examinations were performed to assess cataract and personal interviews were conducted to quantify potential risk factors. Multivariate logistic regression was used to determine the independent risk factors associated with the three types of cataract, and the population attributable risk was calculated. RESULTS: A total of 3271 (83% of eligible) of the urban residents and 1473 (92%) rural residents participated. The urban residents ranged in age from 40 to 98 years (mean, 59 years), and 1511 (46%) were men. The rural residents ranged in age from 40 to 103 years (mean, 60 years), and 701 (48%) were men. The overall prevalence of cortical cataract was 12.1% (95% CL 10.5, 13.8), nuclear cataract 12.6% (95% CL 9.61, 15.7), and PSC cataract 4.93% (95% CL 3.68, 6.17). Significant risk factors for cortical cataract included age, female gender, diabetes for greater than 5 years, gout for greater than 20 years, arthritis, myopia, average annual ocular UV-B exposure, and family history of cataract (parents or siblings). Significant risk factors for nuclear cataract included age, female gender, rural residence, age-related maculopathy, diabetes for greater than 5 years, smoker for greater than 30 years, and myopia. The significant risk factors for PSC cataract were age, rural residence, thiazide diuretic use, and myopia. Of the modifiable risk factors, ocular UV-B exposure explains 10% of the cortical cataract in the community, and cigarette smoking accounts for 17% of the nuclear cataract. CONCLUSIONS: Because of the near universal exposure to UV-B in the environment, ocular protection has one of the highest modifiable attributable risks for cortical cataract and would therefore be an ideal target for public health intervention. Quit smoking campaigns can be expanded to incorporate information about the excess cataract in the community associated with long-term smoking. Nonmodifiable risk factors such as age, gender, and long-term medication use have implications for the timely referral and treatment for those at higher risk of cataract.

Nuclear vacuoles in nuclear cataract.

The human lens nucleus has always been described as a homogeneous part of the lens, and if any distinct opacities are found, these are considered to be congenital. However, in lenses with nuclear cataract, both of senile type and those induced by hyperbaric oxygen, we have found relatively transparent vacuoles in the nucleus of similar appearance as cortical vacuoles. In cataracts induced by hyperbaric oxygen the vacuoles were reversible to some extent. The vacuoles have been investigated with slit-lamp photography and quantitative microradiography. Nuclear vacuoles were found in 11 out of 25 patients treated with hyperbaric oxygen compared to 19 out of 100 pre-operatively examined senile nuclear cataracts. In the microradiographs the vacuoles appeared as dark rounded areas with a lower dry mass content (approximately 0.30 g X cm-3) than the surroundings (approximately 0.50 g X cm-3).

Histologic changes during selenite cataractogenesis: a light microscopy study.

The purpose of this research was to study the early histologic changes occurring in the lens during the formation of selenite overdose cataract. Fourteen-day-old rat pups received a single injection of 2.25 mg Se (kg body wt)-1. Lenses at each of three stages of cataract formation were observed biomicroscopically, and then 1-2 micron sections of methacrylate-embedded lenses were evaluated with the light microscope. The first observable change was vacuolization, which started at the lens bow and later spread throughout the posterior subcapsular region (Stage 1). This was followed by an abrupt increase in basophilia at the interface between the peripheral nucleus and cortex (Stage 2). Subsequent formation of nuclear opacity was characterized by the presence of opaque particles, abnormal basophilic structures, and lens fiber damage (Stage 3). The data were consistent with the hypothesis that an early site of attack of selenite is at or near the lens bow, and this leads to biochemical changes, fiber cell damage, impaired nutrient circulation, and formation of nuclear cataract.