Featured Article: Inhibition of diabetic cataract by glucose tolerance factor extracted from yeast.

Diabetes leads to many complications; among them is the development of cataract. Hyperglycemia brings to increased polyol concentration in the lens, to glycation of lens proteins, and to elevated level of ROS (Reactive Oxygen Species) causing oxidative stress. The glucose tolerance factor (GTF) was found by several groups to decrease hyperglycemia and oxidative stress both in diabetic animals and humans. The aim of our study was to explore the damages induced by high glucose to the eye lens and to assess the protective effects of GTF both in vivo and in vitro The in vivo study included control healthy rats, streptozotocin (STZ) diabetic untreated rats, and STZ diabetic rats orally treated with 15 doses of GTF. The diabetic untreated rats developed cataracts, whereas the development of cataract was totally or partially prevented in GTF treated animals. In vitro studies were done on bovine lenses incubated for 14 days. Half of the lenses were incubated in normal glucose conditions, and half in high glucose conditions (450 mg%). To one group of the normal or high glucose condition GTF was added. The optical quality of all the lenses was measured daily by an automated scanning laser system. The control lenses, whether with or without GTF addition, did not show any reduction in their quality. High glucose conditions induced optical damage to the lenses. Addition of GTF to high glucose conditions prevented this damage. High glucose conditions affected the activity of aldose reductase and sodium potassium ATPase in lens epithelial cell. Addition of GTF decreased the destructive changes induced by high glucose conditions. The amount of soluble cortical lens proteins was decreased and structural changes were detected in lenses incubated in high glucose medium. These changes could be prevented when GTF was added to high glucose medium. Our findings demonstrate the anticataractogenic potential of GTF.

Simulation of heat exposure and damage to the eye lens in a neighborhood bakery.

Epidemiological studies indicated a link between high temperature environment and cataract. The purpose of the study was to investigate if the high temperature in neighborhood bakeries can cause damage to the eye lens. Measurements were done to determine the temperature and exposure time in the neighborhood bakeries during a workday. Thermal analysis was done using finite volume and finite element Computational Fluid Dynamics (CFD) codes in order to determine the temperature in the eye lens when exposed to environmental temperature fluctuations. A simulation of heat exposure was carried out using a bovine lens organ culture system. Two-hundred and seventy bovine lenses were divided into five groups. (1) Control group kept in culture for 11-14 days (2) Lenses exposed to 39.5 degrees C, 6h daily starting on the second day of the culture and kept in culture for 13 days (3) Lenses exposed to 39.5 degrees C, 4h daily starting on the second day of the culture and kept in culture for 11 days (4) Lenses exposed to 39.5 degrees C, 2h daily for 3 days starting on the second day of the culture and kept in culture for 12 days (5) Lenses exposed to 39.5 degrees C, 1h on the second day of the culture and kept in culture for 14 days. Lens optical quality was assessed during the culture period. At the end of the culture lens damage was demonstrated by inverted microscopy. Lens epithelial samples were taken for analysis of Catalase activities. Control lenses maintained their optical quality throughout the 14 days of the culture. Exposure to heat caused optical damage to the cultured lenses. The damage appeared earlier in the 6h exposure group and progressed from the lens anterior suture to its center. Optical damage was recovered in lenses exposed 1h to 39.5 degrees C, but the damage remained in the lens epithelial cells. Our study indicates that exposure to heat in bakeries can cause damage to the eye lens and that the damage is dependent on the length of exposure.

Non-thermal electromagnetic radiation damage to lens epithelium.

High frequency microwave electromagnetic radiation from mobile phones and other modern devices has the potential to damage eye tissues, but its effect on the lens epithelium is unknown at present. The objective of this study was to investigate the non-thermal effects of high frequency microwave electromagnetic radiation (1.1GHz, 2.22 mW) on the eye lens epithelium in situ. Bovine lenses were incubated in organ culture at 35°C for 10-15 days. A novel computer-controlled microwave source was used to investigate the effects of microwave radiation on the lenses. 58 lenses were used in this study. The lenses were divided into four groups: (1) Control lenses incubated in organ culture for 10 to15 days. (2) Electromagnetic radiation exposure group treated with 1.1 GHz, 2.22 mW microwave radiation for 90 cycles of 50 minutes irradiation followed by 10 minutes pause and cultured up to 10 days. (3) Electromagnetic radiation exposure group treated as group 2 with 192 cycles of radiation and cultured for 15 days. (4) Lenses exposed to 39.5°C for 2 hours 3 times with 24 hours interval after each treatment beginning on the second day of the culture and cultured for 11 days. During the culture period, lens optical quality was followed daily by a computer-operated scanning laser beam. At the end of the culture period, control and treated lenses were analyzed morphologically and by assessment of the lens epithelial ATPase activity. Exposure to 1.1 GHz, 2.22 mW microwaves caused a reversible decrease in lens optical quality accompanied by irreversible morphological and biochemical damage to the lens epithelial cell layer. The effect of the electromagnetic radiation on the lens epithelium was remarkably different from those of conductive heat. The results of this investigation showed that electromagnetic fields from microwave radiation have a negative impact on the eye lens. The lens damage by electromagnetic fields was distinctly different from that caused by conductive heat.

Desferrioxamine and zinc-desferrioxamine reduce lens oxidative damage.

Our purpose was to investigate the quality and morphology of cultured bovine lenses after exposure to hyperbaric oxygen (HBO) in the presence or absence of desferrioxamine (DFO) or zinc-desferrioxamine (Zn-DFO). Intact bovine lenses were cultured and exposed to HBO of 100% oxygen at 2.5 ATA for 120 min. One hundred and fifty lenses were included in the present study. Lenses were divided into study groups of 25 lenses each: (1a) HBO-exposed lenses; (1b) control lenses extracted from the contralateral eyes of group 1a and exposed to normal room air. (2a) HBO-exposed lenses treated with DFO; (2b) control lenses extracted from the contralateral eyes of group 2a exposed to normal room air in the presence of DFO (3a) HBO-exposed lenses treated with Zn-DFO; (3b) control lenses extracted from the contralateral eyes of group 3a, exposed to normal room air in the presence of Zn-DFO. Lens optical quality and structural changes were assessed. Oxygen toxicity to lenses was demonstrated by decreased light transmission, increase in focal length variability and a decrease in morphological integrity. Light intensity measurements showed a distinct pattern in control lenses. A different pattern was noticed for hyperbaric oxygen-exposed lenses. Focal length variability values were stable in control lenses and increased significantly in oxygen-exposed lenses. Structural damage to lenses was demonstrated by the appearance of bubbles between lens' fibers possibly demonstrating failure of lens tissue to cope with oxygen load. All measured parameters showed that both Zn-DFO and DFO attenuated the oxidative damage. The effect of DFO was small whereas Zn-DFO demonstrated a significantly stronger effect. Treatment of hyperbaric oxygen-exposed lenses with DFO only marginally reduced the oxidative damage. Treatment with Zn-DFO was superior in reducing the oxidative damage to lenses. These results indicate a possible role for Zn-DFO in the prevention of cataracts.

Zinc-desferrioxamine reduces damage to lenses exposed to hyperbaric oxygen and has an ameliorative effect on catalase and Na, K-ATPase activities.

Our purpose was to investigate the effects of exposure to high partial pressure of oxygen on lens optical quality and on the activities of lenticular catalase and Na, K-ATPase in culture and to examine the effect of zinc-desferrioxamine (Zn-DFO) addition to cultured lenses exposed to high oxygen partial pressure on these parameters. Bovine lenses, kept in organ culture, were exposed to different combinations of partial pressure of oxygen with and without addition of Zn-DFO complex (20 microM) and examined during a 14-day period. Lens optical quality, catalase, and Na, K-ATPase activity were compared between study and control groups. Two hundred lenses were included in the present study. Decreased lenticular optical quality and decreased catalase and Na, K-ATPase activities were observed in lenses exposed to hyperbaric oxygen. Lenses exposed to normobaric oxygen showed a reduction in these parameters to a lesser degree. The damaging optical and enzymatic effects of oxygen on lenses in culture increased in magnitude along the culture period. Addition of Zn-DFO to the culture just before the exposure to hyperbaric oxygen eliminated most of the optical and enzymatic oxygen-induced damage. Addition of Zn-DFO after the first exposure demonstrated reduction in the oxidative damage induced reduction of optical quality in a time-dependent manner - the later the addition of Zn-DFO took place the smaller the protective effect observed. High oxygen load has toxic effects on bovine lenses in organ culture conditions as determined by optical parameters as well as reduction of catalase and Na, K-ATPase activities. These toxic effects can be attenuated by introducing Zn-DFO just before lenses are exposed to oxygen. The beneficial effect of Zn-DFO, applied after lenses have been exposed to hyperbaric oxygen, on the oxidative damage was time-dependent - the earlier the application the more significant the observed protective effect. The present results may indicate a possible future role for Zn-DFO as a protective agent against oxygen-induced human cataract formation.

[Oxygen effect on ocular lens].

BACKGROUND: Cataract is the leading cause of preventable blindness worldwide. Clinical observations and laboratory results have shown that oxygen has a possible toxic role in cataract formation. AIM: The aim of the present study was to demonstrate, measure and characterize the damage caused to bovine lenses in organ culture as a result of their exposure to hyperbaric oxygen pressure. MATERIALS AND METHODS: Twenty bovine lenses exposed to hyperbaric pressure were compared to 20 control lenses. Lenses were kept in an organ culture for 14 days. Each day the focusing ability of the exposed lenses was compared to controls. The comparison was based on the amount to which the focus point of each measured ray diverged from the focus point of the lens. Lenses were also examined under the microscope and morphologic changes in study lenses were compared to controls. RESULTS: A statistically significant difference in focusing ability between the study and control lenses was observed. The difference became larger during the incubation period indicating an accumulation of damage. The damage resulted from the peripheral but not the central part of the lenses. The morphologic changes observed under the microscope matched the damage profile of the focusing ability. CONCLUSIONS: Oxygen has a possible role in cataract formation. The effect of oxygen is cumulative. The route of damage formation follows the diffusion of oxygen into the lens.

Effects of UV-A irradiation on lens morphology and optics.

Epidemiological studies have indicated that ultraviolet radiation (UVR) is one of the main factors leading to senile cataract formation. We investigated morphological changes in the eye lens caused by UVR-A. Twenty three pairs of lenses obtained from 23 one-year-old calves were used for this study. For each pair, one lens was exposed to 44 J/m(2) UVR in the 365 nm wavelength region while the contralateral lens was not exposed and served as a control. The lenses were placed in specially designed organ culture containers for pre-incubation. Lenses were exposed to UVR after one day in culture. After irradiation, lens optical quality was monitored throughout additional 15 days of the culture period and lenses were taken for morphological analysis by scanning electron microscopy. Damage to lens optical quality was evident as early as day 8 after the irradiation and increased with time in culture. We found irregularity of fiber morphology in lenses exposed to UV-A irradiation (but not in control lenses), similar to that reported previously for aged lenses. At the end of the culture period (day 16), lens fiber membranes also showed holes in fiber membranes. We conclude that UVR-A caused damage to cell membranes of the lens and alterations in lens optics, which may subsequently lead to senile cataract formation.

Long-term lens organ culture system to determine age-related effects of UV irradiation on the eye lens.

Aging of the eye lens represents the life-long accumulation of damage. Factors responsible for age-related cataract are unknown because medical evaluations of aged populations demonstrate a wide range of systemic diseases and medical disorders. There are some main suspected factors, which may contribute to accumulated age-related damage in the eye lens. (1) Diseases, such as diabetes, substantially increase the probability of cataract formation in the age group from 40 to 49, and double or triple this probability for ages 50 to 69. (2) Drugs, including systemic medications such as steroids. (3) Environmental factors, such as UV radiation, heat and electromagnetic radiation. Our study represents an effort to determine the effects of suspected cataractogenic factors on the eye lens. The experiments are performed using a unique long-term lens organ culture system of bovine lenses. In our system it is possible to give controlled amounts of insult and monitor changes in lens optical quality throughout the culture period of 8-15 days. The optical properties, monitored in association with biochemical analysis of lens epithelium, cortex and nuclear samples, help in determining the mechanisms of cataract formation. The present study investigates mechanisms by which UV-A radiation at 365 nm causes damage to the lens. It is believed that solar radiation is one of the major environmental factors involved in lens cataractogenesis. Bovine lenses were placed in our special culture cells for pre-incubation of 24 hr followed by irradiation of 29 or 33 J cm(-2). The lenses were maintained in the cells during irradiation. After irradiation, lens optical quality was monitored throughout the culture period and lens epithelium was taken for enzyme analysis. Using the culture system we learned that: (a) young lenses (less than one-year-old) are less sensitive to UV radiation than 3-year-old lenses; (b) the lenses have the ability to recover in organ culture conditions; (c) applying the insult in one step results in less damage than dividing the same insult in 4 steps with 24 hr interval between each one; and (d) the damage from UV is greater if the intervals between each irradiation stage are insufficient to permit full recovery.

Lenticular oxygen toxicity.

PURPOSE: To investigate the possible toxic effect of oxygen on lenses in an organ culture. METHODS: Bovine lenses were exposed to four different combinations of ambient pressure and oxygen concentration in an organ culture throughout a 7-day period. Lens transparency, histology, enzymatic activities, and photomicrographs were compared in study and control groups. RESULTS: No differences were observed between study and control lenses in all measured parameters in a group subjected to a single exposure of 100% oxygen under increased (i.e., hyperbaric) ambient conditions and a group exposed repeatedly to high ambient pressure and normal oxygen partial pressure. Decreased lenticular transparency and enzymatic activities along with structural changes were observed in lenses exposed repeatedly to 100% oxygen concentration under both normal and increased ambient pressures. The observed changes were oxygen-load-dependent: the higher the oxygen partial pressure and the longer the time of exposure, the more severe the changes observed. Optical and structural changes in the lens occurred in a centripetal orientation: the greater the oxygen load, the more central the damage. CONCLUSIONS: High oxygen load has a toxic effect on bovine lenses in organ culture. These effects appear to be cumulative: the higher the oxygen partial pressure and the greater the number of exposures, the more severe the changes observed in the lenses. Changes marking toxicity follow the route of oxygen diffusion into the lens, from the periphery to the center. Cautious interpretation of the results may indicate a role of oxygen (and/or its derivatives) in human cataract formation.