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Alcohol and the Eye
Abstract
This chapter discusses the effect of alcohol on eye diseases. Although alcoholics and people using three drinks of alcoholic beverages per day have increased risk of cataract and aging diseases of the eye, moderate consumption of alcohol appears to reduce risk of these diseases. The risk of cataracts shows a J-shaped response to consumption of alcoholic beverages, typical of hormesis. These effects on aging diseases of the eye may be a proxy for aging in general, because several studies have shown that early cataract operations are predictive of premature death. The well-known association of oxidative damage with aging is consistent with numerous reports indicating that alcoholism or hard drinking are reported to cause similar oxidative damage. In the case of heavy alcohol use, the oxidative damage to the liver appears to be a major factor in liver necrosis and this oxidative stress is likely to cataract formation. Damage to mitochondria may be involved in the pathogenesis of both these disease processes. Studies suggest that, the plasma has increased antioxidant activity after one drink but becomes pro-oxidant after three drinks, consistent with the epidemiological observations of decreased risk for moderate drinking and increased risk after three drinks.
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In this chapter, we will review recent findings which implicate the hepoxilins as modulators of second messenger systems in the human neutrophil. We have shown that the hepoxilins affect calcium homeostasis in the cell and that they stimulate the release of arachidonic acid and diradylglycerol but not inositol phosphate indicating a mode of action for these 12-lipoxygenase metabolites that is independent of phospholipase C activation. In fact lipid analyses indicate that the phospholipid affected by the hepoxilins is phosphatidyl choline, and that this phospholipid is hydrolyzed by a phospholipase D. These findings indicate that the hepoxilins, which are formed by the platelet as well as the neutrophil, may affect neutrophil activation through a potential cell-cell interaction in the circulation or at pathologic sites to initiate or potentiate the inflammatory process.
A composite slit-lamp based system for the clinical classification and grading of cataract is described. Cataract features are classified morphologically, and individual features are graded by comparison with standard diagrams mounted adjacent to the slit-lamp. Attention has been paid to relevant aspects of measurement theory, with equal interval steps between the grades. The image degrading effect of the cataract is assessed using a 'resolution target projection ophthalmoscope'. The method may be used in conjunction with photographic and image analysing techniques.
1. A technique for isolating and perfusing the rabbit cornea is described, which allowed its thickness to be continuously measured under the microscope. The reversal of thickness of the cold-swollen cornea on perfusion with various solutions at 37 degrees C was studied.2. It was found that only a combination of adenosine and glutathione was able to reliably reverse the thickness to its normal value. This mechanism is sodium, bicarbonate, and oxygen dependent. Inhibitors of glycolysis or electron transport stop the reversal process.3. The findings are consistent with a need for an ATPase but are not capable of distinguishing among several possibilities for its regulation.
1. Fluid transport across rabbit corneal tissue has been investigated by observing the movement of fluid interfaces under the microscope, or by mounting the tissue between two chambers and observing the displacement of menisci within capillary tubes.2. In both cases, the endothelial layer supported on a thin sheet of connective tissue is capable of pumping fluid in a direction out of the cornea, against a head of pressure. The volume of fluid moved may amount to twelve times the thickness of the endothelial cells in an hour.3. This active fluid movement accounts for the prevention of swelling of the normal corneal stroma. The hypothesis that corneal hydration is regulated by the sodium pump in the epithelial layer is not supported by these experiments.
Abstract– The present communication surveys the present knowledge about the extent to which formation of free radicals in the central nervous system may give rise to cross-linking reactions finally ending in the deposition of lipofuscin pigments.
Free radicals may be formed by autoperoxidation of polyunsaturated fatty acids. These fatty acids, e.g., C22:6ω3, are enriched in rods and cones of the eye and in phosphatidyl ethanolamine of synaptosomes. By peroxidation, malondialdehyde is formed. This aldehyde may cross-link through amino groups of proteins and certain phospholipids. Hereby, lipofuscin is deposited. The peroxidation process is counteracted by certain enzymic systems and by antioxidants. Thus, glutathionperoxidase (GSH-Px), catalase and superoxid dismutase may eliminate peroxides. GSH-Px is a selenium-containing enzyme. Peroxides are also formed by metabolic transformation of dopamine.
3 demential syndromes, i.e. Alzheimer's, Parkinson's and Batten's diseases, are discussed with regard to whether the “free radical theory” may explain the pathogenesis.
Finally, it is discussed whether an antioxidative treatment including vitamins E and C as well as a supplement of selenium, e.g. sodiumselenite, may be a therapeutic alternative to other types of treatment of demential syndromes or a direct supplement to the L-DOPA treatment of Parkinson's disease.
Chronic ethanol consumption adversely affects the respiratory activity of rat liver mitochondria. It causes increased cellular production of oxygen radical species and selectively decreases mitochondrial glutathione (GSH) levels. Here we show, using Southern hybridization techniques on total rat genomic DNA, that long-term (11-13 months) ethanol feeding, using the Lieber-DeCarli diet, results in a 36% (P <.05; n = 4) decrease in hepatic mitochondrial DNA (mtDNA) levels when compared with paired controls. UV quantitation of mtDNA isolated from hepatic mitochondria showed that chronic ethanol intake (11-13 months) causes a 44% (P <.01; n = 6) decrease in the amount of mtDNA per milligram of mitochondrial protein. No significant decline in mtDNA levels was seen in ethanol-fed animals maintained on the diet for 1 to 5 months. Ethanol feeding caused a 42% (P <.01; n = 4) and a 132% (P <.05; n = 3) increase in 8-hydroxydeoxyguanosine (8-OHdG) formation in mtDNA in animals maintained on the diet for 3 to 6 months and 10 to 11 months, respectively. In addition, agarose gel electrophoresis revealed a 49% increase (P <.05; n = 3) in mtDNA single-strand breaks (SSB) in animals fed ethanol for more than 1 year. These findings suggest that chronic ethanol consumption causes enhanced oxidative damage to mtDNA in older animals along with increased strand breakage, and that this results in its selective removal/degradation by mtDNA repair enzymes.
Cortical lens opacification has been associated with outdoor exposure and UV radiation more than other types of lens opacification. We studied risk factors for cortical lens opacification only, the most common as well as the earliest age related change we observe in the lens.
1,045 persons, 583 females and 462 males, 50 years and older, underwent a detailed eye examination and answered a questionnaire. Participants with cortical lens opacification grade I, totalling 374 persons, were assigned to case-control study I, and to case-control study II those with cortical lens opacification grades II and III, totalling 82 subjects. 378 age and sex matched persons served as controls.
Those who spent more than 4 hours/day outside on weekdays, in their 20's--30's and 40's--50's respectively, were found to have increased risk of moderate to severe cortical lens opacification. Thus the relative risk for grades II & III, was 2.80 (95% CI 1.01--7.80) and 2.91 (95% CI 1.13--9.62) respectively. Ageing and systemic cortical steroids use were also found to be risk factors.
Outdoor exposure appears to be associated with increased risk of moderate to severe cortical lens opacification. Ageing is, however, the main risk factor.
The Silences of the Archives, the Reknown of the Story.
The Martin Guerre affair has been told many times since Jean de Coras and Guillaume Lesueur published their stories in 1561. It is in many ways a perfect intrigue with uncanny resemblance, persuasive deception and a surprizing end when the two Martin stood face to face, memory to memory, before captivated judges and a guilty feeling Bertrande de Rols. The historian wanted to go beyond the known story in order to discover the world of the heroes. This research led to disappointments and surprizes as documents were discovered concerning the environment of Artigat’s inhabitants and bearing directly on the main characters thanks to notarial contracts. Along the way, study of the works of Coras and Lesueur took a new direction. Coming back to the affair a quarter century later did not result in finding new documents (some are perhaps still buried in Spanish archives), but by going back over her tracks, the historian could only be struck by the silences of the archives that refuse to reveal their secrets and, at the same time, by the possible openings they suggest, by the intuition that almost invisible threads link here and there characters and events.