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Biomedical subjects

O Hockwin

Publications and source records attributed to O Hockwin.

At least 109 records · Page 6Linked to original sources

Is it possible to maintain a normal glutathione level in lenses in vitro?

In most types of experimentally induced cataracts, glutathione (GSH) content decreases considerably before the onset of opacity. GSH may provide a protective function for protein SH groups by scavenging oxidative products that may impair lens metabolism. To avoid impairment of lens metabolism by decreased levels of GSH it may be possible in vitro: (1) to stimulate GSH synthesis by enrichment of the incubation medium with the amino acids necessary for GSH synthesis or (2) to enrich the incubation medium with the tripeptide itself so that it can be taken up by the lens. Both approaches were investigated with bovine lenses. Lenses were incubated in pairs in a salt solution without carbohydrates, so as to deplete lens of GSH. Following starvation, one lens of each pair was incubated for recovery in TCM 199 enriched with MgSO4 and the three amino acids of GSH; the other lens was put into a freshly prepared salt solution. After 6 h, lenses from the recovery solution contained more GSH than the other lenses. Addition of fructose-1,6-diphosphate to the medium enhanced this effect. When, after starvation, lenses were incubated in the presence of different amounts of GSH, GSH lens content rose, with the highest in those lenses incubated in a medium with a final molarity of 4 X 10(-3) M GSH. Therefore, incubation of lenses depleted of GSH in medium with either the amino acids of GSH or GSH itself appear to facilitate recovery of GSH content.

Animals↗

Measurement of anterior chamber diameter and biometry of anterior segment by Scheimpflug slitlamp photography.

Twenty-eight fresh donor eyes (Georgia Lions Eye Bank) ranging in age from four months to 87 years were used for an in vitro study to determine the feasibility of obtaining accurate anterior chamber diameter measurements with our Scheimpflug ultraviolet-visible slitlamp densitography apparatus. The in vivo study was performed on 16 hybrid monkeys (of varying age). These data were within 0.1 mm of measurements obtained with a modified paracentesis needle specially designed to obtain such measurements (sensitivity within 0.01 mm). The results of the foregoing study demonstrate that the Scheimpflug slitlamp photographic analyses can provide an accurate measurement of the anterior chamber diameter without entering the globe surgically. This will enable the surgeon to determine the diameter and order an anterior chamber IOL of a specified size prior to surgery. We have devised an automated program to analyze the negatives and provide direct anterior chamber diameter measurements.

Adult↗

[What possibilities exist to modify cataract development on the basis of current biochemical knowledge? Where can drugs act?].

During the last 10-15 years, investigations into the biology and biochemistry of the lens have demonstrated that the age changes observed cannot be the only cause of the formation of senile cataract. The various types of opacities and the wide age range in which they begin indicate a multifactorial origin involving endogenous and exogenous risk factors. Initial epidemiological studies have identified certain risk factors. Experimental cataract research is able to elucidate possible damaging mechanisms by using cataract models, for instance, the cataracts caused by excess carbohydrate (galactose, glucose), naphthalene application, ionizing rays, or by additional cocataractogenics, thus indicating steps for countermeasures. Taking (true) diabetic cataract of rats after Streptozotocin injection as an example, the efficacy of aldose reductase inhibitors is shown. Even if additional cataractogenic factors such as naphthalene and X-rays are applied, diabetic lens opacities can be prevented completely. Damage by naphthalene is due to an increased oxidative change in the lens protein. Several substances promoting the antioxidative capacity of the lens, thereby inhibiting cataract formation, are already available. Preclinical or clinical studies have demonstrated the efficacy of only a few of the commercially available anticataract drugs. The results of animal experiments presented here may well represent a basis for the development of really effective anticataract drugs.

Aging↗

Monitoring lens transparency during in vitro incubation by Scheimpflug photography and densitometric image analysis.

Dragomirescu et al. [1983] described a 2-chamber flow system for the incubation of lenses with an inserted photometer to measure changes in lens transparency. Mester et al. [1984] applied the method to simulate conditions occurring during vitrectomy, which occasionally leads to reversible lens opacification. Using Scheimpflug photography (a modified SL 45 Topcon camera) instead of the transmission measurements of incubated lenses has the advantage that disorders in lens transparency can be exactly localized and the sensitivity is much higher than the photometer readings. Application of Scheimpflug photography required a modification of the incubation chamber. The application of the experimental set-up was demonstrated with pig lenses under various incubation conditions. The results obtained by densitometric image analysis of Scheimpflug photos were compared with transmission measurements by photometer.

Animals↗

Comparison of aldose reductase inhibitors by determination of IC50 with bovine and rat lens extracts.

The inhibition constants of several aldose reductase inhibitors were determined using water-soluble extracts of bovine and rat lenses. The most potent inhibitor was the Alcon compound AL-1576; the inhibitory effects of AL-1567 and Sorbinil were about equal, but both were less effective than AL-1576, and the least effective inhibitor was the calcium antagonist verapamil. There was no general difference between inhibition constants for the inhibitors in question between bovine or rat extracts. Age of bovine lenses has no effect on the IC50 of the investigated aldose reductase inhibitor compounds.

Aldehyde Reductase↗

Long-term follow-up examination of experimental cataracts in rats by Scheimpflug photography and densitometry.

Development of experimental cataract can be objectively monitored in rats by application of Scheimpflug photography with the SL 45 Topcon camera and subsequent densitometric image analysis. The method has been used to study naphthalene cataract in Brown-Norway rats (BN-CPB), as well as diabetic cataract induced by streptozotocin injection in Sprague-Dawley rats. The values obtained by linear microdensitometric image analysis allowed precise characterization of the opacification with respect to size, topography, and time progress so that statistical evaluation of the efficacy of certain drugs in prevention or delay of experimental cataracts was possible.

Animals↗

Superoxide dismutase (SOD) in normal and cataractous human lenses.

Normal human lenses removed from eye bank eyes and cataractous lenses were assayed for superoxide dismutase (SOD) activity. In normal whole human lenses, SOD shows no marked difference in activity during aging. When comparing the activity in the nucleus with that in the equator, one finds that the activity in both lens parts has decreased with increasing age. The mean values of SOD are significantly lower in human lenses with mature cataract than in clear lenses. Interestingly, no residual activity could be proved in mature cataracts, whereas the activity in posterior subcapsular cataracts lay within normal limits.

Adult↗

[Biometry of the lens with respect to age and cataract morphology. Evaluation of Scheimpflug photos of the anterior segment].

Thickness of the lens, cortex and nucleus or nucleus with supranuclear layer, respectively, were determined for 58 controls aged 11-69 years (115 lenses), and for 175 patients aged 30-86 years with different types of cataract (247 lenses). Measurements of the densitograms of Scheimpflug photos (taken along the optical axis, magnified 10-fold) were performed, accurate to 0.5 mm (corresponding to 0.05 mm original size). The cataractous lenses were grouped in 5 morphological classes and 3 degrees of opacification (density according to the Scheimpflug photos). As regards normal lenses, the present authors' findings correspond to earlier findings of Niesel et al. (1976). Deviations from the normal pattern are found in typical cortical cataract (water-cleft and spokes cataract, wedge-shaped cataract) where nucleus and nucleus with supranuclear layer are thinner than the normal lenses, while with nuclear cataracts and mixed types the opposite is the case. In eyes with posterior cortical opacities no increase in the thickness of the anterior cortex is found with aging. With the true nuclear cataracts the increase in the thickness of the anterior cortex is negligible. The degree of opacification is closely related to an increase in the thickness of the nucleus and supranuclear layer, which implies a decrease in the thickness of the anterior cortex. Water-clefts and spokes of larger size cause the anterior cortex to become thinner. In eyes with wedge-shaped cataracts the different degrees of opacification did not affect the parameters measured.

Adolescent↗

Evaluation of the ocular safety of verapamil. Scheimpflug photography with densitometric image analysis of lens transparency in patients with hypertrophic cardiomyopathy subjected to long-term therapy with high doses of verapamil.

The ophthalmic examination of patients with hypertrophic cardiomyopathy treated with high doses of verapamil over a considerable period of time showed no evidence of a side effect of the drug, thus proving its ocular safety. This could be verified by densitometric image analysis of Scheimpflug photographs of the eyes. The data were used for statistical tests on lens transparency. Changes in lens transparency, i.e. a probable drug-induced cataract were found in none of the patients.

Cardiomyopathy, Hypertrophic↗

Investigations on lens transparency and its disturbances by microdensitometric analyses of Scheimpflug photographs.

During the aging process, the lens is subjected to changes of its pertinent properties which condition the transmission of light of different wavelengths. Between the second and the third decade, for instance, wavelengths below 400 nm are almost completely absorbed. The increase in lens thickness, effected by the appositional growth during life, might be considered responsible for this phenomenon, if the newly developing lens fibers in the outer periphery would synthesize proteins which, with respect to light transmission, differ from those formed during the embryonic phase. For such a phenomenon, however, no indication was found either by clinical observations or biochemical research. -Microdensitometric analysis of Scheimpflug-photographs of the anterior eye segment allows measurements of lens transparency in the single lens which directly depend on the respective wavelengths used in the photographic procedure. Investigations performed with this method on a normal age-grouped population, show that the changes in light transmission are most evident in two of the lens segments. The lens nucleus shows a continuous increase in light scatter during aging. Also the anterior cortex - particularly in the deeper layers - shows changes in light transmission. With advancing age (beginning between 30 and 40 years of age), increased lens fluorescence is found in the region of the deeper anterior cortex, which can be excited by UV wavelengths of 330-380 nm. This phenomenon is not found in the lens nucleus. The localization of the changes within the lens clearly shows that they are due to age-related modifications of the protein properties earlier designated as posttranslational or postsynthetic molecular modifications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Glutathione peroxidase, glutathione reductase and superoxide dismutase in the aging lens.

Glutathione reductase (GR) and glutathione peroxidase (GPx) show in bovine lenses a decrease in specific activity; furthermore, the heat lability of both enzymes increases with age monitoring structural changes of the molecules. GR activity was correlated with type of cataract in human lenses. Its decrease is significantly connected with cortical opacities. Superoxide dismutase activity declines in aging and cataractous lenses. These results support the assumption that in old lens tissue the capacity of the antioxidative scavanger system is diminished.

Adult↗

Lens metabolism and aging: enzyme activities and enzyme alterations in lenses of different species during the process of aging.

Extensive investigations on the metabolism of animal lenses over the life span indicate various changes that, regarded collectively, suggest a decrease in metabolic energy. A factor analytic interpretation and discussion of these results indicate that enzyme modifications might be one of the fundamental causes of the age-related changes in lens metabolism. Detailed investigations on the kinetic and physicochemical properties of certain enzymes of the carbohydrate breakdown in lenses of different ages verify this assumption. Since the changes observed are found mostly in the lens nucleus protein neosynthesis no longer takes place, posttranslational modifications appear to be responsible.

Aging↗