Indian J Ophthalmol 1991 Oct-Dec;39(4):148-50

Clinico-biochemical study of experimental complicated cataracts.

Sihota R, Mohan M, Angra SK, Mathur RL

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of

Medical Sciences, New Delhi.

Clinically observed complicated cataracts, generally do not have a definite causal factor. We studied the effects of E. coli toxin injected suprachoroidally, to simulate the effect of toxins released by extraocular organisms on the lens. 79.2% of eyes had a definable cataract at the end of the 6th week of observation. The biochemical changes portrayed an increased oxidative activity in the lens, evidenced by a fall in glutathione concentration, and the consequent tertiary reorientation of proteins to increase insoluble proteins, forming a cataract.

PMID: 1810872, UI: 92241956

Br J Ophthalmol 1991 Aug;75(8):476-9

Comparison of the effects of intraocular irrigating solutions on the corneal endothelium in intraocular lens implantation.

Matsuda M, Kinoshita S, Ohashi Y, Shimomura Y, Ohguro N, Okamoto H, Omoto T, Hosotani H, Yoshida H

Department of Ophthalmology, Osaka University Medical School, Japan.

We conducted a randomised prospective controlled study to determine the effects of a glucose glutathione bicarbonate solution (BSS Plus) and a citrate acetate bicarbonate solution (S-MA2) on the corneal endothelium in patients undergoing extracapsular cataract extraction with posterior chamber lens implantation. One eye of each patient was randomly assigned to receive BSS Plus, and the other eye to receive S-MA2. BSS Plus caused significantly less corneal swelling on the first postoperative day than did S-MA2. There was no difference between the two solutions in their effect on corneal thickness one week and one month postoperatively. Computer assisted morphometric analysis of wide-field specular microscopic photographs demonstrated minimal changes in endothelial morphological characteristics in the eyes irrigated with BSS Plus. By comparison S-MA2, caused a significant loss of endothelial cells and a marked reduction in the figure coefficient. These results indicated that BSS Plus has a clinical advantage over S-MA2 with respect to the corneal endothelium.

Publication Types:

Clinical trial

Randomized controlled trial

PMID: 1873266, UI: 91337999

Proc Natl Acad Sci U S A 1991 Jun 1;88(11):4656-60

(Published erratum appears in Proc Natl Acad Sci U S A 1991 Aug 1;88(15):6898)

Glutathione deficiency decreases tissue ascorbate levels in newborn rats: ascorbate spares glutathione and protects.

Martensson J, Meister A

Department of Biochemistry, Cornell University Medical College, New York, NY

10021.

Glutathione deficiency in newborn rats, produced by administration of L-buthionine-(S,R)-sulfoximine, a transition-state inactivator of gamma-glutamylcysteine synthetase, decreases ascorbate levels of kidney, liver, brain, and lung. These tissues, especially their mitochondria, undergo severe damage and the animals die within a few days. When glutathione levels are markedly decreased, ascorbate levels decrease leading to formation of dehydroascorbate, which is degraded. Ascorbate has high antioxidant activity, but it (and other antioxidants such as alpha-tocopherol) must be maintained in reduced forms. These studies show in vivo that an important function of glutathione is to maintain tissue ascorbate. Administration of large doses of ascorbate (but not of dehydroascorbate) to buthionine sulfoximine-treated newborn rats decreases mortality, leads to normal levels of ascorbate, and spares glutathione. Newborn rats given lower doses of buthionine sulfoximine develop cataracts that, as shown previously, can be prevented by giving glutathione monoester; as found here, such cataracts can be partially prevented by administration of high doses of ascorbate or dehydroascorbate. Ascorbate spares glutathione indicating that these compounds have similar antioxidant actions. Ascorbate may have reductive functions that are not efficiently performed by glutathione. Although glutathione normally functions to maintain ascorbate, alpha-tocopherol, and other cellular components in reduced states, ascorbate can serve as an essential antioxidant in the presence of severe glutathione deficiency.

PMID: 2052548, UI: 91271252

Exp Eye Res 1991 May;52(5):563-8

Prevention of selenite cataract by vitamin C.

Devamanoharan PS, Henein M, Morris S, Ramachandran S, Richards RD, Varma SD

Department of Ophthalmology, University of Maryland School of Medicine,

Baltimore 21201.

Studies have been conducted to determine the efficacy of vitamin C in the prevention of cataracts induced by selenite. Administration of the latter to rat pups results in the development of advanced cataracts within 5 days. Treatment with ascorbate had a significant preventive effect. The observations indicate that selenite cataract is due to an oxidative stress to the lens. In addition, the findings are in conformity with our view that ascorbate functions as an anticataractogenic substance.

PMID: 2065724, UI: 91293228

Invest Ophthalmol Vis Sci 1991 May;32(6):1916-24

Rapid deterioration of lens fibers in GSH-depleted mouse pups.

Calvin HI, Medvedovsky C, David JC, Broglio TM, Hess JL, Fu SC, Worgul BV

Department of Ophthalmology, University of Medicine and Dentistry of New Jersey,

New Jersey Medical School, Newark 07103.

Lens opacities developed within 48-72 hr in mice that received a series of eight injections of L-buthionine sulfoximine, a specific inhibitor of glutathione (GSH) biosynthesis, on postnatal days 8 and 9. Initial histopathologic features consisted of swollen fibers in the central anterior cortex and displacement of cell nuclei from the bow region to the posterior cortex. These aberrations suggest early fiber cell membrane and/or cytoskeletal dysfunction. A massive wave of fiber cell lysis then engulfed the entire lens cortex and nucleus within 24 hr and left only epithelial cells intact, suggesting a concerted mechanism of cataract generation. The acellular core of the mature cataract seen on postnatal day 16 consisted of a granular matrix in which pycnotic and fragmented cell nuclei were located near the terminus of the lens epithelium. The epithelium displayed increased mitotic activity and meridional row disorganization. During the next two weeks, rapid regeneration of lens fibers, displacement of the acellular necrotic cytoplasm to the center and rear of the lens, and vacuole formation were observed. As new fibers were differentiated, partial regeneration of the bow was seen. However, the cataract was irreversible.

PMID: 2032811, UI: 91236374

Indian J Exp Biol 1991 May;29(5):452-5

Glutathione and glutathione-related enzymes in busulfan treated rat lens.

Cherian M, Rawal UM

Zoology Department, School of Science, Gujarat University, Ahmedabad, India.

Glutathione (GSH) and GSH-related enzymes, glutathione reductase (GR), gamma-glutamyl cysteine synthetase (gamma-GCS), gamma-glutamyl transpeptidase (gamma-GTP), glutathione S-transferase (GST) and adenosine triphosphatase (ATPase) enzymes were analysed to study the effect of busulfan on the defence mechanisms of the lens. All these enzymes were found to increase significantly except GSH which showed only 7.9% increase as compared to controls in precataractous stage. These results affirm that busulfan is capable of evoking a response from the enzymes involved in the various pathways of GSH enabling the lens to prolong its clarity. The cataractous lenses showed significant decrease in all these parameters. Here, the impairment of the defense mechanism (GST, GR) and the total ATPase may be attributed to the cumulative action of the drug which can react with -SH groups of these enzymes, ultimately causing

opacification.

PMID: 1916943, UI: 92010087

Ann Ophthalmol 1991 Mar;23(3):101-5

Intraocular irrigating solutions: a clinical study of BSS plus and dextrose bicarbonate lactated Ringer's solution.

Kramer KK, Thomassen T, Evaul J

Department of Clinical Investigation, Walter Reed Army Medical Center,

Washington, DC 20307-5001.

Intraocular irrigating solutions of varying compositions and costs are available for cataract surgery. We studied preoperative and two months postoperative extracapsular cataract extraction and intraocular lens implant corneal endothelial cell size in two groups. One group had received an intraoperative irrigating solution of lactated Ringer's with dextrose and bicarbonate. The other irrigating solution was BSS Plus which differs chiefly in the presence of glutathione. A nonstatistically significant trend in favor of BSS Plus was observed.

Publication Types:

Clinical trial

Randomized controlled trial

PMID: 2039173, UI: 91247744

Ophthalmic Res 1991;23(3):133-40

Glutathione and glutathione-related enzymes in human cataractous lenses.

Xie PY, Kanai A, Nakajima A, Kitahara S, Ohtsu A, Fujii K

Department of Ophthalmology, Juntendo University School of Medicine, Tokyo,

Japan.

Glutathione and its related enzymes were measured for normal and cataractous human lenses. Glutathione decreased progressively with the development of cataracts. This decrease was more pronounced in the nucleus than in the capsule-epithelia of cataractous lenses. Glutathione reductase in nuclear extracts was relatively unchanged during cataract progress, while glutathione synthetase was significantly low in the advanced stages of cataracts. gamma-Glutamylcysteine synthetase was not measurable in the nuclei of

cataractous lenses.

PMID: 1945285, UI: 92050652

Lens Eye Toxic Res 1991;8(2-3):353-71

Lens coenzymes and cataract formation.

Leus NF

Biochemical Laboratory Odessa Academician Filatov Research Institute of Eye

Diseases and Tissue Therapy, USSR.

The present work discusses the role of certain coenzymes in the metabolic and the biophysical processes maintaining the nativity of lens components. It also analyses results of the levels of oxidized and reduced forms of nicotine amide coenzymes and glutathione in the lens folling insults by both physical and chemical cataractogenic agents. The role of flavine and flavine coenzymes in the maintainance of the biochemical and biophysical stability of the lens has also been discussed. Data concerning the enzymatic biosynthesis and degradation of the lens coenzymes has been presented.

Publication Types:

Review

Review, tutorial

PMID: 1911645, UI: 92001864

Ophthalmic Res 1991;23(1):51-8

Anticataractogenic property of gamma-glutamylcysteine ethyl ester in an animal model of cataract.

Ohtsu A, Kitahara S, Fujii K

Teijin Institute for Biomedical Research, Tokyo, Japan.

The anticataractogenic potential of gamma-glutamylcysteine ethyl ester was investigated in model cataracts induced by L-buthionine sulfoximine. Subcutaneous injection of the ester (0.625-2.5 mmol/kg) effectively inhibited cataractogenesis in suckling mice. Treatment of mice with L-buthionine sulfoximine alone resulted in a marked reduction of the glutathione content in the eyes. This deprivation of glutathione was mitigated, to a significant degree, by coadministering gamma-glutamylcysteine ethyl ester. In an experiment with rat lens in culture, gamma-glutamylcysteine ethyl ester was found to elevate the lenticular level of glutathione. These results indicate that gamma-glutamylcysteine ethyl ester is able to permeate across biomembranes and serves as an excellent precursor for glutathione biosynthesis, thereby exerting its anticataractogenic activity.

PMID: 1870842, UI: 91333946

Ophthalmic Res 1991;23(5):272-83

Naphthalene-induced cataract in the rat. II. Contrasting effects of two aldose reductase inhibitors on glutathione and glutathione redox enzymes.

Tao RV, Holleschau AM, Rathbun WB

Department of Ophthalmology, University of Illinois, Chicago.

This investigation compared the effects of two types of aldose reductase inhibitors on several biochemical parameters in naphthalene-induced cataract of the rat over a time span of 102 days of treatment. Feeding of naphthalene daily to brown Norway rats resulted in gradual, progressive development of zonular opacities. As compared to control animals, the values of soluble protein, soluble glutathione (total of oxidized plus reduced) and activities of glutathione peroxidase and glutathione reductase were decreased in rats fed either naphthalene or naphthalene + FK366, a carboxylic-acid-type aldose reductase inhibitor. In marked contrast, treatment with A11576, a hydantoin-type aldose reductase inhibitor, maintained the values of most parameters (with one exception) at levels that were similar to those of the controls, and all lenses remained clear. A decline of glutathione was noted in all naphthalene-fed rats, irrespective of whether these animals had been treated with an aldose reductase inhibitor. The great decrease of glutathione with A11576 suggests that this inhibitor acts at some step in naphthalene metabolism following formation of naphthalene epoxide.

PMID: 1784459, UI: 92149994

Arch Toxicol 1991;65(7):606-7

Effects of inhaled ethylene oxide on the lens glutathione redox cycle in rats.

Fujishiro K, Mori K, Inoue N

Department of Environmental Toxicology, University of Occupational and

Environmental Health, Kitakyushu, Japan.

The effects of chronic ethylene oxide (EtO) inhalation on the lens glutathione redox cycle were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, glutathione reductase decreased significantly in the lens while glutathione peroxidase did not. Glutathione reductase activity decreased time dependently, by as much as 81% after 13 weeks. In spite of changes in the glutathione redox cycle, reduced and oxidized glutathione levels were not affected. Our results raise the possibility that EtO inhalation may produce a cataract via changes in the glutathione redox cycle.

PMID: 1781743, UI: 92143693

Free Radic Res Commun 1991;12-13 Pt 2:609-20

Free radical enhancer xenobiotic is an inducer of cataract in rabbit.

Bhuyan KC, Bhuyan DK, Podos SM

Mount Sinai School of Medicine, City University of New York, N.Y. 10029.

Free radical enhancers, diquat, paraquat, plumbagin and juglone were used to study the oxy radical-induced damage to the rabbit lens in vitro and in vivo. Each compound caused a 6-8 fold increase in malondialdehyde (MDA) and a 30-55% decrease in reduced glutathione of the lens in vitro. These peroxidative and oxidative changes were potentiated in the presence of 100% O2, abolished by N2 and prevented by desferal-Mn (III) (DF-Mn) or liposomal superoxide dismutase (LSOD) indicating the involvement of O2-. Diquat injected intravitreally as a single dose (300 nmole in 30 microliters of isotonic saline) in the right eye of a 5-wk-old Dutch belted rabbit, induced early cataract after 24-72 h. The lens of the contralateral control eye injected with isotonic saline had no change. In the right eye, O2-. and OH. productions were significantly (P less than 0.01) higher; O2-. was about 16 fold higher in the aqueous humor and vitreous humor, and 5 fold in the lens and retina, and OH. was 35 fold higher in the aqueous humor, 2 fold in vitreous humor and 5 fold in the lens and retina as compared to the respective tissues of the control eye. Enhanced lipid peroxidation in the lens was apparent from the higher levels of MDA and formation of aminophospholipid.MDA Schiff-base conjugates. We propose that cyclic oxidation-reduction of xenobiotics coupled to the endogenous redox systems in the eye, could generate oxy radicals in excessive amounts, triggering cataractogenesis.

PMID: 1648013, UI: 91285494

MPS 1991;14(2):31-6

Cataract risk factors: blood level of antioxidative vitamins, reduced glutathione and malondialdehyde in cataractous patients.

Libondi T, Costagliola C, Della Corte M, Facchiano F, Menzione M, Savastano S,

Simonelli F, Rinaldi E, Auricchio G

Eye Clinic First Medical School, Naples, Italy.

Since many years experimental evidences have suggested an association between nutrition and lens opacities. A dietary deficiency of antioxidants and reactive oxygen scavengers may be involved in the pathogenesis of the "idiopathic" human senile cataract, as it has been demonstrated in some experimental cataracts. We tested the levels of ascorbic acid (vit. C), alpha-tocopherol (vit. E), reduced glutathione (GSH) and malondialdehyde (MDA) in the plasma or in the red blood cells (RBC) of 42 patients who were affected by surgically significant cataract and of 40 age-matched controls. Plasma vit. C mean level was 4.46 gamma/ml in cataracts and 4.62 gamma/ml in controls, while vit. E level was 7.70 and 7.09 gamma/ml respectively. RBC GSH was found to be 342 gamma/ml in cataracts and 346 in controls, while the MDA content was 4.06 picoMol/ml and 4.08 picoMol/ml respectively. The level of each tested nutrient or metabolite was not found to be statistically different between cataractous patients and controls, nor any significant trend was found to be present when the nutrients and metabolites were correlated to each other. Our results do not support the hypothesis of a nutritional deficiency in human senile cataracts. However, a defect in the antioxidative metabolism pathways could be present either systemically or at lens level.

PMID: 1369641, UI: 95319340