Cause Of Cataract Research Articles

The relationship between cataract, cell swelling and volume regulation.

The cause of cataracts is not known. Data from epidemiological and case-control studies have suggested various risk factors, among them; sunlight, diabetes, diarrhoea, oxidative stress, smoking and alcohol. Many reports in the literature suggest that the hydrated state of the lens is linked to cataract and recently direct evidence has emerged linking lens swelling to cataract. This review attempts to collate the various strands of evidence relating the hydrated state of the lens in cataract and to construct a common pathway for cataractogenesis. This common pathway involves lens swelling, membrane permeabilization, vacuole and cleft formation, disturbance to the intracellular environment, protein aggregation/modification and light scatter. This hypothesis gives rise to some testable predictions amongst which is that under certain conditions the lens axial diameter will increase raising the possibility that pre-cataractous changes could be detected (e.g., by ultrasound) and, with appropriate action, the cataract could be prevented or delayed. There are encouraging signs from animal studies that certain types of lens opacification can be delayed or prevented, lending credibility to the objective of cataract prevention in humans. Even a delay in the onset of cataract would have a huge global impact. The incidence of cataract correlates with poverty, poor diet and poor hygiene and the vast majority of cataract is found in developing countries. Economic factors and a lack of cataract surgeons in these countries mean that surgery is not the long-term answer. Prevention is the only realistic global approach. This review concludes that detection of pre-cataractous changes and cataract prevention are achievable objectives and funds should be directed towards their realization.

INVITED EDITORIAL The Genetics of Cataract: Our Vision Becomes Clearer

I would like to thank Drs. Joe Horwitz, Muriel Kaiser-Kupfer, Mark Kantorow, Eric Wawrousek, and Sam Zigler for a close reading of the manuscript.

The relationship between cataract and climatic droplet keratopathy in Mongolia

This study evaluated the association between cataract, the commonest single blinding disorder worldwide, and climatic droplet keratopathy which was taken as an indicator of high exposure to ultraviolet sunlight. A sample of 4344 persons from rural Mongolia (1991-92) provided 8634 eyes for analysis of the relationship between cataract and climatic droplet keratopathy. Right and left eyes were combined (paired into matched sets), and analysed using a random-effects regression model. The results indicated an inverse association between cataract and climatic droplet keratopathy in person aged 55 years or older, whereby eyes with more advanced climatic droplet keratopathy had lower prevalence of cataract (age-adjusted odds ratio 0.53, p = 0.047). In the younger group of persons aged 40-54 years, the reverse was found, whereby cataract prevalence was higher in eyes that have climatic droplet keratopathy (age-adjusted odds ratio 13.19, p = 0.046). However, only a small proportion (4%) of all the cataracts occurred in this younger age stratum where the prevalence of cataract was 0.5%, compared to prevalence of 17% in eyes of persons aged 55 years or older. These findings cast further doubts upon the current thesis that lifetime exposure to high levels of ultraviolet sunlight is a major cause of cataract in developing countries.

The effect of cigarette smoke on the bovine lens

Smoking has recently been identified from epidemiological studies as a possible cause of cataract but the mechanism involved is not known. Therefore, our laboratory has initiated studies aimed at elucidating these mechanisms.Whole bovine lenses were cultured to examine possible effects of cigarette smoke on amino acid uptake and protein synthesis. Cigarette smoke, filtered to remove nicotine and tar which would not reach the eye in vivo, was bubbled through culture medium. Bovine lenses were incubated in this medium in the presence of [14C]‐leucine for four days. A significant decrease in uptake of [14C]‐leucine and a decrease in protein synthesis were found with smoke treated lenses. This is the first demonstration of an effect of cigarette smoke on the lens. Further work is needed to determine how this metabolic upset is mediated and how it could lead to cataract.

Sequence analysis of lens beta-crystallins suggests involvement of calpain in cataract formation.

Abnormal activation of the protease calpain in the lens may be a cause of cataracts. Cataracts were induced in 10-day-old rats by a single overdose of sodium selenite. The water-insoluble protein from the opaque lens nucleus was separated by two-dimensional electrophoresis, electroblotted onto membranes, and the NH2-terminal sequence of partially degraded beta-crystallin polypeptides determined. Selenite cataractous lenses contained four major structural proteins, beta B1, beta B3, beta A3/A1, and beta A4 crystallins, missing from 5 to 49 amino acids from their NH2 termini. Incubation of intact beta-crystallins with calpain II in vitro produced identical cleavage sites. This provided further evidence for the role of calpain in the production of light scattering insoluble protein in cataractous lenses and also suggested that a similar process may lead to lens protein insolubilization during aging.

Prevalence of Age-related Lens Opacities in a Population: The Beaver Dam Eye Study

Age-related lens opacities are common and are a frequent cause of loss of vision. The Beaver Dam Eye Study was designed to estimate the prevalence and severity of lens opacities in a rural community in the United States. Adults between the ages of 43 and 84 years, identified by private census, were examined and participated in the study (n = 4926). Photographs were taken of the lenses and were graded in masked fashion according to a standardized protocol. For nuclear sclerosis, more severe levels occurred more commonly in older age groups and in women. Overall, 17.3% had nuclear sclerosis more severe than level 3 in a 5-step scale of severity. Cortical opacities increased with increasing age and were more common in women. They were found in 16.3% of the population. Posterior subcapsular opacities occur in 6.0% of the population. There was a significant trend of greater prevalence at older ages, but no sex effect. The frequency of early cataract increased in both sexes through the age group 65 to 74 years, but declined in those 75 years of age and older. The frequency of late cataract increased consistently with age. Women were more severely affected than men. This study confirms that lens opacities are common in adults in the United States. These data are important for providing for social and health care needs. It is important to determine causes of cataracts in order to develop preventive programs.

6. Disease causation The role of epidemiological evidence

How can epidemiology contribute to understanding the cause of clinical disease? We discuss the nature of causality and the intrinsic limitations of all empirical science, including epidemiology, in establishing "proof" of causality. Our examples relate to eye disease: How the cause of blindness from retrolental fibroplasia was unravelled. How the congenital rubella syndrome was discovered as a cause of congenital cataract. How allopurinol was cleared from suspicion as a cause of cataract.

Aging in the eye lens: Roles for proteolysis and nutrition in formation of cataract

Age-related eye lens opacification is one of the leading causes of blindess. Cataract afflicts a majority of persons over age 75, and costs associated with cataract treatment or extraction are the largest line-item in the Medicare budget. In the lesser-developed nations, the problem is more acute since cataract frequently occurs at younger ages, and there are insufficient numbers of ophthalmologists to perform lens extractions. In this paper, we examine causes of cataract and approaches to delay this debility.

Relationship of cataract to radiation sensitivity.

Considerable exposure to radiation always causes posterior subcapsular cataract (PSC). This investigation was conducted to ascertain whether cellular hypersensitivity to radiation may be identified as a possible cause of cataract in persons exposed to low levels of radiation. Patients were studied in whom PSC had followed probable exposure to low levels of radiation or in whom PSC had developed before the age of 60 without known exposure. The patients with cataract were compared with age and sex matched controls without cataract. Radiation sensitivity was estimated by measuring clonal growth of skin fibroblasts and peripheral blood lymphocytes after exposure to graded doses of radiation and by measuring postirradiation reconstruction of separated nuclear material from lymphocytes. The results show variations in the level of radiation sensitivity between the patients, without significant differences from the controls. It is concluded that radiation hypersensitivity, as tested by the methods used in this study, is not normally associated with the development of posterior subcapsular cataract.

Cataract in Senescence Accelerated Mouse (SAM) 2. Development of a new strain of mouse with late-appearing cataract

A new strain of mouse with late-appearing hereditary cataract was developed in the Senescence Accelerated Mouse ( SAM-R 3 ). At the beginning of the selection of the new strain (generation 4), 5% of mice which lived over 20 weeks had cataract, at least unilaterally. During selection and brother-sister inbreeding, the incidence increased and reached 68% of 78 mice whose lifespan exceeded 20 weeks, in the 12th generation. In recent populations, (generations 9–14), the cataract began to appear around 10 weeks of age and about 81% of 64 females and 49% of 47 males had cataract after 32 weeks of age. Inflammatory lesions of the cornea and eyelids began to occur later in life and the incidence was lower than that of cataract. This observation suggested to us that the cataract of this new strain was not congenital in origin but rather was age-related and did not occur consequently after the onset of inflammatory lesions around the lens tissue. Stereomicroscopic examination of the lens revealed that many of these cataracts occurred initially at the posterior area and that the mature cataract showed a characteristic protrusion at the posterior pole and nuclear dislocation. Histology of the mature cataract also revealed protrusion of the posterior pole and showed degeneration and liquefaction of lens cortex, nuclear dislocation and destruction of posterior lens capsule. The wet weight, water and protein contents showed that the lens of this strain developed normally and that the untoward events were the result but not the cause of cataract. The SAM-R 3 strain should prove to be a suitable murine model for investigation of age-related changes in the lens, and cataractogenesis.

Lipid peroxidation as a possible cause of cataract

The role of free-radical-induced lipid oxidation in the development of human lens opacity was studied. Physico-chemical parameters of the lens fiber membranes at different stages of cataract have been investigated. The deterioration of lens fiber plasma membranes structure preceding formation of large aggregates in lenticular matter, leading to lens opacity, was observed by electron microscopy. Initial stages of cataract were characterized by the accumulation of primary (diene conjugates, cetodienes) lipid peroxidation (LPO) products, while in the later stages there was a prevalence of end LPO fluorescent products. Reliable increase in oxiproducts of fatty acyl content of lenticular lipids was shown by direct gas chromatography technique obtaining fatty acid fluorine-substituted derivatives. The lens opacity degree is found to correlate with the level of the end LPO fluorescent product accumulation in its tissue, accompanied by SH group oxidation of crystallins due to decrease of reduced glutathione concentration in the lens. The injection of LPO products into the vitreous has been shown to induce cataract. It was concluded that peroxide damage of the lens fiber membranes may be the initiatory cause of cataract development.

Avoidable blindness.

The vast majority of the world's 42 million blind are needlessly impaired. Epidemiologic studies are providing important insights into the cause of cataracts and provision of surgical services; ecologic approaches to the control of trachomatous corneal scarring; treatment and prevention of onchocerciasis; and early diagnosis and treatment of xerophthalmia among others. Continued research and application of existing knowledge can have a dramatic impact on the sight and lives of millions of people.

Thyroxine-binding globulin deficiency in Beckwith syndrome

swelling because of the osmotic activity of intracellular galactitol. With a block in galactose metabolism due to defective galactokinase activity, there is little or no formation of galactose-l-phosphate, so that the formation of galactitol and its excretion in the urine is the main route of galactose metabolism. ~ In classic galactosemia resulting from galactose-l-phosphate uridyl transferase deficiency, in which mental retardation and other symptoms are regularly seen in untreated patients, there is the accumulation of galactose-1-phosphate in addition to galactitol. It has been reasonable to assume that the symptoms other than cataracts are a consequence of the formation of large amounts of galactose-1-phosphate. If the mental retardation in our patients is a manifestation of the galactokinase deficiency, then the accumulation of galactose itself or of galactitol must play an etiologic role. The complete elucidation of the clinical spectrum of galactokinase deficiency must await the observation of greater numbers of patients. Since all infants and young children with cataracts should be examined for galactokinase deficiency 1~ and, when found, treated with a galactose free diet, the number of undiagnosed older children, such as we report here, should be few. The possibility that untreated patients may be mentally retarded adds a compelling reason for maintenance of stringent dietary therapy. REFERENCES 1. Segal S: Galactosemia, in Stanbury JB, Wyngaarden JB, and Fredrickson DS, editors: The metabolic basis of inherited disease, ed 4, New York, 1978, McGraw-Hill Book Company, Inc., pp 160-181. 2. Gitzelmann R: Deficiency of erythrocyte galactokinase in a patient with galactose diabetes, Lancet 2:670, 1965. 3. Ng WG, Donnell GN, and Bergren WR: Galactokinase activity in human erythrocytes of individuals at different ages, J Lab Clin Med 66:115, 1965. 4. Ng WG, Bergren WR, and Donnell GW: An improved procedure for the assay of hemolysate galactose-l-phosphate uridyltransferase activity by the use of labeled galactose-l-phosphate, Clin Chim Acta 15:489, 1967. 5. Pickering WR, and Howell RR: Galactokinase deficiency: Clinical and biochemical findings in a new kindred, J PEDIATR 81:50, 1972. 6. Gitzelmann R: Hereditary galactokinase deficiency, a newly recognized cause of juvenile cataracts, Pediatr Res 1:14, 1967. 7. Litman N, Kanter A, and Finberg L: Galactokinase deficiency presenting as pseudotumor cerebri, J PEDIATR 86:410, 1975. 8. Cogan DD: The lens, cataracts and galactosemia, N Engl J Med 288:1240, 1973. 9. Quan-Ma R, and Wells W: The distribution ofgalactitol in tissues of rats fed galactose, Biochem Biophys Res Commun 20:486, 1965. 10. Beutler E, Matsumoto F, Kuhl W, Krill A, Levy N, Sparkes R, and Degnan M: Galactokinase deficiency as a cause of cataracts, N Engl J Med 288:1203, 1978.

Dermatological and Ocular Examinations in Rabbits Chronically Photosensitized with Methoxsalen

Four groups of female Dutch-belted rabbits (Oryctulagus cuniculus) were given methoxsalen (12 mg/kg) or placebo by oral intubation and 1 hr later were exposed to UVA for either 2 or 8 hr. This procedure was repeated 5 days each week for 18 mo. A fifth group received no drug and no UVA exposure. The skin of the animals given methoxsalen and UVA showed signs of acute and chronic phototoxicity. Multiple peripheral blood parameters of hepatic, renal and hematologic function were normal and were not different between groups. Complete ophthalmoscopic examinations were performed periodically. No cataracts were seen in any of the animals. This data provides the perspective that in one species the daily dose of methoxsalen and UVA required to induce chronic cutaneous photosensitization is lower than the daily dose required to induce cataracts. It is inadvisable to interpret this data as suggesting that no risk exists for patients being treated with oral methoxsalen photochemotherapy. The experimental evidence supporting photosensitization as a cause of cataracts and implicating a role of lens DNA in this cataractogenesis is reviewed. Because methoxsalen-UVA alterations of lens DNA or protein could lead to delayed onset of cataracts, and because of the serious nature and potential preventability of phototoxic lens opacification, appropriate protective eye wear is recommended for all patients receiving oral psoralen photochemotherapy.

The proportion of protein from the normal and cataractous human lens which exists as high molecular weight aggregates in vitro

In the normal human lens high molecular weight aggregates (≥ 20 × 10 6 daltons) have been found to comprise only 3·1% of the total soluble protein and this percentage does not increase with age. In cataract the proportion is higher, representing 8·5% of the total soluble proteins, and much of it (5·1%) appears to be held together by disulphide bonds. These values are lower than those reported in the literature and do not support the suggestion that aggregation of human lens protein could be a cause of cataract.

Ultrastructure of Human Traumatic Cataract

Although electron microscopy has been used to study human senile subcapsular and electric cataract, no previous electron microscopic study has described human traumatic cataract. Such a study is of interest not only on a purely pathologic basis, but also affords the op­ portunity to document the sequence of events in cataractogenesis, since the exact time of the initial event, i.e., the trauma, is known. In this report we compare three lenses: one (Case 1) was penetrated inferiorly two weeks before extraction; another (Case 2) was penetrated inf eriorly 11 months before extraction. Neither patient had any other predisposing cause for cataract, and the contralateral eye in each case had a clear lens and visual acuity of 20/20. A clear, presumably normal lens (Case 3) was obtained at surgical enuclea­ tion for a malignant melanoma and served as the control against which ultrastructural changes in the injured lenses were compared.

Cataract in Hatchery Lake Trout

Abstract In 1957, when control of the sea lamprey appeared imminent, production of lake trout (Salvelinus namaycush) in hatcheries was increased. Coincident with this increase, certain diseases of lake trout became evident. One disease, cataract, results in permanent damage to the eye Several experiments to investigate the cause of cataract were conducted over a period of 3 years; 3 with diets, 3 involving light intensity (Allison, 1962), 1 in handling, and 1 experiment with injections of excess riboflavin. The experiments with diet, handling, and riboflavin injections did not provide control of cataract.

Treatment of Cataract

CATARACT is an opacity of the lens of the eye, which causes reduction of vision in varying degrees. It is not a film or growth as is popularly supposed. For purposes of study we can divide cataract into the following types: 1. Senile: occurring in middle and later life. 2. Due to disease or toxic substances, e.g., diabetes, dinitrophenol poisoning, et cetera. 3. Traumatic: occurring as the result of an injury such as a blow to the eye. 4. Congenital: occurring in utero and present at birth. We are most concerned with the first type. Cataractous changes are often noted in the late fifties and increasingly so during the next two decades. They may be sufficient to cut down vision to the point where vision is uncomfortable or they may be so slight that the patient is unaware of any change. The first symptom is a lessening of vision. If the opacity is in the cortex of the lens, the patient will be most comfortable in bright light where the pupil is well contracted. If the opacity is in the nucleus, the patient will see best in dim light where the pupil dilates slightly, allowing better vision through the periphery of the lens. We do not know why senile cataract occurs. It appears to be a part of the general aging process in which tissues lose some of their elasticity and undergo the usual changes of age. The speed with which these changes come to the lens is quite unpredictable, and we have no way at present of arresting the process. Various theories have been offered as to the cause of cataract. Some think that diet plays a part, others feel that a change in the blood sugar level is a cause in all cases (even when diabetes is not present), still others look to a hormonal dysfunction. At present, we

NASAL SENSITIVITY TO VASOCONSTRICTORS

MEDICAL literature contains many examples of pathologic conditions arising from the use of drugs given for the relief of various diseases or symptoms. One of the earliest examples is that represented in the symptoms due to withdrawal of cocaine, a drug which was not at first known to be habit forming. Many doctors themselves became addicted to its use. Two striking examples in recent years of pathologic states arising from the action of drugs are cataract formation from the use of dinitrophenol and granulocytopenia from the use of aminopyrine. Aminopyrine had come into wide use several years prior to the reports of a strange new disease, termed agranulocytosis. A causal connection with the drug was not discovered until some years later. Dinitrophenol was used for reducing weight for some time before it was recognized to be a cause of cataracts. In medical literature there are many other instances of the

CATARACT AND DIABETES

The field of the relation of disturbances of carbohydrate metabolism to cataract was chosen as one fertile for research into the cause of cataract because of the well known frequency of changes in refraction and development of lens opacities in diabetic subjects. Berndt as early as 1834 reported diabetes as a cause of cataract. Duke-Elder differentiated two types of cataract occurring in diabetes: (1) the form of senile cataract appearing frequently and at a relatively early age and (2) a characteristic form peculiar to the disease occurring more rarely. Duke-Elder felt that the diabetic state, by subjecting the lens to an abnormal traffic of fluid, induced the condition and tended to alter its type. He thought that the denaturing action of radiant energy in the presence of excessive sugar and acetone was probably the main factor in the production of cataract in diabetic persons. One must also consider