The fluorescence of crystalline lens homogenates from CatFr-strain mice with hereditary cataract

The homogenate fluorescence of hereditary cataract in mice was studied. The changes of protein parameters and more extended long-wave fluorescence with mice having cataract were found. The possible reasons for decrease of intensity of protein and increase of nontryptophan fluorescence are being discussed.     

Studies on lens proteins of mice with hereditary cataract. I. Comparative studies on the chemical and immunochemical properties of the soluble proteins of cataractous and normal mouse lenses

Total soluble and insoluble proteins of the lens were similar in normal and hereditary cataractous mice up to 1 week of age. Thereafter, the normal mouse lens showed a continued increase in weight and protein content until 500 days of age. In cataractous mice, while the total protein content increased up to 60 days and reached a plateau, the soluble protein content declined dramatically from day 22 to day 60, and then the rate of decrease remained constant up to 500 days.At different ages, the soluble proteins were separated by gel filtration into the high molecular weight proteins, α-, β- and γ-crystallin fractions. All of these showed an age-related increase in the normal lens, and the relative values of α- and β-crystallins increased for a 410-day period. On the other hand, in the cataractous process, the high molecular weight protein increased, and α-, β- and γ-crystallins decreased: the degree was especially marked in γ-crystallin.Immunochemical studies indicated that the aggregation of β-crystaUin occurred much earlier in the cataractous lens than in the normal. Analysis of the amino acid composition and ultraviolet absorption spectre revealed no significant chemical differences between the crystallins of the normal and the cataractous lens.     

Study of soluble proteins of mouse crystalline lenses (normal and in cataract)

The water-soluble proteins from mice lenses (normal and cataract lenses) were investigated by methods of absorption spectrophotometry and kinetics of UV-induced radical decay. General characteristic of internal structure of extraction proteins was investigated by recombination kinetic method. It was shown that concentration of water-soluble proteins lowered ten times in lenses of mature cataract, i. e. 90% protein molecules were connected in lenses of mature cataract.     

Characterization of dominant hereditary cataract in DDD/1 mice

We found a female cataractous DDD/1-nu/+ mouse and established a hairy mutant strain (DDD/1-Cti/Cti) with 100% incidence of cataract from it by repeating sibmating. Genetic studies demonstrated that a single autosomal semidominant gene controls cataractogenesis. This gene was named Cti. In homozygotes, DDD/1-Cti/Cti, the lenses began to opacify at 14 days of fetal life and were recognized clinically as cataract at 13-14 days of age when the eyes first open. The opacification became more and more intense with age and looked like mature cataract at 28-42 days of age. However, clarification of the opacified lenses commenced at the periphery after 56 days of age and expanded to the inside with time, and only an opaque spot was left at the center at 140 days of age. In heterozygotes, DDD/1-Cti/+, the lenses were recognizable as cataract after 28 days and became like mature cataract around 35 days of age. The opacity began to be lightened at 42 days and the lenses appeared normal at 56 days of age. Both lenses and eyeballs developed in similar courses in DDD/1(-)+/+, -Cti/+ and -Cti/Cti, although slightly retarded in the last. Microphthalmia was not accompanied even in DDD/1-Cti/Cti. The lens water content remained higher during the time when intense lens opacity continued in DDD/1-Cti/Cti and -Cti/+. Background genes appeared to affect the expression of Cti. DDD/1-Cti(-)+ mice may provide a model for researches into clarification of opaque lenses. A discussion concerning the possible allelism of Cti and Cts with Lop was made based on their phenotypic characteristics.     

The fluorescence of mouse crystalline lenses at different stages of radiation cataract studied by synchronous scanning

Fluorescence of intact lenses of F1 (CBA x C57BL6) mice at different stages of X-ray cataract induced by gamma irradiation (5.00 Gr) has been studied by synchronous scanning of fluorescence, the shift between emission and excitation wave lengths being 20 nm. The ratio between peek intensities of the nontryptophan and tryptophan fluorescence within the synchronous scanning spectra (K) has increased 3.5 times as much at the stage of singular dot-like opacities. K-parameter correlated with GSH level in the lenses (r = -0.9). According to the results achieved, K could be regarded as an informative indicator of the development of X-ray cataract at the stage previous to turbidity.     

Change in potassium ion homeostasis of the crystalline lens in mice with hereditary cataracts (the CatFr line)

Fraeser mouse lens morphology and potassium homeostasis were studied. It was shown that just at the age of one month mouse lens exposed "bull" cells which could be observed in patients with senile cataract as well. Nucleated fusiform extended cells were found 4 months later in the central part of the lens which was not typical for this part of the whole normal lens. Studied homogenates of 34 mice with hereditary cataract demonstrated statistically significant increase (1.5-fold about) in K+-content estimated for the whole lens weight as compared to the control group (38 lens). The difference in potassium content in aqueous humor between affected and control animals was statistically indistinguishable. The role of potassium ions in Fraeser cataract pathogenesis is discussed.     

A defect of the myo-inositol maintenance mechanism in the lens of hereditary cataract mice

The myo-inositol uptake system was studied in lenses of normal and hereditary cataract mouse. The normal mouse was able to accumulate myo-inositol continuously from medium and keep it in a high concentration. The specific myo-inositol uptake was dependent on temperature and it decreased in Ca²⁺-free medium. In contrast, specific uptake of myo-inositol reached a plateau after 15 min in the cataract mouse lens although initial incorporation was more rapid than that in normal mouse lens. This uptake system was not affected by temperature or Ca²⁺ in the medium. The rate of myo-inositol efflux into the medium was more rapid in the cataract lens than that of the normal lens. It was shown that the low level of myo-inositol in the lens of hereditary cataract mouse was due to the defect of myo-inositol transport system and the enhanced efflux rate. These results suggest a dysfunction of the lens membrane.     

A study of a hereditary cataract in the mouse

This report presents a study of cataracts seen in a random-bred strain of Swiss mice with Balb/c mice used as a control group. The embryonic development, and histological and slit lamp observations of the lenses in the two groups of animals are contrasted. The cataract is dominant in its inheritance (Tissot, '62). It appears either unilaterally or bilaterally as a dense white opacity in the lens substance. The earliest sign of abnormal formation occurs at 14 days of embryonic development. This is associated with a defect in the primary lens fibers formation. Progressive degeneration of these fibers occurs until they are reduced to a mass of cellular debris seen at the last day of gestation. The secondary fibers are also laid down in an abnormal manner. The normal lamellar arrangement of the secondary fibers is not seen in cataractous lenses. The abnormal lens fiber development leads to progressive vacuolization. The mature cataract seen in the adult is filled with many vacuoles, the largest ones occurring at the equatorial region. The nuclear region consists of a clumpy eosinophilic mass with scattered calcified areas. The rate of growth of the secondary fibers is different from that of the normal group. Most of the mature cataracts in the adult contain a vascularized epithelium. There are three possible areas of primary involvement which may lead to the development of the cataract. This are: (1) A defect in the development of the primary lens fibers; (2) A defect in the development of the secondary lens fibers; (3) An abnormal lens epithelium which may interfere with nutrition of the lens and thus initiate cataract formation.     

Involvement of interleukin 18 in cataract development in hereditary cataract UPL rats

Our previous studies have demonstrated that lens epithelial damage by excessive nitric oxide causes an elevation in lens opacification in UPL rats, and it has been reported that interferon-gamma production in lens epithelial cells is involved in cataract development. In this study, we investigated the involvement of interleukin (IL)-18, which leads to interferon-gamma, in UPL rat lenses. The opacification of UPL rat lenses starts at 39 days of age. The gene expression levels causing IL-18 activation (IL-18, IL-18 receptor and caspase-1) are increased at 32 days of age, and the expression of mature IL-18 protein in the UPL rat lenses also increases with ageing. On the other hand, the interferon-gamma levels in UPL rat lenses are increased, and the increase in interferon-gamma levels in UPL rat lenses reaches a maximum at 39 days of age. Mature IL-18 expression and interferon-gamma production are achieved prior to the onset of lens opacification. In conclusion, the expression levels of IL-18 in the lenses of UPL rats are increased with aging. In addition, interferon-gamma levels in the lenses of UPL rats are also increased. It is possible that interferon-gamma generated by the activated IL-18 may induce cataract development in UPL rats.