Dietary sugar and salt represent real risk factors for cataract development.

Dietary sugar and salt represent etiological risk factors of human cataract. To verify etiological data on the basis of histological findings, 9 pigs with a body weight of 40 kg, 3 months of age, in groups of 3 were continuously fed with 5% of refined dietary sugar (sucrose - C(12)H(22)O(11)), 0.5% of salt (NaCl) and a sugar-salt mixture (2.5 + 0.25% accordingly) in their crude (unboiled) meal food during 3 months, which resulted in minor cataractous changes in the lens. In the second experiment, 10 weight- and age-matched animals were fed a chronic sugar and intermittent salt diet during 6 months; the other 10 animals served as controls. During the second experiment, crystallin leakage into the aqueous humor of the lens was detected, and a marked swelling of the lens fibers and fiber tips was noticed, indicating that excessive amounts of dietary sugar and salt are risk factors for the development of cataract in normal (nondiabetic) animals.

A novel mutation in the M1S1 gene responsible for gelatinous droplike corneal dystrophy.

PURPOSE: To identify the genetic defect in the M1S1 gene causing gelatinous droplike corneal dystrophy (GDLD) in an Estonian family. METHODS: DNA was extracted from members of a GDLD-affected family and control persons. Polymerase chain reaction followed by direct sequencing was used to detect mutations in the M1S1 gene. Sequencing results were confirmed with restriction analysis. RESULTS: Sequencing of the M1S1 gene revealed a novel mutation and a common polymorphism. All patients with GDLD were found to be homozygous for the insertion of nucleotide C in position 520 in M1S1. The mutation leads to formation of truncated protein. The mutation was excluded in 103 normal, unaffected individuals. Very close to the location where the mutation was identified in the M1S1 gene, a single-nucleotide polymorphism (518A/C) was found, changing aspartic acid to alanine at codon 173. CONCLUSIONS: The data indicate that mutation ins520C in the M1S1 gene is the primary cause of GDLD in the family studied.

Polymorphic glutathione S-transferase M1 is a risk factor of primary open-angle glaucoma among Estonians.

Primary open-angle glaucoma, the most common form of glaucoma is a slowly progressive atrophy of the optic nerve, characterized by loss of peripheral visual function and is usually associated with elevated intraocular pressure. The etiology and genetic risk factors of primary open-angle glaucoma are mostly unknown. The aim of this study was to find out whether the polymorphism at GSTM1, GSTM3, GSTT1 and GSTP1 loci is associated with increased susceptibility to glaucoma, because these polymorphic enzymes are susceptibility candidates for several diseases, including such eye disease as cataract. The phenotype of GSTM1 and GSTT1 was determined by ELISA and the genotype of GSTM3 and GSTP1 was detected by polymerase chain reaction. Four hundred and fifty two Estonians (250 glaucomas and 202 controls) participated in a case-control study. A significant association of the GSTM1 polymorphism with glaucoma was observed. The frequency of the GSTM1 positive individuals among the glaucoma group was significantly higher than in controls (60 vs. 45.0%) with odds ratio of 1.83 (95% CI 1.26-2.66;P = 0.002). The risk among the GSTM1 positive individuals of developing glaucoma was even higher in the case of smoking: 62.7% of smokers were GSTM1 positive in the glaucoma group while only 33.3% of smokers had GSTM1 positive phenotype in controls (OR = 3.36; 95% CI 1.49-7.56;P = 0.012). An association with a lower level of significance was also found with the GSTM3 gene. Four% of the 250 patients with POAG were identified as carriers of the GSTM3 BB genotype, a proportion which was slightly higher than the 1.0% for the controls (OR = 4.17; 95% CI 0. 90-19.24;P = 0.144). The frequencies of the GSTT1 and GSTP1 genotypes in both groups were not statistically different. The present study suggests that the GSTM1 polymorphism may be associated with increased risk of development of primary open-angle glaucoma.

Polymorphic glutathione S-transferases as genetic risk factors for senile cortical cataract in Estonians.

PURPOSE: To investigate the possible association between glutathione S-transferase GSTM1, GSTM3, GSTT1, and GSTP1 polymorphism and the occurrence of age-related cataracts in Estonian patients. METHODS: Patients with cortical (155), nuclear (77), posterior subcapsular (120), mixed type (151) of senile cataract and control individuals (202) were phenotyped for GSTM1 and GSTT1 by enzyme-linked immunosorbent assay and genotyped for GSTM3 and GSTP1 by polymerase chain reaction. RESULTS: The frequency of the GSTM1-positive phenotype was significantly higher in the cortical cataract group (60.6%) than in the controls (45.0%) with odds ratio of 1.88 (95% CI, 1.23-2.94; P = 0.004). The cortical cataract risk associated with the GSTM1-positive phenotype was increased in carriers of the combined GSTM1-positive/GSTT1-positive phenotype (OR = 1.99; 95% CI, 1.30-3.11; P = 0.002) and the GSTM1-positive/GSTM3 AA genotype (OR = 2.28; 95% CI, 1.51-3.73; P < 0.001). The highest risk of cortical cataract was observed in patients having all three susceptible genotypes (OR = 2.56; 95% CI, 1.59-4.11; P < 0.001). Also, a significant interaction between the presence of the GSTP1* A allele and cortical cataract was found with prevalence of the GSTP1* A allele among the cortical cataract cases compared with the controls. Ninety-five percent of subjects with cortical cataract had the GSTP1 (AA, AB, or AC) genotype, whereas in controls 87% of persons had a genotype with GSTP1*A allele (OR = 3.1; 95% CI, 1.31-7.35; P = 0.007). In contrast to the GSTP1*A allele, the presence of the GSTP1*B allele in one or two copies leads to decreased cortical cataract risk (OR = 0.09 for GSTP1 BB genotype). CONCLUSIONS. The GSTM1-positive phenotype as well as the presence of the GSTP1*A allele may be a genetic risk factor for development of cortical cataract.

Eye lens tumors: an experimental-histological and theoretical approach.

The eye lens is the only tissue in the organism where to date no spontaneous tumors have been described. In pathologic (cataractous) lenses, however, several abnormal cell growths have been described. General tissue properties of these cell growths (morphology, proliferation, formation of cell masses, etc.) are in accordance with characteristics of benign tumors in other tissues, and can therefore be considered as benign lens tumors.

No immunoglobulins in cataractous lenses.

All 47 human senile cataractous lenses studied by a direct immunohistochemical method for the presence of immunoglobulins yielded negative results. Consequently, cataract cannot be an autoimmune disease as has been suggested by some authors.

Ovarian carcinomas express a sperm acrosomal antigen, defined by monoclonal antibody 9H8.

A new monoclonal antibody (MAb 9H8, IgM class) reactive with human ovarian carcinoma has been raised after immunizing C57BL/6 mice with bovine sperm. Immunohistological studies indicated that 20/21 serous ovarian adenocarcinomas expressed 9H8-defined antigen but it was absent in benign ovarian tumors (0/11). 1/11 of breast carcinomas and 5/5 of rectal carcinomas expressed this antigen, although to a considerably lesser degree. Tumors of lung, skin, brain and mesothelium were negative. The antigen was also expressed in embryonic skin, in renal collecting tubule cells and in saliva. In bovine, human and mouse sperm the antigen is confined to the acrosomal region. The molecular weight of this antigen was determined by Western blot analysis and gel filtration. In SDS-PAGE the antigen ran as a broad band barely entering the 7% gel, indicating an apparent molecular weight > 300 kDa. In the absence of detergents and reducing agents this glycoprotein forms larger complexes (> 1,500 kDa) as determined by gel filtration on Sephacryl S300. The epitope contains carbohydrate structures recognized by lectin PNA (peanut agglutinin).

Histological differentiation in fetal organ-cultured and human cataractous eye lenses.

Swine fetal organ-cultured lenses were studied histoautoradiographically and histologically, and human cataractous lenses were examined histologically to investigate the continuous differentiation of epithelial cells into fiber cells in the lens equatorial region. Both lens groups studied presented abnormal differentiation: the equatorial epithelium proliferates; nucleus-containing cortical fibers turn into bladder cells (of Wedl), and the formation of new cortical fibers stops.

Proliferation of abnormal cells in fetal organ-cultured and human cataractous eye lenses.

Abnormal epithelioid, fibroblast-like, infiltrating, and bladder cell complexes of fetal swine organ-cultured lenses contained DNA-synthesizing cells, of which epithelioid and fibroblast-like cells proliferated. The same is supposed to be true for abnormal cells of human cataractous lenses.