Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three newly detected dominant cataract mutations (Asc-1, Cat-3vao, Tcm) were investigated for effects on osmotic alterations in the lenses of heterozygotes. The lens wet weight was reduced in two mutant lines (Cat-3vao and Tcm), and the water content in the lenses of the Cat-3vao mice was increased. Moreover, in the cataractous lenses from Cat-3vao mice, the sodium-potassium-adenosine triphosphatase (Na(+)-K(+)-ATPase) activity was enhanced and the ATP concentration, correspondingly decreased. The osmotic variations observed in the Cat-3vao mutants might have been due to a metabolic response to the yet unknown, primary pathological event. The lenses of the other two mutant lines (Asc-1 and Tcm) revealed no alterations that could be related to osmotic stress. In no mutant line investigated could a decrease in Na(+)-K(+)-ATPase activity be demonstrated that was similar to the causative factor in the Nakano mutant line. The Cat-3vao mice exhibited some similarities to the Philly mutant line.
 ...
PMID:Osmotic state of lenses in three dominant murine cataract mutants. 216 48

Our earlier studies of cataracts in Dahl salt-sensitive (DS) rats suggested the possibility of altered lens ion transport as a contributing factor in cataractogenesis in this genetic model. We also observed that those weanling DS rats with the greatest pressor response to a high salt diet eventually developed cataracts, and that changes in salt intake modified cataract formation. In the present studies, we measured lens 86Rb uptake as an index of sodium-potassium adenosine triphosphatase [(Na+,K+)-ATPase] activity in weanling DS rats before the development of cataracts or sustained hypertension. Additionally, plasma renin activity was measured to indirectly assess our hypothesis that the difference between cataract-prone DS rats and DS rats unlikely to develop cataracts might be a difference in degree of salt sensitivity. At the age of 4 weeks, 50 DS and 25 salt-resistant (DR) rats were given a high sodium diet for 2 weeks, at which time the rats were divided into three groups based on the systolic blood pressure response, that is, cataract-prone DS rats with systolic blood pressure equal to or greater than 155 mm Hg, DS rats unlikely to develop cataracts with systolic blood pressure less than or equal to 125 mm Hg, and DR rats. Lens and aqueous humor Na+ and K+, lens dry weight, and water content were not significantly different among the three groups of weanling rats. Plasma renin activity was lowest in cataract-prone DS rats and low in DS rats unlikely to develop cataracts when compared with values in DR rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Lenticular rubidium uptake and plasma renin activity in weanling cataract-prone salt-sensitive rats. 240 57

Changes in the cation balance cause hydration and initiate the process of lens opacification. Such alterations were studied in human cataractous lenses and during the development of alloxan-induced diabetic cataract in rats by biochemical and histochemical techniques. The development of alloxan-induced cataract in rats was examined in vivo which showed cortical opacities beginning after 32 days. These opacities did progress to maturity after 64 days and finally the lenses were completely opacified after 96 days of alloxan treatment. The histochemical localization of sodium-potassium-activated adenosine triphosphatase using three different methods provided information on the possible role of this enzyme in normal and cataractous lenses. In human cataractous lenses, sodium-potassium adenosine triphosphatase activity was found to be considerably decreased, whereas no activity of this enzyme was localized in human diabetic cataractous lenses. An animal model provided evidence that an apparent decrease of sodium-potassium adenosine triphosphatase may be involved in the initiation of alloxan-induced diabetic cataract in rats.
 ...
PMID:Studies on cataractogenesis in humans and in rats with alloxan-induced diabetes. I. Cation transport and sodium-potassium-dependent ATPase. 298 22

Aldose reductase is a rate limiting enzyme in the polyol pathway associated with the conversion of glucose to sorbitol. The enzyme is located in the eye (cornea, retina, lens), kidney, myelin sheath, and also in other tissues less involved in diabetic complications. Experiments in diabetic animals have implicated sorbitol accumulation in the lens to the development of cataracts. The use of inhibitors of aldose reductase in animal studies has demonstrated that diabetic complications such as cataracts, nephropathy, and slowing of nerve conduction can be ameliorated. While an osmotic effect can explain the physical changes in the lens leading to cataract formation, the effect of sorbitol accumulation in other tissues and the resulting diabetic complications has been linked to the depletion of myoinositol content resulting in a derangement of sodium-potassium adenosine triphosphatase activity. Since glucose and other hexoses are poor substrates for aldose reductase, it is only in hyperglycemia when the enzyme hexokinase is saturated that aldose reductase is activated, leading to accumulation of sorbitol. The kinetics of inhibition of aldose reductase by a variety of inhibitors has been delineated. The dose required varies from inhibitor to inhibitor and is consistent with their inhibition constants. Toxicity is a consideration in the use of some of the inhibitors, as was demonstrated with sorbinil which caused hypersensitivity reactions in 10 percent of patients. Other inhibitors such as tolerant have shown efficacy and are under clinical investigation. Interpretation of results obtained with aldose reductase inhibitor therapy in human subjects suggest that these inhibitors are effective at early stages of diabetic complications.
 ...
PMID:Aldose reductase and its inhibition in the control of diabetic complications. 845 42

Sodium-potassium-adenosine triphosphatase (Na,K-ATPase) has long been recognized for its role in regulating electrolyte concentrations in the lens, within which the electrolyte balance is vital to lens transparency. In this study, we compared the abundance of the alpha-subunit of Na,K-ATPase in lens epithelia of patients with senile cataracts, in order to examine the role of this enzyme in various types of lens opacity. Human lens epithelia were collected from 27 patients with senile cataracts who had undergone phacoemulsification. The type and the severity of lens opacity were graded and scored according to the Lens Opacities Classification System II. The mean age of the patients was 67.5 years (range, 46-80 yr). Abundance of the Na,K-ATPase alpha-subunit peptide in the lens epithelium was quantified by means of Western immunoblotting. Immunoblotting revealed that the amount of Na,K-ATPase alpha-subunit tended to decrease with increased cataract severity. In hypermature cataracts, the Na,K-ATPase alpha-subunit was barely detectable. The amount of alpha-subunit of Na,K-ATPase was inversely correlated with the overall severity of cataract (r = -0.64, p = 0.002). However, the inverse correlation was significant only in the cortical region (p = 0.027). As the cortex is located adjacent to the lens epithelium, it is directly affected by the loss of function of Na,K-ATPase in the epithelium. Such loss could result in water accumulation, vesicles, water clefts, Morgagnian globule formation, and Morgagnian cataract.
 ...
PMID:Na,K-ATPase in lens epithelia from patients with senile cataracts. 1056 Feb 39

The focus of the study was to characterize plasma membrane calcium-ATPase pump (PMCA) isoform expression in the human lens and cultured lens epithelial cells as a basis for future studies of calcium homeostasis in the lens. Proteins and mRNA expression were analysed using Western Immunoblotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. Clear human lenses from the Kentucky Lions Eye Bank and an immortalized human lens epithelial cell line (HLE B-3) were used. RT-PCR products of PMCA1, PMCA2, and PMCA4 primers were detected at 429, 557, and 849bp, respectively. All these products were identified as PMCA isoforms by sequence analysis. Protein bands at approximately 130, 115, and 135kDa were detected by Western blot analysis for PMCA1, PMCA2 and PMCA4, respectively. PMCA3 was not detected at protein or mRNA level in any human lens sample or cell culture, but was detected in the rat brain cortex used as a control. Several bands with lower molecular weights, especially for PMCA2, were detected in the epithelial samples and probably represent break down products of PMCA2. No PMCA proteins or breakdown products were detected in the nuclear or cortical fractions from human lenses. PMCA1, 2, and 4 proteins and mRNAs are expressed in human lens epithelium and cultured epithelial cells; PMCA3 is not. PMCA was not detected at all in the lens fibre cells. The calcium pump must be selectively processed, independent of other membrane proteins such as the Na-K-ATPase pumps, because the distribution of the Na-K-ATPase pump is asymmetrical in the epithelium and present throughout the lens whereas the calcium pumps are not. The findings of this study provide a basis for further studies to examine the role and modulation of PMCA isoforms in calcium homeostasis and in the development of cataract.
 ...
PMID:Plasma membrane Ca2+-ATPase expression in the human lens. 1597 55

Epidemiological and experimental studies have revealed that lens epithelial cells exposed to ultraviolet B (UVB) light could be induced apoptosis, and lens epithelial cell apoptosis can initiate cataractogenesis. Posterior capsular opacification (PCO), the most frequent complication after cataract surgery, is induced by the proliferation, differentiation, migration of lens epithelial cells. Thus, inhibiting the proliferation of lens epithelial cells could reduce the occurrence of PCO. It is reported that zinc oxide (ZnO) nanoparticles have great potential for the application of biomedical field including cancer treatment. In the present study, we investigated the cytotoxic effect of ZnO nanoparticles on human lens epithelial cell (HLEC) viability. In addition, changes in cell nuclei, apoptosis, reactive oxygen species and intracellular calcium ion levels were also investigated after cells treated with ZnO nanoparticles in the presence and absence of UVB irradiation. Meanwhile, the expression of plasma membrane calcium ATPase 1 (PMCA1) was also determined at gene and protein levels. The results indicate that ZnO nanoparticles and UVB irradiation have synergistic inhibitory effect on HLEC proliferation in a concentration-dependent manner. ZnO nanoparticles can increase the intracellular calcium ion level, disrupt the intracellular calcium homeostasis, and decrease the expression level of PMCA1. UVB irradiation can strengthen the effect of reduced expression of PMCA1, suggesting that both UVB irradiation and ZnO nanoparticles could exert inhibitory effect on HLECs via calcium-mediated signaling pathway. ZnO nanoparticles have great potential for the treatment of PCO under UVB irradiation.
...
PMID:Zinc oxide nanoparticles inhibit Ca2+-ATPase expression in human lens epithelial cells under UVB irradiation. 2406 May 44

Currently, titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various applications including cosmetics, food additives and biomedicine. However, there are few reports available using TiO2 NPs to treat ocular diseases. Posterior capsular opacification (PCO) is the most frequent complication after cataract surgery, which is induced by the proliferation and migration of lens epithelial cells. Thus, inhibiting the proliferation of lens epithelial cells will efficiently reduce the occurrence of PCO. In this study, we investigated the effects of TiO2 NPs on HLE B-3 cells with or without ultraviolet B (UVB) irradiation in vitro. We found that TiO2 NPs can inhibit HLE B-3 cell growth, cause the elevation of intracellular [Ca(2+)], produce excessive reactive oxygen species (ROS), further reduce Ca(2+)-ATPase activity and decrease the expression of plasma membrane calcium ATPase 1 (PMCA1), finally disrupt the intracellular calcium homeostasis and induce cell damage. Importantly, UVB irradiation can apparently enhance these effects on HLE B-3 cells in the presence of TiO2 NPs. Taken together, the generation of excessive ROS and the disruption of intracellular calcium homeostasis may be both involved in TiO2 nanoparticle-induced HLE B-3 cell damage under UVB irradiation.
 ...
PMID:UVB irradiation enhances TiO2 nanoparticle-induced disruption of calcium homeostasis in human lens epithelial cells. 2505 45