A contributory role of oxidative stress and protection by antioxidant nutrients have been suspected in cataract formation. Ganoderic acid A (GAA), an effective lanostane triterpene, is widely reported as an antioxidant. The aim of this study is to investigate the potential effects of GAA on cataract formation. After lens epithelial cells (LECs) were exposed to UVB radiation for different periods, cell viability, apoptosis-related protein levels, malondialdehyde (MDA) and superoxide dismutase (SOD) activities were monitored. We found that cell viability, the Bcl-2/Bax ratio and SOD activity were increased, while Cleaved caspase-3 levels and MDA activity were decreased compared with those in UVB-impaired LECs after GAA treated. Furthermore, GAA activated PI3K/AKT in UVB-impaired LECs and effectively delayed the occurrence of lens opacity in vitro. In conclusion, these findings demonstrated that GAA exhibited protective functions in SRA01/04 cells and rat lenses against UVB-evoked impairment through elevating cell viability and antioxidant activity, inhibiting cell apoptosis, activating the PI3K/AKT pathway and delaying lens opacity.
Animals ; Apoptosis ; Cataract/prevention & control* ; Cell Line ; Cell Survival ; Epithelial Cells/radiation effects* ; Heptanoic Acids/pharmacology* ; Humans ; Lanosterol/pharmacology* ; Lens, Crystalline/radiation effects* ; Malondialdehyde/metabolism* ; Rats ; Superoxide Dismutase/metabolism* ; Ultraviolet Rays/adverse effects*

β/γ-Crystallins are predominant structural proteins in the cytoplasm of lens fiber cells and share a similar fold composing of four Greek-key motifs divided into two domains. Numerous cataract-causing mutations have been identified in various β/γ-crystallins, but the mechanisms underlying cataract caused by most mutations remains uncharacterized. The S228P mutation in βB1-crystallin has been linked to autosomal dominant congenital nuclear cataract. Here we found that the S228P mutant was prone to aggregate and degrade in both of the human and E. coli cells. The intracellular S228P aggregates could be redissolved by lanosterol. The S228P mutation modified the refolding pathway of βB1-crystallin by affecting the formation of the dimeric intermediate but not the monomeric intermediate. Compared with native βB1-crystallin, the refolded S228P protein had less packed structures, unquenched Trp fluorophores and increased hydrophobic exposure. The refolded S228P protein was prone to aggregate at the physiological temperature and decreased the protective effect of βB1-crystallin on βA3-crystallin. Molecular dynamic simulation studies indicated that the mutation decreased the subunit binding energy and modified the distribution of surface electrostatic potentials. More importantly, the mutation separated two interacting loops in the C-terminal domain, which shielded the hydrophobic core from solvent in native βB1-crystallin. These two interacting loops are highly conserved in both of the N- and C-terminal domains of all β/γ-crystallins. We propose that these two interacting loops play an important role in the folding and structural stability of β/γ-crystallin domains by protecting the hydrophobic core from solvent access.
Amino Acid Substitution ; Cataract ; genetics ; metabolism ; HeLa Cells ; Humans ; Molecular Dynamics Simulation ; Mutation, Missense ; Protein Aggregation, Pathological ; genetics ; metabolism ; Protein Domains ; Protein Structure, Secondary ; Proteolysis ; beta-Crystallin B Chain ; chemistry ; genetics ; metabolism

Xanthoma is a relatively rare soft tissue lesion on the Achilles tendon and is usually associated with hyperlipidemia (lipid metabolism abnormality), mental retardation, cataract and atherosclerotic disease. We report on a case of normolipidemic bilateral Achilles tendon xanthoma without any notable cause. We herein describe the case where we achieved a satisfactory result by subtotal resection.
Achilles Tendon* ; Cataract ; Humans ; Hyperlipidemias ; Intellectual Disability ; Metabolism ; Xanthomatosis*

OBJECTIVETo evaluate the aldose reductase inhibitory (ARI) activity of different fractions of Hybanthus enneaspermus for potential use in diabetic cataract.

METHODSTotal phenol and flavonoid content of different fractions was determined. ARI activity of different fractions in rat lens was investigated in vitro.

RESULTSThe results showed significant level of phenolic and flavonoid content in ethyl acetate fraction [total phenol (212.15±0.79 mg/g), total flavonoid (39.11±2.27 mg/g)] and aqueous fraction [total phenol (140.62±0.57 mg/g), total flavonoid (26.07±1.49 mg/g)] as compared with the chloroform fraction [total phenol (68.56±0.51 mg/g), total flavonoid (13.41±0.82 mg/g)] and petrolium ether fraction [total phenol (36.68±0.43 mg/g), total flavonoid (11.55±1.06 mg/g)]. There was a significant difference in the ARI activity of each fraction, and it was found to be the highest in ethyl acetate fraction [IC50 (49.26±1.76 µg/mL)] followed by aqueous extract [IC50 (70.83±2.82 µg/mL)] and it was least in the petroleum ether fraction [IC50 (118.89±0.71 µg/mL)]. Chloroform fraction showed moderate activity [IC50 (98.52±1.80 µg/mL)].

CONCLUSIONSDifferent fractions showed significanct amount of ARI activity, where in ethyl acetate fraction it was found to be maximum which may be due to its high phenolic and flavonoid content. The extract after further evaluation may be used in the treatment of diabetic cataract.

Aldehyde Reductase ; antagonists & inhibitors ; Animals ; Cataract ; drug therapy ; prevention & control ; Diabetes Complications ; drug therapy ; prevention & control ; Diabetes Mellitus ; pathology ; Flavonoids ; analysis ; Lens, Crystalline ; enzymology ; Phenols ; analysis ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Violaceae ; metabolism

BACKGROUNDOphthalmic gel has been developed to increase the drug concentration in aqueous humor and to retard the loss of drug from the conjunctival sac. The research was to compare the drug concentration in aqueous humor of cataract patients administered 0.3% gatifloxacin ophthalmic gel with that in patients administered 0.3% gatifloxacin ophthalmic solution.

METHODSNinety-six patients with cataract (96 eyes) were randomly assigned to 8 groups. The patients in groups 1-4 received topical gatifloxacin 0.3% ophthalmic gel and those in groups 5-8 received gatifloxacin 0.3% ophthalmic solution. The dose regimen was 1 drop, 4 times a day for 3 consecutive days prior to cataract surgery. On the day of surgery, 1 drop was applied at 15, 30, 60 or 120 minutes before commencement of cataract surgery in groups 1 and 5, groups 2 and 6, groups 3 and 7, and groups 4 and 8, respectively. Aqueous humor was extracted during the cataract surgery for the analysis of gatifloxacin concentration..

RESULTSThe concentrations of gatifloxacin in aqueous humor were (0.24 +/- 0.25) microg/ml, (1.11 +/- 0.74) microg/ml, (2.32 +/- 2.01) microg/ml and (1.85 +/- 1.14) microg/ml in groups 1 to 4, and (0.16 +/- 0.25) microg/ml, (0.31 +/- 0.24) microg/ml, (0.75 +/- 0.28) microg/ml and (0.33 +/- 0.22) microg/ml in groups 5 to 8, respectively. Patients receiving gatifloxacin ophthalmic gel showed greater mean values of gatifloxacin concentration in aqueous humor than those receiving gatifloxacin solution, and such differences were significant with P < 0.05 for all comparisons except that between groups 1 and 5.

CONCLUSIONTopical gatifloxacin ophthalmic gel can attain significantly greater drug concentrations in human aqueous humor than gatifloxacin ophthalmic solution.

Aged ; Aged, 80 and over ; Anti-Infective Agents ; administration & dosage ; analysis ; pharmacokinetics ; therapeutic use ; Aqueous Humor ; metabolism ; Cataract ; drug therapy ; metabolism ; Chromatography, High Pressure Liquid ; Female ; Fluoroquinolones ; administration & dosage ; analysis ; pharmacokinetics ; therapeutic use ; Humans ; Male ; Middle Aged ; Tandem Mass Spectrometry

PURPOSE: To investigate the effect of catechin on apoptotic cell death in the lens epithelium of rats with cataract. METHODS: Cataract was induced by intraperitoneal injection of 100 mg/kg N-methyl-N-nitrosourea (MNU) to ten day-old Sprague-Dawley rats. The neonatal rats were randomly divided into five groups (n=15 in each group): a control group, and four cataract-induction groups, treated with either 0, 50, 100, 200 mg/kg catechin. We performed slit-lamp biomicroscopic analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, Western-blot for Bcl-2 and Bax, and immunohistochemistry for caspase-3. RESULTS: Apoptotic cell death in lens epithelial cells that increased following cataract formation in rats was suppressed by cathechin. CONCLUSIONS: Catechin inhibited cataract-induced apoptotic cell death in the lens epithelium and may prove useful for the prevention of cataract progression.
Analysis of Variance ; Animals ; Animals, Newborn ; Apoptosis/*drug effects ; Blotting, Western ; Caspase 3/metabolism ; Cataract/chemically induced/*drug therapy ; Catechin/*pharmacology ; Immunoenzyme Techniques ; In Situ Nick-End Labeling ; Lens, Crystalline/*drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Epalrestat is the unique aldose reductase inhibitor on the market, which was mainly used for the diabetic neuropathy. Lenses osmotic expansion could be induced by galactose to mimic the pathological process of diabetic cataract in vitro. In present study, we mainly investigated whether epalrestat possesses inhibitory effect on the lens osmotic expansion. The results indicated that epalrestat could not only markedly inhibit rat lens osmotic expansion in vitro, but also significantly reduced the high expression of the osmotic expansion-related genes such as AR and AQP1 in mRNA and protein levels. The findings may provide an important reference to epalrestat in the clinical application for the treatment of diabetic cataract.
Aldehyde Reductase ; antagonists & inhibitors ; biosynthesis ; genetics ; Animals ; Aquaporin 1 ; genetics ; metabolism ; Cataract ; etiology ; metabolism ; pathology ; Diabetes Mellitus, Experimental ; complications ; Enzyme Inhibitors ; pharmacology ; Galactose ; antagonists & inhibitors ; Lens, Crystalline ; drug effects ; metabolism ; pathology ; Male ; Osmosis ; drug effects ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rhodanine ; analogs & derivatives ; pharmacology ; Thiazolidines ; pharmacology

OBJECTIVETo study the preventing effects of procyanidins (PC) on selenite cataract in rats and the time-effect relationship.

METHODForty five SD rats were divided into three groups: control, model and experiment groups. The rats in the experiment group were fed additionally with the PC by 80 mg x kg(-1) when they were supplied the equal selenite with the model group. Five rats of each group were regularly sacrificed by bleeding from femoral artery at sixth, eleventh, sixteenth day and the level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of all lenses was measured.

RESULTCompared with the model group, the level of the MDA in the experiment group at the eleventh day and the sixteenth day greatly decreased (P < 0.01). At the sixteenth day the level of the SOD and GSH-Px had an increase (P < 0.01), which showed its anti-oxygenation.

CONCLUSIONPC indicated the obvious inhibition in the development of the rat cataract. The treatment period was recommended at least for fifteen days.

Animals ; Cataract ; chemically induced ; prevention & control ; Female ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Proanthocyanidins ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium Selenite ; pharmacology ; Superoxide Dismutase ; metabolism

This study was undertaken to isolate and characterize the protease activity of human eye lens sample of mature and hyper mature cataract. Samples were collected just after surgery of the cataract lens and were stored at -20 degrees C. The total protein extract was isolated from 5 samples in each case (mature and hyper mature cataract) and clear supernatant obtained after centrifugation was used as an enzyme source. The optimum pH for the proteases of mature cataract was 7.5 while the proteases of hyper mature cataract were recorded for maximum activity at pH 5.5 and 7.5. The optimum temperature for both enzyme sources was 50 degrees C. Effect of different metal ions such as potassium, lead, silver, zinc and borate was studied. In each case protease activity was increased. Reducing agent e.g. beta mercaptoethanol also caused an increase in activity indicating the involvement of sulfhydryl groups. Protease activity was also located on agar plates.
Aged ; Amino Acids ; metabolism ; Cataract ; enzymology ; pathology ; Endopeptidases ; metabolism ; Enzyme Activation ; drug effects ; Humans ; Hydrogen-Ion Concentration ; Ions ; chemistry ; Metals ; chemistry ; pharmacology ; Middle Aged ; Substrate Specificity

To investigate if the surface modification of intraocular lens (IOL) is efficient in the prevention of posterior capsular opacification (PCO), the acrylic surface of intraocular lens (Acrysof(R)) was polymerized with polyethylene glycol (PEG-IOL). The human lens epithelial cells (1x10(4) cells/mL) were inoculated on PEG grafted or unmodified acrylic lenses for the control. The adherent cells on each IOL surface were trypsinized and counted. The every PEG-IOL was implanted in 20 New Zealand rabbits after removal of crystalline lens. The formations of PCO were checked serially through retroilluminated digital photography, and the severity scores were calculated using POCOman(R). The cell adherence patterns on each IOL were examined by scanning electron microscopy. As a result, the mean number of adherent cells of PEG-IOL (3.2+/-1.1x10(3)) tended to be smaller than that of the acrylic controls (3.6+/-1.9x10(3)) without a statistical significance (p=0.73). However, the mean severity of PCO formation in PEG-IOL was significantly lower than that in the control during the third to sixth weeks after surgery. Scanning electron microscopy revealed that the more patch-like cells were found firmly attached to the IOL surface in control than in the PEG-IOL. Conclusively, PEG polymerization to the acrylic IOL would possibly lessen the formation of PCO after cataract removal.
Acrylic Resins/chemistry ; Biocompatible Materials ; Cataract/metabolism/*therapy ; Cell Adhesion ; Humans ; Lens Implantation, Intraocular/*methods ; Lens, Crystalline/cytology/ultrastructure ; Microscopy, Electron, Scanning ; Polyethylene Glycols/*chemistry/metabolism ; Time Factors