Cataract In Rats Research Articles

Impact of Pterostilbene on Lens Epithelial Cells from Cataract Model Rats

Lens epithelial cell (lEC) membrane is one of the pathological process of cataract. Sandalwood stilbene is a kind of non-flavonoid polyphenol extracted from blueberries, grapes and other berries. It is considered as a natural antioxidant through various related mechanisms. This study was to investigate the effect and mechanism of Rosewood astragalus on lEC in oxidative cataract rats, and to provide evidence for clinical cataract treatment. Grouping method: normal control group, model group (H2O2 induced cataract) and Zitan astragalus group. Lens turbidity was observed, LECs was isolated and cultured. MTT assay was used to detect LECs proliferation and Caspase-3 activity was used to detect LECs apoptosis. The expression of NF-κB pathway was analyzed. The activities of superoxide dismutase (SOD), reactive oxygen species (ROS) were detected. The results showed that H2O2 significantly increased lens turbidity, enhanced Caspase-3 activity, inhibited LECs proliferation, increased NF-κB pathway expression, increased ROS activity, and decreased SOD activity (P <0.05). Dansandalus stilbene had the effects of inhibiting NF-κB pathway expression, promoting LECs proliferation, decreasing Caspase-3 activity, decreasing ROS production and increasing SOD activity (P < 0.05). In this study, it is suggested that Rosewood stilbene delaying the oxidation of traumatic cataract by anti-oxidation and apoptosis of LECs, and regulating cell proliferation, inhibiting the expression of NF-κB.

Slit2 Promotes H2O2-Induced Lens Epithelial Cells Oxidative Damage and Age-Related Cataract

Purpose To analyze the role of Slit2 in lens epithelial cell oxidative damage and its underlying mechanism. Methods Human lens epithelial cells (SRA01/04 cells) and rat transparent lens were cultured with H2O2 to establish cell oxidative stress models and rat cataract models. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot assays were employed to detect Slit2 levels within age-related cataracts(ARC) lens anterior capsule samples, rat cataract models, and cell oxidative stress models. In this study, qRT-PCR and Western blot assays were performed to derermine E-cadherin, N-cadherin, occludens1(ZO-1), α-SMA(α‑smooth muscle actin), Bcl-2, Bax, p-AKT, and AKT levels. In addition, Flow cytometry were performed to examine reactive oxygen species (ROS) and cell apoptosis. Cell viability, invasion, and migration were detected by CCK8, Transwell, and Wound healing. Results Increased expression of Slit2 was found in ARC lens anterior capsule samples, H2O2-induced rat cataract models, and Human lens epithelial cells (HLECs) oxidative stress models. H2O2 significantly increased cell apoptosis and ROS generation, also accelerating cell migration, invasion, and epithelial-mesenchymal transition (EMT). In addition, H2O2 treatment repressed AKT phosphorylation and cell viability. Knock-down of Slit2 promoted cell viability and AKT phosphorylation levels, as well as repressed cell invasion, migration, apoptosis, ROS production and EMT. Conclusion Slit2 promoted lens epithelial cells oxidative stress damage via the AKT signalling pathways, providing a novel insight in ARC treatment.

TRB3 Promotes Cataract Progression through Endoplasmic Reticulum Stress-mediated Mitochondrial Dysfunction and Cell Apoptosis.

Cataracts are characterized as a disease affecting lens opacity. Endoplasmic reticulum (ER) stress can cause lens epithelial cell (LEC) dysfunction, affecting normal lens transparency and function, but the role of Tribbles 3 (TRB3), an inducible gene of ER stress, in cataracts is poorly understood. This study explored how TRB3 promotes cataract progression through ER stress. We administered a subcutaneous injection of sodium selenite at a dosage of 3.46 mg/kg to rats to create an animal model of cataracts. Additionally, we exposed rat LEC cells to 0.01 μM tunicamycin (TM) for 24 h to establish a cell model of ER stress. The detection of related genes and proteins was performed via RT‒qPCR and Western blot techniques. Flow cytometry, along with JC-1, TUNEL, and HE staining, was employed to assess damage to cells and lens tissues. This study revealed that TRB3 was abnormally highly expressed in both a cataract rat model and an ER stress cell model. Knocking down TRB3 has a similar effect as treatment with an ER stress inhibitor, effectively reversing the ER stress and apoptosis induced by TM. This effect includes increasing the mitochondrial membrane potential in LEC cells, lowering reactive oxygen species (ROS) levels, increasing ATP production, suppressing the expression of the apoptosis-related proteins Bax and C-caspase-3, increasing Bcl-2 expression, and decreasing apoptosis. Furthermore, TRB3 knockdown improved the pathological conditions of rat lenses and inhibited mitochondrial dysfunction and cell apoptosis to relieve the development of cataracts in rats. Mechanistically, CHOP promotes the expression of TRB3 by binding to the TRB3 promoter, thereby activating ER stress, leading to mitochondrial dysfunction and cell apoptosis in LEC cells and accelerating the development of cataracts. According to our findings, targeting TRB3 expression inhibition could emerge as a novel approach for cataract therapy.

SIRT1 inhibits apoptosis of human lens epithelial cells through suppressing endoplasmic reticulum stress in vitro and in vivo.

To explore the effect of silent information regulator factor 2-related enzyme 1 (SIRT1) on modulating apoptosis of human lens epithelial cells (HLECs) and alleviating lens opacification of rats through suppressing endoplasmic reticulum (ER) stress. HLECs (SRA01/04) were treated with varying concentrations of tunicamycin (TM) for 24h, and the expression of SIRT1 and C/EBP homologous protein (CHOP) was assessed using real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8 (CCK-8) assay, respectively. In the SRA01/04 cell apoptosis model, which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation, the expression levels of SIRT1, CHOP, glucose regulated protein 78 (GRP78), and activating transcription factor 4 (ATF4) were examined. The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid (4-PBA; an ER stress inhibitor) was investigated. In vivo, age-related cataract (ARC) rat models were induced by sodium selenite injection, and the protective role of SIRT1, activated by SRT1720 intraperitoneal injections, was evaluated through morphology observation, hematoxylin and eosin (H&E) staining, Western blotting, and RT-PCR. SIRT1 expression was downregulated in TM-induced SRA01/04 cells. Besides, in SRA01/04 cells, both cell apoptosis and CHOP expression increased with the rising doses of TM. ER stress was stimulated by TM, as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model. Inhibition of SIRT1 by siRNA knockdown increased ER stress activation, whereas SRT1720 treatment had opposite results. 4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis. In vivo, SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models. SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress. These findings suggest a novel strategy for cataract treatment focused on targeting ER stress, highlighting the therapeutic potential of SIRT1 modulation in ARC development.

Potential prophylactic effect of Naringenin loaded liposome eye drops on streptozotocin-induced diabetic cataract in rats

Potential prophylactic effect of Naringenin loaded liposome eye drops on streptozotocin-induced diabetic cataract in rats

Baicalein improves Na2SeO3 induced cataract by enhancing the antioxidant capacity of juvenile Sprague Dawley Rat

Ethnopharmacological relevanceBaicalein (BAI) is the crucial flavonoid component in Scutellaria baicalensis Georgi, possessing biological functions such as anti-oxidant, anti-apoptotic, and anti-inflammatory. However, there is limited intensive pharmacological and mechanistic research on the therapeutic effects of BAI for cataract treatment. Aim of the studyThis study aimed to investigate the effects and mechanisms of BAI on Na2SeO3-induced cataract in juvenile rats. Materials and methodsThe cataract model was established by a single subcutaneous injection of 3.46 mg/kg Na2SeO3 on the back of 10-day-old rats. The BAI (25 mg/kg, 50 mg/kg, 100 mg/kg) was administered to the 8-day-old rats and continued until they reached 30 days of age, and the opacity of the lens was observed using a slit lamp microscope every 3 days. Pathological changes in the lens were observed using hematoxylin-eosin (HE) staining to investigate the effects of BAI on Na2SeO3-induced cataract in rats. The levels of antioxidant substances in rat serum and the lens, as well as the levels of soluble and insoluble proteins in rat lens, were measured by the reagent kit. Furthermore, the mechanism of BAI on Na2SeO3-induced cataract rats was analyzed by network pharmacology, molecular docking, and Western blot. ResultsBAI significantly increased the content of soluble proteins in the lens, mitigated the dense opacity of rat lens and reduced the damage to lens epithelial cells, reduced the levels of malondialdehyde (MDA) in rat serum and lens, increased the levels of total superoxide dismutase (T-SOD) and Glutathione peroxidase (GSH-PX). The improvement effects of BAI on Na2SeO3-induced cataract may related to the mitogen-activated protein kinase (MAPK) and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. ConclusionIn conclusion, this study demonstrated that BAI could mitigate the dense opacity of rat lens in Na2SeO3-induced cataract rats, which may be achieved through the MAPK signaling pathway and the PI3K/AKT signaling pathway.

Transcriptome sequencing and microRNA–mRNA regulatory network construction in the lens from a Na2SeO3-induced Sprague Dawley rat cataract model

BackgroundA sight-threatening, cataract is a common degenerative disease of the ocular lens. This study aimed to explore the regulatory mechanism of age-related cataract (ARC) formation and progression.MethodsCataracts in Sprague Dawley rats were induced by adopting the method that injected selenite subcutaneously in the nape. We performed high-throughput RNA sequencing technology to identify the mRNA and microRNA(miRNA) expression profiles of the capsular membrane of the lens from Na2SeO3-induced and saline-injected Sprague Dawley rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to forecast the regulatory and functional role of mRNAs in cataracts by DAVID and Metascape. The protein–protein interaction(PPI) network of differentially expressed mRNA(DEmRNAs) was built via the STRING. Target miRNAs of hub genes were predicted by miRBD and TargetScan. Furthermore, differentially expressed miRNA(DEmiRNAs) were selected as hub genes’ targets, validated by quantitative real-time polymerase chain reaction(qRT-PCR), and a DEmiRNA-DEmRNA regulatory network was constructed via Cytoscape.ResultIn total, 329 DEmRNAs including 40 upregulated and 289 downregulated genes were identified. Forty seven DEmiRNAs including 29 upregulated and 18 downregulated miRNAs were detected. The DEmRNAs are involved in lens development, visual perception, and aging-related biological processes. A protein–protein interaction network including 274 node genes was constructed to explore the interactions of DEmRNAs. Furthermore, a DEmiRNA-DEmRNA regulatory network related to cataracts was constructed, including 8 hub DEmRNAs, and 8 key DEmiRNAs which were confirmed by qRT-PCR analysis.ConclusionWe identified several differentially expressed genes and established a miRNA-mRNA-regulated network in a Na2SeO3-induced Sprague Dawley rat cataract model. These results may provide novel insights into the clinical treatment of cataracts, and the hub DEmRNAs and key DEmiRNAs could be potential therapeutic targets for ARC.

Gene profiles and mutations in the development of cataracts in the ICR rat model of hereditary cataracts

Cataracts are opacifications of the lens that cause loss of visual acuity and ultimately of eyesight. Age-related cataract develops in most elderly people, but the mechanisms of cataract onset are incompletely understood. The Ihara Cataract Rat (ICR) is an animal model of hereditary cataracts showing cortical opacity that commonly develops prematurely. We identified putative mechanisms of cataract onset in the ICR rat model by measuring gene expression changes before and after cortical cataract development and conducting point mutation analysis. Genes differentially expressed between 4-week-old animals without cortical cataracts and 8–10-week-old animals with cortical cataracts were selected from microarray analysis. Three connections were identified by STRING analysis: (i) Epithelial-Mesenchymal Transition (EMT), including Col1a2, and Pik3r1. (ii) Lens homeostasis, including Aqp5, and Cpm. (iii) Lipid metabolism, including Scd1, Srebf1, and Pnpla3. Subsequently, mutation points were selected by comparing ICR rats with 12 different rats that do not develop cataracts. The apolipoprotein Apoc3 was mutated in ICR rats. Analyses of gene expression changes and point and mutations suggested that abnormalities in EMT or lipid metabolism could contribute to cataract development in ICR rats.

Potential therapeutic effect of Salvia coccinea leaf extract in chronic disorders: Myocardial infarction, cataract, and arthritis in rat

Aqueous extract from Salvia coccinea leaf (AESL) has been shown its unique anti-oxidant effect via Nuclear factor (NF)-kappa (κ)B pathway in human monocytic THP-1 ​cells and pharmacological effect on inflammatory diseases like diabetes in rats. Using AESL, which possess antioxidant activity by scavenging radicals and decreasing oxidative stress, would be a promising strategy for the treatment of other inflammatory disorders like myocardial infarction, arthritis, and cataract. This study was designed to evaluate the ameliorating effects of AESL on isoproterenol (Iso)-induced myocardium infarction (MI), selenite-induced cataractogenesis, and complete Freund's adjuvant-induced arthritis in Wistar rats. In this study, AESL ameliorated pathological changes in Iso-induced MI heart muscles and Electro Cardio Gram pattern, 35–80 ​% protection of the cataractogenesis, and prevented the apoptosis induced by selenite in the rat lens. Both pre and post-treatment of AESL (600 ​mg/kg, bw) showed no swelling of the joint and, 35 days treatment showed significant prevention against bony destruction as depicted by less narrowing of joint spaces and soft tissue swelling when compared with control rats. Oral administration of AESL inhibited the Iso-induced increase in serum and myocardial lipid peroxidation, aspartate transaminase, alanine transaminase, creatine kinase, troponin-I, and troponin-T, and lactate dehydrogenase of myocardium infarction rats. Significant increases in the activity of superoxide dismutase, catalase, glutathione peroxidase, and a reduced level of glutathione, were observed in AESL treated cataract rat lens. The results demonstrate that AESL is useful in, in addition to diabetes, controlling myocardium infarction, cataracts, and arthritis.

Effects of truncations in the N- and C-terminal domains of filensin on filament formation with phakinin in cell-free conditions and cultured cells.

Filensin and phakinin are lens fiber cell-specific proteins that constitute the beaded filaments that are critical for maintaining lens transparency. In the Shumiya cataract rat, filensin 94 kDa undergoes N- and C-terminal proteolytic processing to give a transient 50 kDa fragment and a final 38 kDa fragment, just before opacification. To characterize effects of this processing on filensin function, recombinant proteins representing the two filensin fragments, termed Fil(30-416) and Fil(30-369), respectively, were examined. Fil(30-416) lacks the N-terminal 29 amino acids and the C-terminal 248 amino acids. Fil(30-369) lacks the N-terminal 29 residues and the C-terminal 295 residues. In cell-free assembly characterized by electron microscopy, filensin and Fil(30-416) co-polymerized with phakinin and formed rugged, entangled filaments, whereas Fil(30-369) formed only aggregates. In cultured SW-13 and MCF-7 cells expressing fluorescent fusion proteins, filensin and Fil(30-416) co-polymerized with phakinin and formed cytoplasmic sinuous filaments with different widths, while Fil(30-369) gave aggregates. Therefore, while truncation of the N-terminal 29 amino acids did not affect filament formation, truncation of the C-terminal 295 but not the 248 residues resulted in failure of filament formation. These results indicate that the tail B region (residues 370-416) of rat filensin is essential for filament formation with phakinin. Truncation of the tail B region by proteolytic processing in the cataract rat lens might interfere with beaded filament formation and thereby contribute to opacification.

Astragalin attenuates diabetic cataracts via inhibiting aldose reductase activity in rats.

To investigate the aldose reductase (AR) inhibition capacity of astragalin (AST) against streptozoticin-induced diabetic cataracts (DCs) in rats. Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor (AAH) of pH 7.8 at room temperature with cataract-causing substance (55 mmol/L of galactose) and in vivo studies were performed on rats via induction with streptozotocin. AST was administered at different dose levels and scrutinize for DC activity. In diabetic rats, AST improved the body weight, blood insulin, and glucose as well as the levels of galactitol in a dose-dependent way, other biochemical parameters i.e. inflammatory mediators and cytokines, and also suppress AR activity. The level of the antioxidant parameters such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activity were also altered on a diabetic lens after the administration of the AST. AST protects against lens opacification to avoid cataracts and polyols formation, indicating that it could be used as a potential therapeutic agent for diabetes.

Cellular Localization of FOXO3 Determines Its Role in Cataractogenesis

The transcription factor FOXO3 is a core regulator of cellular homeostasis, stress response, and longevity. The cellular localization of FOXO3 is closely related to its function. Here, we explored the role of FOXO3 in cataract formation. FOXO3 showed nuclear translocation in lens epithelial cells arranged in a single layer on lens capsule tissues from both human cataract and N-methyl-N-nitrosourea (MNU)-induced rat cataract, also in MNU-injured human lens epithelial cell lines (HLECs). FOXO3 knockdown inhibited the MNU-induced increase in expression of genes related to cell cycle arrest (GADD45α and CCNG2) and apoptosis (Bak and TP53). H2 is highly effective in reducing oxidative impairments in nuclear DNA and mitochondria. When we applied H2 to MNU-injured HLECs, FOXO3 underwent cleavage by MAPK1 and translocated into mitochondria, thereby increasing the transcription of oxidative phosphorylation-related genes (MTCO1, MTCO2, MTND1, and MTND6) in HLECs. Furthermore, H2 mediated the translocation of FOXO3 from the nucleus to the mitochondria within the lens epithelial cells of cataract capsule tissues of rats exposed to N-methyl-N-nitrosourea (MNU). This intervention ameliorated MNU-induced cataracts in the rat model. In conclusion, we demonstrated the correlation between the localization of FOXO3 and its function in cataract formation. We also determined that H2 protects HLECs from injury by leading FOXO3 mitochondrial translocation via MAPK1 activation. Mitochondrial FOXO3 can increase mtDNA transcription, stabilize mitochondrial function in HLECs.

Carbon Monoxide Releasing Molecule-3 Alleviates Oxidative Stress and Apoptosis in Selenite-Induced Cataract in Rats via Activating Nrf2/HO-1 Pathway

Purpose This study investigated the protective effect of carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide, on selenite-induced cataract in rats and explore its possible mechanism. Methods Sprague-Dawley rat pups treated with sodium selenite (Na2SeO3) were chosen as the cataract model. Fifty rat pups were randomly divided into 5 groups: Control group, Na2SeO3 (3.46 mg/kg) group, low-dose CORM-3 (8 mg/kg/d) + Na2SeO3 group, high-dose CORM-3 (16 mg/kg/d) + Na2SeO3 group, and inactivated CORM-3 (iCORM-3) (8 mg/kg/d) + Na2SeO3 group. The protective effect of CORM-3 was tested by lens opacity scores, hematoxylin and eosin staining, TdT-mediated dUTP nick-end labeling assay, and enzyme-linked immunosorbent assay. Besides, quantitative real-time PCR and western blotting were used for mechanism validation. Results Na2SeO3 induced nuclear cataract rapidly and stably, and the achievement ratio of Na2SeO3 group was 100%. CORM-3 alleviated lens opacity of selenite-induced cataract and attenuated the morphological changes of the rat lens. The levels of antioxidant enzymes GSH and SOD in rat lens were also increased by CORM-3 treatment. CORM-3 significantly reduced the ratio of apoptotic lens epithelial cells, besides, CORM-3 decreased the expression of Cleaved Caspase-3 and Bax induced by selenite and increased the expression of Bcl-2 in rat lens inhibited by selenite. Moreover, Nrf-2 and HO-1 were upregulated and Keap1 was downregulated after CORM-3 treatment. While iCORM-3 did not exert the same effect as CORM-3. Conclusions Exogenous CO released from CORM-3 alleviates oxidative stress and apoptosis in selenite-induced rat cataract via activating Nrf2/HO-1 pathway. CORM-3 may serve as a promising preventive and therapeutic strategy for cataract.

Characterization of a Novel Gja8 (Cx50) Mutation in a New Cataract Rat Model.

To describe a novel spontaneous cataract inbred strain isolated from large-scale breeding SD rats, identify the responsible gene mutation, and understand how this mutation affects lens function. Exome sequencing of 12 cataract-associated genes was performed in the affected and healthy relatives. Sequences of rat wild-type or mutant gap junction protein alpha 8 gene (Gja8) were transfected into cells. The expression level of protein was assayed by Western blot analysis. Subcellular localization of connexin 50 (Cx50) was analyzed in confocal fluorescent images. Wound-healing, 5-ethynyl-2'-deoxyuridine incorporation, and attachment assay were performed to characterize the cell migration, proliferation and adhesion. The abnormality was found to be inheritable in an autosomal semi-dominant pattern through different mating patterns. We found a G to T transversion at codon 655 in Gja8, leading to a substitution of valine by phenylalanine (p.V219F). Gja8V219F/+ heterozygotes expressed nuclear cataract while Gja8V219F/V219F homozygotes manifested microphthalmia in addition to cataract. Histology revealed fiber disorders and loss of organelle-free zone in the mutant lens. Cx50V219F altered its location in HeLa cells and inhibited the proliferation, migration and adhesion abilities of HLEB3 cells. The mutation also reduced the expression of focal adhesion kinase and its phosphorylation. The c.655G>T mutation (p.V219F) is a novel mutation in Gja8, inducing semi-dominant nuclear cataracts in a new spontaneous cataract rat model. The p.V219F mutation altered Cx50 distribution, inhibited lens epithelial cell proliferation, migration, and adhesion, and disrupted fiber cell differentiation. As a consequence, the nuclear cataract and small lens formed.

Gold Nanoparticles Encapsulated Resveratrol as an Anti-Aging Agent to Delay Cataract Development.

Nanoparticle-based drug delivery systems, which can overcome the challenges associated with poor aqueous solubility and other harmful side effects of drugs, display potent applications in cataract treatment. Herein, we designed a nanosystem of gold nanoparticles containing resveratrol (RGNPs) as an anti-aging agent to delay cataracts. The spherical RGNPs had a superior ability to inhibit hydrogen peroxide-mediated oxidative stress damage, including reactive oxygen species (ROS) production, malondialdehyde (MDA) generation, and glutathione (GSH) consumption in the lens epithelial cells. Additionally, the present data showed that RGNPs could delay cellular senescence induced by oxidative stress by decreasing the protein levels of p16 and p21, reducing the ratio of BAX/BCL-2 and the senescence-associated secretory phenotype (SASP) in vitro. Moreover, the RGNPs could also clearly relieve sodium selenite-induced lens opacity in a rat cataract model. Our data indicated that cell senescence was reduced and cataracts were delayed upon treatment with RGNPs through activating the Sirt1/Nrf2 signaling pathway. Our findings suggested that RGNPs could serve as an anti-aging ingredient, highlighting their potential to delay cataract development.

Reduction in Lens Epithelial Cell Senescence Burden through Dasatinib plus Quercetin or Rapamycin Alleviates D-Galactose-Induced Cataract Progression

Senescent cells accumulate in aged organisms and promote the progression of age-related diseases including cataracts. Therefore, we aimed to study the therapeutic effects of senescence-targeting drugs on cataracts. In this study, a 28-day D-galactose-induced cataract rat model was used. The opacity index, a grading based on slit-lamp observations, was used to assess lens cloudiness. Furthermore, the average lens density (ALD), lens density standard deviation (LDSD), and maximum lens density (MLD) obtained from Scheimpflug images were used to assess lens transparency. Immunohistochemical stainings for p16 and γH2AX were used as hallmarks of senescence. We treated rat cataract models with the senolytic drug combination dasatinib plus quercetin (D+Q) and senescence-associated secretory phenotype (SASP) inhibitors. In comparison to control lenses, D-galactose-induced cataract lenses showed a higher opacity index, ALD, LDSD, and MLD values, as well as accumulation of senescent lens epithelial cells (LECs). After D+Q treatment, ALD, LDSD, and MLD values on day 21 were significantly lower than those of vehicle-treated model rats. The expression levels of p16 and γH2AX were also reduced after D+Q administration. In addition, the SASP inhibitor rapamycin decreased the opacity index, ALD, LDSD, and MLD values on day 21. In conclusion, D+Q alleviated D-galactose-induced cataract progression by reducing the senescent LEC burden in the early stage of cataract.

Влияние ожирения на развитие инсулинорезистентности и окислительного стресса в эксперименте

Purpose. To study influence of abdominal obesity on the formation of peripheral insulin resistance and development of oxidative stress in rats. Materials and methods. Diabetes was developed in 90 white male rats and nonporous females of the Wistar line weighing 80–120 g. In the first group of rats, diabetes mellitus was induced by a single intraperitoneal injection of a 2.5% solution of the antibiotic streptozotocin at a dose of 60 mg/kg of animal weight during a 24–48-hours fasting. In the second group, newborn rats were given a 2.5% solution of streptozotocin once at a dose of 60 mg/kg of body weight, while these rats received a diet enriched with lipids. The composition of the diet included: 8% protein, 30% fat, 62% carbohydrates. The control group received an equivalent amount of saline. The dynamics of carbohydrate and lipid metabolism was assessed. Results. In rats with type 2 diabetes mellitus (DM2) with abdominal obesity and DM2 without obesity structural and functional disorders developed in the membranes of erythrocytes and eye lens fibers, which correlate with indicators of glucose-insulin homeostasis and the level of lipid peroxidation. However, in rats with DM2 and abdominal obesity, the changes in the studied parameters were more significant. Conclusion. Streptozotocin-induced diabetes in obese rats, along with dyslipidemia, leads to the formation of insulin resistance, as evidenced by an increase in the degree of hyperglycemia, a decrease in the activity of insulin receptors and glucose uptake by cells against the background of the development of oxidative stress. The initiating factor of eye lens clouding in cataracts in rats with DM and obesity is apparently a shift in osmolarity in the cells of lens fiber membranes because of the accumulation of insoluble forms of sorbitol and fructose in them. Key words: diabetes mellitus; obesity; streptozotocin; antioxidants; insulin receptors; diabetic cataract; senile cataract

17β-Estradiol Inhibits Oxidative Damage in Cataracts Rats via NOTCH1 Signaling

This study assesses the effect of 17β-estradiol on oxidative damage and NOTCH1 levels in cataract rats. 45 SD rats, aged 8–12 weeks old and weighted 225–312 g were assigned into healthy group, cataract group, and treatment group with n = 15 in each group followed by analysis of the pathological morphology of rat lens by HE staining, cell apoptosis by flow cytometry, and the degree of turbidity under a microscope. Meanwhile, MDA and SOD levels were measured and NOTCH1, p53 and BAX expressions was detected by PT-PCR. The Healthy group rats showed complete and orderly lens structure, whereas, the cataract group showed disorganized and distributed loosely lens, with the formation of vacuoles and the rupture and degradation of fibrocells. In the treatment group, the lens epithelial cells were orderly and evenly distributed, and the vacuoles were significantly reduced. The apoptotic rate of lens epithelial cells in healthy group (1.79±0.11)% was significantly lower than that in cataract group (15.22±1.17)% (P < 0.05), which showed significantly higher apoptotic rate than treatment group (6.31±1.12)% (P < 0.05). The degree of eye turbidity was increased in cataract group and reduced in treatment group compared with that in healthy group (P < 0.05). In addition, cataract group showed significantly reduced SOD and increased MDA level groups along with upregulated Notch1, p53 and Bax (P < 0.05). However, treatment group showed significantly increased SOD, decreased MDA and downregulated Notch1, p53 and Bax. In conclusion, 17β-estradiol reduces the apoptosis rate of lens epithelial cells in cataract rats by reducing NOTCH1 level, thereby enhancing the ability to resist oxidative damage.

Biological Activities of Passion Fruit (Passiflora edulis) in Impediment of Alloxan Induced Cataract in Rats

Biological Activities of Passion Fruit (Passiflora edulis) in Impediment of Alloxan Induced Cataract in Rats

The protective effect of pomegranate peel aqueous extract on selenite-induced cataract in rats.

The present study was performed to evaluate the preventive effect of pomegranate peel extract on sodium-induced cataract in rats. Sprague-Dawley suckling male rats were divided into four groups: group C: rats received no treatment, group P: rats received pomegranate peel aqueous extract (PPE) orally, group Se: rats received an injection of sodium selenite, group Se + P: rats received PPE and sodium selenite concomitantly. After 4 weeks, rats were sacrificed, and their lenses were homogenized and evaluated for biochemical parameters and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the Se group, developed cataract with significant lens opacity was observed. Other changes in enzymatic and non-enzymatic antioxidants, oxidative parameters, solubility of proteins, in NO and Ca levels and the electrophoresis pattern of proteins were observed in lenses of the Se group compared to control groups. After the preventive administration of PPE, most of these parameters were normalized due to antioxidant and anti-inflammatory activities of the extract. PRACTICAL APPLICATIONS: Cataract is one of the leading causes of vision impairment among the elderly, and surgery is the major therapeutic step taken to cure it. However, surgery has its limitations and complications. Therefore, prevention of cataract development, especially in high-risk individuals, can be better than cure. Pomegranate peel extract has a high potential to prevent cataract in these people.