Mitigation of lens opacification by a functional food in a diabetic rodent model.

The current study was designed to test a functional food (FF) mixture containing aldose reductase inhibitors and antiglycation bioactive compounds for suppressing the onset and progression of cataracts in a diabetic rat model. Two-month-old Sprague Dawley rats were grouped as control (C), diabetes untreated (D), and diabetic rats treated with FF at two doses (FF1 = 1.35 g and FF2 = 6.25 g/100g of diet). Diabetes was induced by a single injection of streptozotocin. The FF is a mixture of amla, turmeric, black pepper, cinnamon, ginger, and fenugreek added to the rodent diet. The status of cataracts was monitored weekly by a slit lamp examination for 20 weeks, after which animals were sacrificed to collect eye lenses. Feeding FF1 and FF2 to diabetic rats yielded a significant anti-hyperglycaemic effect and marginally prevented body weight loss. FF delayed cataract progression, and FF2 showed better efficacy than FF1. FF prevented the loss of lens crystallins and their insolubilization in diabetic rats. The antioxidant potential of FF was evident with the lowered protein carbonyls, lipid peroxidation, and prevention of altered antioxidant enzyme activities induced by diabetes. These studies demonstrate the efficacy of plant-derived dietary supplements against the onset and progression of cataracts in a well-established rat model of diabetic eye disease.

[Mechanism of gigantol in transmembrane transport in human lens epithelial cells].

Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.

Spectral-Domain OCT Lens Meridian Position as a Metric to Estimate Postoperative Anatomical Lens Position.

PURPOSE: To evaluate the prediction of postoperative anatomical lens position (ALP) using intraoperative spectral-domain optical coherence tomography (SD-OCT) lens anatomy metrics in patients who underwent femtosecond laser-assisted cataract surgery. METHODS: Intraoperative SD-OCT (Catalys; Johnson & Johnson Vision) and postoperative optical biometry (IOLMaster 700; Carl Zeiss Meditec AG) were used to assess anterior segment landmarks, including lens thickness, lens volume, anterior chamber depth, lens meridian position (LMP), and measured ALP. LMP was defined as the distance from the corneal epithelium to the lens equator, and ALP was defined as the distance from the corneal epithelium to the IOL surface. Eyes were divided into groups according to axial length (> 22.5 mm, 22.5 to 24.5 mm, and > 24.5 mm) and IOL type (Tecnis ZCB00 [Johnson & Johnson Vision]; AcrySof SN-60WF [Alcon Laboratories, Inc], or enVista MX60E [Bausch & Lomb]) to further analyze the correlation between LMP and ALP. Theoretical effective lens position was back-calculated using a specific formula. Primary outcome was correlation between postoperative measured ALP and LMP. RESULTS: A total of 97 eyes were included in this study. Linear regression analysis displayed a statistically significant correlation between intraoperative LMP and postoperative ALP (R2 = 0.522; P < .01). No statistically significant correlation was observed between LMP and lens thickness (R2 = 0.039; P = .06) or between ALP and lens thickness (R2 = 0.02; P = .992). The greatest predictor for ALP was LMP (ß = 0.766, P < .001; R2 = 0.523). CONCLUSIONS: Intraoperative SD-OCT-measured LMP correlated better than anterior chamber depth and axial length to postoperative ALP. Further studies are necessary to analyze the impact of preoperative or intraoperative LMP measurements on postoperative refractive outcomes. [J Refract Surg. 2023;39(3):165-170.].

Nanofluorescence Probe in Detection of miR-187 and Its Correlation with Oxidative Stress Response in Cataracts.

Objective: This study aimed to explore the sensitivity of a nano-fluorescent probe in the detection of miR-187 and the correlation of miR-187 with cataract oxidative stress response. Method: We selected 24 patients with cataracts and 24 healthy people from January 2019 to January 2021 to undergo a nano-fluorescence miR-187 test. We divided cultured human lens epithelial cells (HLECs) into 3 groups: control, overexpressed miR-187 and miR-187 silence, in order to investigate the intracellular oxidative stress response, and the activity and apoptosis of HLECs in the state of oxidative stress. Results: The expression of miR-187 increased significantly in patients with cataracts, and the overexpression of miR-187 promoted the oxidative stress response in HLECs. In the oxidative stress environment simulated by hydrogen peroxide, the downregulation of miR-187 can significantly increase HLEC activity and reduce its apoptosis. In order to further study the role of miR-187 in cataract progression, cataract mouse models were injected with miR-187 mimic and inhibitor. The results showed that miR-187-inhibitor can inhibit the progression of cataracts. Conclusion: The expression of miR-187 is significantly related to cataract prognosis, and down regulation of miR-187 expression has significant antioxidation capacity and can reduce HLEC apoptosis.

Levels of Trace Elements in the Lens, Aqueous Humour, and Plasma of Cataractous Patients-A Narrative Review.

Cataracts are one of the most common causes of effective vision loss. Although most cases of cataracts are related to the ageing process, identifying modifiable risk factors can prevent their onset or progression. Many studies have suggested that micro and macroelement levels, not only in blood serum but also in the lens and aqueous humour, may affect the risk of the occurrence and severity of cataracts. This systematic review aims to summarise existing scientific reports concerning the importance of trace elements in cataractogenesis. Many authors have pointed out elevated or decreased levels of particular elements in distinct ocular compartments. However, it is not known if these alterations directly affect the increased risk of cataract occurrence. Further studies are needed to show whether changes in the levels of these elements are correlated with cataract severity and type. Such information would be useful for determining specific recommendations for micronutrient supplementation in preventing cataractogenesis.

Capsella bursa-pastoris (L.) Medic. extract alleviate cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Capsella bursa-pastoris (L.) Medic. (CBP) is a cruciferous plant valuable in reducing fever, improving eyesight and calming the liver. This herb was recorded in the Compendium of Materia Medica for cataract treatment. AIM OF THE STUDY: To determine the effects and mechanism of CBP on cataract prevention and treatment using a selenite cataract model. MATERIALS AND METHODS: The main compounds in CBP extract were analyzed by UPLC, 1H-NMR and 13C-NMR spectroscopic techniques. Flavonoids formed a significant proportion of its compounds, thus necessitating an evaluation of their inhibitory effects on the development of cataract using a selenite cataract model. The protective effects of CBP flavonoids (CBPF) against oxidative damage and the modulation of mitochondrial apoptotic pathway were subsequently verified on H2O2-treated SRA01/04 lens epithelial cells. RESULTS: CBPF significantly alleviated the development of cataract by decreasing the MDA level and increasing the GSH-Px and SOD levels in the lens. It also inhibited H2O2-induced apoptosis in SRA01/04 cells, increased the expression of Bcl-2 protein and decreased the expressions of Caspase-3 and Bax proteins. CONCLUSION: CBPF exerts a significant preventive effect on cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells. It is thus a potent traditional Chinese medicine (TCM) whose application should be further developed for the clinical treatment of cataract.

Hyperbaric oxygen as a model of lens aging in the bovine lens: The effects on lens biochemistry, physiology and optics.

Age related nuclear (ARN) cataracts in humans take years to form and so experimental models have been developed to mimic the process in animals as a means of better understanding the etiology of nuclear cataracts in humans. A major limitation with these animal models is that many of the biochemical and physiological changes are not typical of that seen in human ARN cataract. In this review, we highlight the work of Frank Giblin and colleagues who established an in vivo animal model that replicates many of the changes observed in human ARN cataract. This model involves exposing aged guinea pigs to hyperbaric oxygen (HBO), which by causing the depletion of the antioxidant glutathione (GSH) specifically in the lens nucleus, produces oxidative changes to nuclear proteins, nuclear light scattering and a myopic shift in lens power that mimics the change that often precedes cataract development in humans. However, this model involves multiple HBO treatments per week, with sometimes up to a total of 100 treatments, spanning up to eight months, which is both costly and time consuming. To address these issues, Giblin developed an in vitro model that used rabbit lenses exposed to HBO for several hours which was subsequently shown to replicate many of the changes observed in human ARN cataract. These experiments suggest that HBO treatment of in vitro animal lenses may serve as a more economical and efficient model to study the development of cataract. Inspired by these experiments, we investigated whether exposure of young bovine lenses to HBO for 15 h could also serve as a suitable acute model of ARN cataract. We found that while this model is able to exhibit some of the biochemical and physiological changes associated with ARN cataract, the decrease in lens power we observed was more characteristic of the hyperopic shift in refraction associated with ageing. Future work will investigate whether HBO treatment to age the bovine lens in combination with an oxidative stressor such as UV light will induce refractive changes more closely associated with human ARN cataract. This will be important as developing an animal model that replicates the changes to lens biochemistry, physiology and optics observed in human ARN cataracts is urgently required to facilitate the identification and testing of anti-cataract therapies that are effective in humans.

Anti-cataract effects of Dajizhi (Euphorbium) eye drops on selenite-induced cataracts in rat.

OBJECTIVE: To evaluate the effects of Dajizhi (Euphorbium) on selenite-induced cataracts. METHODS: Wistar rat pups were divided into 9 groups. Rats in group 1 were subcutaneously injected with saline, and rats in the other groups were injected with sodium-selenite. Every right eye was treated with 5 µL eye drops 3 times per day, and the left eye received no treatment. The eyes of rats in group 3 were treated with pirenoxine; rats in groups 4, 5, 6, 7, 8 and 9 were respectively treated with Dajizhi (Euphorbium) (25 mg/mL), Dajizhi (Euphorbium) (5 mg/mL), Dajizhi (Euphorbium) methanol extract (25 mg/mL), Dajizhi (Euphorbium) methanol extract (5 mg/mL), euphol (25 mg/mL), euphol (5 mg/mL). Cataracts were observed by a slit lamp before and after treatment. Electroretinograms were acquired at set intervals. The morphological changes of the rat eyes were observed in vitro, and the levels of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in the lenses and aqueous humour were estimated at set intervals. RESULTS: Slit lamp examination showed decreased degrees of cataracts after administration of the different treatments. Morphological comparison showed that Dajizhi (Euphorbium) can reduce the turbidity of the lenses, meaning that Dajizhi (Euphorbium) has the anti-cataract effects. Low-concentration of Dajizhi (Euphorbium), its methanol extract and euphol treatment prevented the b-wave amplitudes of the electroretinograms from falling. Euphorbium treatment significantly restored GSH-Px and SOD levels in the lenses and aqueous humour, especially after 10 and 25 d of administration. Euphorbium may help lenses fight oxidative stress caused by selenite. CONCLUSION: The administration of Dajizhi (Euphorbium) can inhibit selenite-induced cataracts.

Anti-cataract effects of coconut water in vivo and in vitro.

OBJECTIVE: To determine the anti-cataract effects of coconut water (CW) in vivo and in vitro, and to explore the potential pathogenic mechanism. METHODS: In this study, 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (CO), diabetic (DM), diabetic treated with CW (DM + CW), and diabetic treated with Glibenclamide (DM + Gli). Except for the CO group, in the other three groups, intraperitoneal injection of STZ (60 mg/kg) was conducted to establish diabetic models. The experiment was conducted for 20 weeks. The slit-lamp examination was undertaken during the period of experiment (20 weeks), and then, all rats were sacrificed. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the left lens were measured by using biochemical assays. The right lens was used for pathological analysis. The rat lens epithelial cells (LECs) were cultured in vitro and the subcultured cell were divided into four groups, namely the normal glucose group (5 mmol /L glucose, Group I), the high glucose group (40 mmol/L glucose, Group II), high glucose +5% CW group (Group III), and high glucose +10% CW group (Group IV). LECs were cultured under the conditions as described above for 48 h. Cell proliferation and the morphological changes were observed with interted phase contrast microscope.The level of cell apoptosis was determined by flow cytometry. the level of SOD, MDA and GSH-Px were also detected. RESULTS: The lens opacity index decreased in diabetic rats, and LECs apoptosis ratio also decreased in high glucose environments that received CW. Under treatment with CW, reduced MDA level and elevated activities of SOD and GSH-Px were detected, both in vivo and in vitro experiments. The increased severity of cataract and LECs apoptosis were noted in diabetic rats that received normal water, while CW markedly mitigated the enhanced cataract severity and the reduction of LECs induced by diabetes mellitus. CONCLUSION: CW is a functional food that can protect the lens from diabetic cataract. The possible underlying mechanism may be partly explained via the decreased oxidative stress in lens. However, further research needs to be conducted to indicate the pathogenic mechanism of anti-diabetic effects of CW.

Taurine supplementation protects lens against glutathione depletion.

OBJECTIVE: Cataract which is defined as opacification of eye lens forms approximately 40% of total blindness causes all through the world. Age is the biggest risk factor for cataracts and oxidative stress is known to be one of the most important factors causing cataract formation. Age-related nuclear cataract (ARN) is associated with a loss of glutathione in the center of the lens. Taurine is an important antioxidant in lens tissue. Although, there is a high amount of taurine in lenses in early life, its concentration declines with age. In this study, we aimed to investigate the effects of supplemental taurine in lens tissues in an in vivo oxidative stress model which is induced by glutathione depletion to mimic ARN. MATERIALS AND METHODS: Glutathione depletion was induced in rabbits subcutaneously with l-Buthionine -(S,R)-sulfoximine (BSO)- a glutathione inhibitor and the rabbits were treated with taurine. Total GSH, reduced GSH, GSH/GSSG ratio and MDA levels were measured. RESULTS: BSO lowered the reduced GSH and total GSH levels and GSH/GSSG ratio. Taurine reversed these effects. On the other hand, BSO enhanced MDA level which is normalized by taurine. CONCLUSIONS: These findings suggest that glutathione depletion with BSO may be a useful model to mimic ARN and dietary intake of taurine, may have an important role in decelerating the process of cataract formation.

Role of Choline in Ocular Diseases.

Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of acetylcholine, a neurotransmitter of the parasympathetic nervous system, and it is involved in the production and secretion of tears by the lacrimal glands. It also contributes to the stability of the cells and tears on the ocular surface and is involved in retinal development and differentiation. Choline deficiency is associated with retinal hemorrhage, glaucoma, and dry eye syndrome. Choline supplementation may be effective for treating these diseases.

Determination of Afzelin and Astragalin from Lespedeza cuneata on Aldose Reductase Inhibition.

The bioactive chemicals in L. cuneata were investigated by repeated column chromatography and their effect on aldose reductase (AR), obtained from rat lenses, was examined. Results showed that the ethyl acetate and n-butanol fractions of L. cuneata exhibited potential inhibitory effect against AR with IC50 values of 0.57 and 0.49 µg/mL, respectively. Phytochemical analysis of these two fractions resulted in the isolation of five flavonoids namely, acacetin (1), afzelin (2), astragalin (3), kaempferol (4) and scutellarein 7-O-glucoside (5). The AR inhibitory effect of compounds 1-5 was explored; compounds 2, 3 and 5 showed potential AR-inhibitory effects with IC50 values of 2.20, 1.91 and 12.87 µM, respectively. Quantitative analysis of afzelin (2) and astragalin (3) in L. cuneata by high performance liquid chromatography with ultraviolet detection revealed its content to be 0.722-11.828 and 2.054-7.006 mg/g, respectively. Overall, this study showed that L. cuneata is rich in flavonoids with promising AR-inhibitory activities, which can be utilized for the development of natural therapies for treating and managing diabetic complications.

Curcumin Has Protective Effect on the Eye Lens Against Arsenic Toxicity.

Arsenic is a highly carcinogenic environmental contaminant. Curcumin, the bioactive component of turmeric, exhibits therapeutic efficacy against several chronic inflammatory and infectious diseases. The present study was carried out to investigate the impact of arsenic on eye lens and evaluate the ameliorative potential of curcumin against arsenic toxicity. Gene expression analysis of α, ß, and γ-crystallins and fatty acid profile of lens tissues of arsenic-exposed Labeo rohita was examined and the protective effect of curcumin as diet supplement was evaluated. Curcumin-supplemented diet was prepared at 1.5% and 3% and fed to four groups of fish for 7 days prior to arsenic exposure (at 5 ppm and 15 ppm) for 15 days. Gene expression analysis showed downregulation of α and ß-crystallins in the eye lens of arsenic-exposed groups (fed basal diet), whereas the groups fed a curcumin-supplemented diet showed insignificant alterations. Similarly, fatty acid fingerprint of lens lipids arsenic-exposed group exhibited reduction in saturated fatty acid and docosahexaenoic acid (DHA) content. However, in 3% curcumin-supplemented diet-fed and arsenic exposed group group, fatty acid profile remained unchanged. Interestingly, concentration of one non-fatty acid, an antioxidant compound (phenol 2,4-bis 1,1 dimethyl; PD) that was identified in the GC-MS fingerprinting through NIST library (version 2.2, 2014), decreased in response to arsenic exposure which was restored to normal level in curcumin-supplemented groups proving the therapeutic potential of curcumin. The findings of the study suggest that curcumin has a protective effect on eye lens against arsenic toxicity.

Single high-dose peroral caffeine intake inhibits ultraviolet radiation-induced apoptosis in human lens epithelial cells in vitro.

PURPOSE: The aim of the present study was to determine whether caffeine concentrations in human lens epithelial cells (LECs) achieved from acute peroral caffeine intake inhibit ultraviolet radiation-induced apoptosis in vitro. METHODS: Patients were planned for cataract surgery of both eyes with a caffeine abstinence of 2 weeks in total, starting 1 week before surgery of the first eye. The second eye was scheduled 1 week after the first eye. At the day of the second eye surgery, patients were given coffee containing 180 mg caffeine shortly before surgery. Lens capsules including LEC, harvested after capsulorhexis, were transferred to a cell culture dish and immediately exposed to close to threshold ultraviolet radiation (UVR). At 24 hr after UVR exposure, apoptotic LECs were analysed by TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining. RESULTS: TUNEL-positive cells were detected in UVR-exposed lens capsules both after caffeine intake and in controls. The mean difference in TUNEL-positive cells between caffeine intake and contralateral controls (no caffeine) resulted in a 95% CI 15.3 ± 10.4% (degrees of freedom: 16). CONCLUSION: Peroral caffeine consumption significantly decreased UVR-induced apoptosis in LEC supporting epidemiological findings that caffeine delays the onset of cataract.

Role of Blueberry Anthocyanin Extract in the Expression of SIRT1 and NF-κB in Rat Lens Epithelial Cells in Experimentally Induced DM.

PURPOSE: To investigate the mechanism of the protective effects of blueberry anthocyanin extract (BAE) against oxidative stress and the roles of SIRT1 and NF-κB in the pathogenesis of diabetic cataracts. METHODS: Male SD rats were randomly divided into a control group (group A) and an experimental group. The rats in the experimental group were intraperitoneally injected with streptozotocin (STZ) (60 mg/kg). Rats with blood glucose levels ≥16.7 mmol/L were considered to have DM. The rats in the experimental group were subdivided into group B (distilled water by oral gavage: 10 ml/kg/day), group C (5% blueberry anthocyanin extract by oral gavage: 10 ml/kg/day), and group D (15% blueberry anthocyanin extract by oral gavage: 10 ml/kg/day), with 15 rats in each group. At the end of 8 weeks, some biochemical parameters, including the expression of SIRT1 and NF-κB by qRT-PCR and western blotting and the activity of SOD and GSH, were measured in lens epithelial cells (LECs). RESULTS: The lenses of the rats in the control group appeared transparent during the entire 8-week period. Four weeks following STZ injection, cataracts gradually progressed in the experimental rats. SIRT1 expression was upregulated in groups B, C and D compared to the control group. However, the expression of NF-κB decreased in the experimental groups with increasing doses of BAE (p < .05). Our study also showed that the activity of the SOD enzyme and GSH in the LECs of the rats in the experimental group increased with higher doses of BAE. CONCLUSIONS: The results indicated that BAE significantly delayed the progression of diabetic cataracts in rats. These effects may be due to the dose-dependent antioxidant activity of BAE, which is mediated by enhanced SOD and GSH activities, SIRT1 expression and reduced NF-κB expression. Abbreviations: SD rat: Sprague-Dawley rat; BAE: Blueberry anthocyanin extract; LECs: Lens epithelial cells; SOD: Superoxide dismutase; GSH: Glutathione; DM: Diabetes mellitus; SIRT1: Silent information regulator protein-1; STZ: Streptozotocin; PBS: Phosphate-buffered saline.

Ganoderic acid A protects lens epithelial cells from UVB irradiation and delays lens opacity.

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.

Prevention of Diabetic Complications by Walnut Leaf Extract via Changing Aldose Reductase Activity: An Experiment in Diabetic Rat Tissue.

BACKGROUND: Increased activity of aldose reductase (AR) is one of the mechanisms involved in the development of diabetic complications. Inhibiting AR can be a target to prevent diabetes complications. This study is aimed at evaluating the effect of cyclohexane (CH) and ethanol extracts (ET) of walnut leaves on AR activity in the lens and testis of diabetic rats. METHODS: Fifty-six male rats classified into seven groups as control and treatment groups and treated for 30 days. The treatment groups were treated with different concentrations of ET and CH. The diabetic control (DC) group was exposed to streptozotocin. AR activity was measured in the lens and testis. The expression of AR in the testis was evaluated by the immunohistochemistry method. RESULTS: Both extracts significantly reduced the AR activity (ng/mg of tissue protein) in the testis (0.034 ± 0.004, 0.038 ± 0.010, and 0.040 ± 0.007 in the treatment groups vs. 0.075 ± 0.007 in the DC group) and lens (1.66 ± 0.09, 2.70 ± 0.47, and 1.77 ± 0.20 in the treatment groups vs. 6.29 ± 0.48 in the DC group) of the treatment group compared to those of the DC group (P < 0.05). AR expression in the testes of the treatment groups was decreased compared with that of the DC group (P < 0.0001). CONCLUSION: Walnut leaf extracts can reduce the activity and localization of AR in the testes and its activity in the lens of diabetic rats.

Activation of Sirtuin1 by lyceum barbarum polysaccharides in protection against diabetic cataract.

ETHNOPHARMACOLOGICAL RELEVANCE: Lycium barbarum polysaccharide (LBP) extracted from the Lycium barbarum L. has been widely used to improve diabetes and its relative complications. However, the mechanisms have not fully understood. A recent study has demonstrated that LBP upregulates suituin 1 (SIRT1). OBJECTIVE: This study was to define the role of Sirt1 and its downstream signaling pathways in diabetic cataract using in vitro and in vivo models. MATERIALS AND METHODS: Human lens epithelial cell line SRA01/04 cells were cultured under high glucose (HG) medium with treatment of LBP or vehicle. Cell viability, apoptosis, protein and/or mRNA levels of Sirt1, BAX, Bcl-2, active-caspase-3, FOXO1, p27 and acetylated p53 were measured. SIRT1 upregulated- and knocked-down cells were generated and tested in high glucose culture. Diabetes mellitus was induced in rats by streptozotocin injection. Body weight, blood glucose levels, lens transparency and retinal function were assessed and SIRT1, as well as the aforementioned biomarkers were measured using Western blotting and qPCR in the animal lens samples. RESULTS: The results showed that HG decreased cell viability and LBP prevented the decrease. The reduced viability in HG cultured SRA01/04 cells was associated with increased levels of BAX, active caspase 3, FOXO1, p27, and p53 and decreased levels of SIRT1 and Bcl-2. Further experiments using sirt1 gene modulated cells showed that upregulation of Sirt1 improved viability, increase cell division as reflected by an increased proportion of S phase in the cell cycle, reduced the number of apoptotic cell death and suppressed p53 acetylation and caspase 3 activation. Opposite results were observed in SIRT1 knock-down cells. Treating diabetic animals with LBP reduced body weight loss and blood glucose content in diabetic animals. Similarly, LBP hindered the development of cataract in lenses and improved retinal function. The beneficial effect of LBP on diabetic cataract was associated with the supression of p53, caspase 3, FOXO1, BAX, p27 and elevation of SIRT1 and Bcl-2, which were consistent with the in vitro findings. CONCLUSION: Our findings showed that diabetes caused cataract is associated with suppression of SIRT1 and Bcl-2 and activation of other cell death related genes. LBP prevented diabetic cataract in animals by upregulating Sirt1 and Bcl-2 and suppressing cell death related genes.

Lutein plus Water Chestnut (Trapa bispinosa Roxb.) Extract Inhibits the Development of Cataracts and Induces Antioxidant Gene Expression in Lens Epithelial Cells.

Age-related cataract (ARC) is the major cause of blindness worldwide. The most significant factors are the maximal exposure of the eye lens to environmental stressors, including oxidative and glycative load. The administration of antioxidant and antiglycative supplements may reduce the risk of cataract progression. In this study, the effects of lutein (LU) and water chestnut (Trapa bispinosa Roxb.) extract (TBE) on cataracts and the expression of antioxidant-related genes were assessed in Shumiya cataract rats (SCRs). LU+TBE or castor oil (COil) as a control was administered to 6- or 9-week-old cataractous SCRs and noncataractous SCRs via a feeding needle for 3 or 4 weeks. Five-week-old SCRs were provided ad libitum access to solid regular chow containing LU, TBE, LU+TBE, or the same chow without LU and/or TBE for 3 weeks. Lenses from all rats were then extracted and photographed. The right eyes of the rats were processed for histological observation, and the left eyes were used for total RNA extraction from lens epithelial cells (LEC). The mRNA levels of antioxidant proteins, peroxiredoxin 6, and catalase were examined using real-time quantitative polymerase chain reaction. Lens opacity appeared in all cataractous SCRs that began receiving LU+TBE at 9 weeks of age. However, compared to the COil group, lens opacity was decreased in the cataractous LU+TBE SCRs in all experiments. The mRNA expression levels of peroxiredoxin 6 and catalase in LECs of cataractous SCRs and cultured human LECs increased after the administration of LU+TBE. Collectively, our results highlight the anticataract and antioxidative effects of LT+TBE in SCRs. LT+TBE supplementation may, thus, be useful in delaying cataract progression.