[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.

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.

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.

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.

Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice.

Skin lesions, cataracts, and congenital anomalies have been frequently associated with inherited deficiencies in enzymes that synthesize cholesterol. Lanosterol synthase (LSS) converts (S)-2,3-epoxysqualene to lanosterol in the cholesterol biosynthesis pathway. Biallelic mutations in LSS have been reported in families with congenital cataracts and, very recently, have been reported in cases of hypotrichosis. However, it remains to be clarified whether these phenotypes are caused by LSS enzymatic deficiencies in each tissue, and disruption of LSS enzymatic activity in vivo has not yet been validated. We identified two patients with novel biallelic LSS mutations who exhibited congenital hypotrichosis and midline anomalies but did not have cataracts. We showed that the blockade of the LSS enzyme reaction occurred in the patients by measuring the (S)-2,3-epoxysqualene/lanosterol ratio in the forehead sebum, which would be a good biomarker for the diagnosis of LSS deficiency. Epidermis-specific Lss knockout mice showed neonatal lethality due to dehydration, indicating that LSS could be involved in skin barrier integrity. Tamoxifen-induced knockout of Lss in the epidermis caused hypotrichosis in adult mice. Lens-specific Lss knockout mice had cataracts. These results confirmed that LSS deficiency causes hypotrichosis and cataracts due to loss-of-function mutations in LSS in each tissue. These mouse models will lead to the elucidation of the pathophysiological mechanisms associated with disrupted LSS and to the development of therapeutic treatments for LSS deficiency.

Nutritional Strategies to Prevent Lens Cataract: Current Status and Future Strategies.

Oxidative stress and the subsequent oxidative damage to lens proteins is a known causative factor in the initiation and progression of cataract formation, the leading cause of blindness in the world today. Due to the role of oxidative damage in the etiology of cataract, antioxidants have been prompted as therapeutic options to delay and/or prevent disease progression. However, many exogenous antioxidant interventions have to date produced mixed results as anti-cataract therapies. The aim of this review is to critically evaluate the efficacy of a sample of dietary and topical antioxidant interventions in the light of our current understanding of lens structure and function. Situated in the eye behind the blood-eye barrier, the lens receives it nutrients and antioxidants from the aqueous and vitreous humors. Furthermore, being a relatively large avascular tissue the lens cannot rely of passive diffusion alone to deliver nutrients and antioxidants to the distinctly different metabolic regions of the lens. We instead propose that the lens utilizes a unique internal microcirculation system to actively deliver antioxidants to these different regions, and that selecting antioxidants that can utilize this system is the key to developing novel nutritional therapies to delay the onset and progression of lens cataract.

Neglected Congenital Glaucoma With Lens Coloboma.

PURPOSE: To report a case of lens coloboma in a case of neglected primary congenital glaucoma. MATERIALS AND METHODS: A 5-year-old boy was brought by the parents with complaints of diminution of vision in both eyes noticed for 8 months. There was a history of enlargement of eyes since 1 year of age. RESULTS: Clinical examination revealed bilateral large eyes with limbal stretching and Haab striae and lens coloboma in the right eye. Dilated examination revealed scalloped border of the crystalline lens superotemporally with broken zonules and lens coloboma in inferotemporal quadrant with absent zonules. There was advanced optic nerve head cupping in both eyes. This lens coloboma is likely an acquired condition due to extensive stretching of the lens and zonules secondary to globe enlargement in neglected buphthalmos. CONCLUSION: A neglected case of congenital glaucoma can lead to lens subluxation along with lens coloboma.

Anti-cataract Effect of Resveratrol in High-Glucose-Treated Streptozotocin-Induced Diabetic Rats.

Resveratrol, which is a polyphenol found in grapes, peanuts, and other plants, has health benefits for various chronic diseases. The aim of the present study was to examine the effect of resveratrol on cataract formation in diabetic rats. Male Wistar rats (7-week-old) were treated with streptozotocin, and the streptozotocin-treated animals were administered 5% D-glucose in drinking water to promote the formation of cataracts by inducing severe hyperglycemia. Resveratrol supplementation (10 or 30 mg/kg/d) in drinking water was initiated immediately after induction of diabetes was confirmed. The full lens images of the horizontal plane were captured with the digital camera system which we developed. Cataract formation was assessed by an observer-based scoring method and by quantitative analysis of digital images of the lens. Cataracts at the peripheral region of the lens were detected 2 weeks after induction of hyperglycemia and progressed depending on the length of the diabetic period. The majority of them developed severe cataracts after 9 weeks of hyperglycemia. Resveratrol did not prevent the appearance of diabetic cataracts but significantly delayed the progression of cataracts compared with controls. The contents of sorbitol and protein carbonyls in lenses of diabetic rats were higher than those of control rats. Resveratrol suppressed the increase in protein carbonyls, but not of sorbitol, in diabetic lenses. These results suggest that resveratrol delays the progression of diabetic cataracts partially through attenuation of oxidative damage to lens proteins. Resveratrol may be beneficial in preventing the progression of diabetic cataracts.

Fatty acids modulate the efficacy of lutein in cataract prevention: Assessment of oxidative and inflammatory parameters in rats.

BACKGROUND: Effects of lutein (L) and fatty acids [linoleic acid (LA), eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) and oleic acid (OA)] on oxidative stress and inflammation in cataract were assessed. METHODS: Cataract was induced in male Wistar rat pups (11 days old) by giving a single dose of sodium selenite (25 µM/kg body weight) by IP. Lutein (1.3 µmol/kg body weight) was given one day before and five days after selenite injection as a micelle with 7.5 mM LA, or 7.5 mM EPA + DHA or 7.5 mM OA. Serum and lens oxidative stress and inflammatory parameters having a bearing cataract were assessed. RESULTS: Serum and lens nitric oxide, MDA and protein carbonyls were significantly (p < 0.05) increased in cataract compared to control and experimental groups. Catalase, SOD, glutathione peroxidase and glutathione transferase activity and glutathione level in serum and lens of cataract group were significantly (p < 0.05) decreased. Serum eicosanoids (PGE2, LTB4, and LTC4) and cytokines (CRP, TNF-α, IL1-ß, and MCP-1) were significantly (p < 0.05) increased in cataract. The activity of cPLA2 and Cox-2 in cataract lens was higher (p < 0.05) compared to other groups. EP-1, NOS-2 and NF-kB expression were higher (p < 0.05) in cataract. The ratio of water insoluble to water soluble protein was increased in cataract lens. Group administered with L + EPA + DHA exhibited highest cataract prevention compared to L + LA and L + OA. Pups given lutein with EPA + DHA had the highest amount of lutein in the lens. CONCLUSIONS: The anti-cataract activity of lutein was influenced by fatty acids and found to be highest with EPA + DHA compared to LA or OA.

Antidiabetic cataract effects of GbE, rutin and quercetin are mediated by the inhibition of oxidative stress and polyol pathway.

One of the earliest critical secondary complications of diabetes is the opacification of the eye lens - a condition strictly associated with diabetic cataract. The study presented here was designed to investigate the effect of Ginkgo biloba extract (GbE), rutin and quercetin on streptozotocin (STZ) induced diabetic cataract (DC) rats. Ten weeks after administration of GbE, rutin and quercetin, the opacity of diabetic rats' lenses was graded under a slit lamp. Then, the levels of malondialdehyde (MDA), reduced glutathione (GSH), advanced glycosylation end products (AGEs), and the activities of aldose reductase (AR) were estimated. The DC-induced rats produced less GSH, higher levels of MDA and AGEs as well as elevated AR activity when compared to the normal group. Administration of GbE, rutin and quercetin remarkably inhibited the AR activity, stimulated the production of glutathione, and decreased the levels of MDA and AGEs in the lenses of DC-induced rats, which eventually delayed the progression of lens opacification in diabetic rats to various degrees. Our results revealed that quercetin had the highest significant (P<0.05) potential to delay the progression of STZ-induced diabetic cataract when compared with rutin and GbE. The mechanism dictating this interesting prowess of quercetin might be attributed to its AR inhibitory strength, anti-lipid peroxidation potential and anti-AGEs activity.

Diosgenin, a Novel Aldose Reductase Inhibitor, Attenuates the Galactosemic Cataract in Rats.

OBJECTIVE: To seek efficient aldose reductase inhibitors (ARIs) with excellent in vitro and in vivo biological activities against rat galactosemic cataract. METHODS: The method was firstly optimized to screen strong ARIs from nonoriented synthetic compounds and natural extracts. Then, diosgenin was assessed on osmotic expansion of primarily cultured lens epithelial cells (LECs) induced by galactose (50 mM). Diosgenin was administered to galactosemic rats by oral (100 and 200 mg/kg) or direct drinking (0.1%) to evaluate its anticataract effects. RESULTS: Diosgenin was found as the strongest ARI with IC50 of 4.59 × 10-6 mol/L. Diosgenin (10 µM) evidently inhibited the formation of tiny vacuoles and upregulation of AR mRNA in LECs. In vivo, diosgenin delayed lens opacification, inhibited the increase of ratio of lens weight to body weight, and decreased AR activity, galactitol level, and AR mRNA expression, especially in the diosgenin drinking (0.1%) group. CONCLUSIONS: Diosgenin was an efficient ARI, which not only significantly decreased the LECs' osmotic expansion in vitro but also markedly delayed progression of rat galactosemic cataract in vivo. Thus, diosgenin rich food can be recommended to diabetic subjects as dietary management to postpone the occurrence of sugar cataract, and diosgenin deserves further investigation for chronic diabetic complications.

Anticataractogenesis and Antiretinopathy Effects of the Novel Protective Agent Containing the Combined Extract of Mango and Vietnamese Coriander in STZ-Diabetic Rats.

The novel protectant against diabetic cataract and diabetic retinopathy is currently required due to the increased prevalence and therapeutic limitation. Based on the advantage of polyphenol on diabetic eye complications, we hypothesized that the combined extract of mango seed Vietnamese coriander (MPO), a polyphenol-rich substance, should possess anticataractogenesis and antiretinopathy in streptozotocin- (STZ-) diabetic rats. MPO at doses of 2, 10, and 50 mg/kg·BW were orally given to STZ-diabetic rats for 10 weeks. Lens opacity was evaluated every week throughout a study period whereas the evaluation of cataract severity and histological changes of both rat lens epithelium and retina together with the biochemical assays of oxidative stress status, aldose reductase, p38MAPK, ERK1/2, and VEGF were performed at the end of experiment. Our data showed that MPO improved cataract and retinopathy in STZ-diabetic rats. The improved oxidative stress status and the decreased p38MAPK, ERK1/2, and VEGF were also observed. Therefore, anticataractogenesis and antiretinopathy of MPO might occur partly via the decreased oxidative stress status and the suppression of aldose reductase, p38MAPK, ERK1/2, and VEGF. This study points out that MPO is the potential candidate protectant against diabetic cataract and diabetic retinopathy. However, the exploration for possible active ingredient (S) still requires further researches.

Pinus densiflora bark extract prevents selenite-induced cataract formation in the lens of Sprague Dawley rat pups.

PURPOSE: Rat pups treated with sodium selenite are typically used as an in vivo model to mimic age-related nuclear cataract. Reactive oxygen species (ROS) production, lipid peroxidation, reduction of antioxidant enzymes, crystalline proteolysis, and apoptosis are considered factors that contribute to pathogenesis of age-related nuclear cataract. In the present study, we investigated whether Pinus densiflora bark extract has potential to prevent cataract formation and elucidated the underlying mechanism. METHODS: Sprague Dawley rats were divided into six groups (n=10). Group 1 rat pups (the control) were treated with only normal saline. The rat pups in groups 2 to 6 were given a subcutaneous injection with sodium selenite (18 µmol/kg bodyweight) on postnatal (P) day 10. Group 3 rat pups (the positive control) were given gastric intubation with curcumin (80 mg/kg bodyweight) on P9, P10, and P11. The rat pups in groups 4 to 6 were given gastric intubation with P. densiflora bark extract 40 mg/kg, 80 mg/kg, and 120 mg/kg, respectively, on P9, P10, and P11. RESULTS: This study showed that P. densiflora bark extract dose-dependently prevented cataract formation. Water-soluble protein, glutathione, superoxide dismutase, glutathione peroxidase, and catalase activity levels were found to be high, and conversely, water-insoluble protein, malondialdehyde, and Ca2+-ATPase were found to be low in the groups treated with P. densiflora bark extract compared to group 2. Real-time PCR analysis showed αA-crystalline, lens-specific m-calpain (Lp84), lens-specific intermediates (filensin and phakinin), and antiapoptotic factor (Bcl-2) were downregulated, and the apoptotic factors (caspase-3 and Bax) and plasma membrane Ca2+-ATPase (PMCA-1) were upregulated in group 2 compared to group 1. P. densiflora bark extract regulated the imbalance of these genes. The increased cleavage form of caspase-3 was lowered in the groups treated with P. densiflora bark extract. In conclusion, P. densiflora bark extract prevented selenite-induced cataract formation via regulating antioxidant enzymes, inhibiting m-calpain-induced proteolysis, and apoptosis, and thus, maintained the transparency of the lens. CONCLUSIONS: These results suggested that P. densiflora bark extract could be a new agent for preventing age-related nuclear cataract.

Macular pigment density variation after supplementation of lutein and zeaxanthin using the Visucam® 200 pigment module: Impact of age-related macular degeneration and lens status.

PURPOSE: To assess the evolution of macular pigment optical density (MPOD) following supplementation with various macular formulations obtained with the Visucam® 200, and to study the factors affecting MPOD measurements. MATERIALS AND METHODS: In this prospective, randomized, double-masked multicenter study, patients were divided into 2 groups: group A (patients without retinal pathology who underwent cataract surgery 1 month previously) and group B (patients with neovascular age-related macular degeneration [AMD] in one eye). In each group, half of the patients were randomly assigned to receive a food supplementation either with or without carotenoids (5mg of Lutein and 1mg of Zeaxanthin). Outcome measures included MPOD responses obtained with the Visucam® 200 for one year. RESULTS: In total, 126 subjects (52 men, 74 women) with a mean age of 75.3±7.61 years were enrolled. Mean MPOD values at the time of inclusion were statistically lower in group A (0.088 density unit [DU]) compared to group B (0.163 DU, P<0.05). No statistically significant increase in MPOD was noted in either group, even after discontinuation of the supplementation. By multiple regression analysis, age, female gender, lens status and the presence of AMD seemed to significantly affect MPOD measurements. CONCLUSION: No significant improvement in MPOD seems to be detected with the Visucam® 200 after carotenoid supplementation. The MPOD measurement seems to be highly affected by cataract extraction and the presence of AMD.

Anti-Cataract Potential of Heliotropium indicum Linn on Galactose-Induced Cataract in Sprague-Dawley Rats.

OBJECTIVE: To evaluate the anti-cataract potential of an aqueous whole plant extract of Heliotropium indicum (HIE) on galactose-induced cataract in Sprague-Dawley rats. MATERIALS AND METHODS: Cataract scores were recorded in 3-week-old Sprague-Dawley rats in which cataract was being induced by an oral administration of 1500 mgkg-1 galactose twice daily for 4 weeks, and concurrently being treated with 30, 100, or 300 mgkg-1 HIE daily over the induction period. Fasting blood glucose was monitored at weekly intervals. Changes in body weight as well as total lens protein, lens glutathione, and superoxide dismutase (SOD) were determined initially, and at the end of the experimental period. Crystalline lens weight-to-body-weight ratio was also determined for the various treatment groups at the end of the experimental period. Preliminary phytochemical screening, total antioxidant capacity, and reducing power assays were conducted on HIE. RESULTS: The 30 and 100 mgkg-1 HIE-treated rats recorded significantly lower (p ≤ 0.05-0.001) cataract scores (indicating very significant delays in cataractogenesis by the 3rd and 4th weeks of treatment) and blood glucose levels. Rats with delayed cataractogenesis also exhibited significant (p ≤ 0.05-0.001) weight gain, and reduction in lens weight. Total lens proteins glutathione and SOD levels in the crystalline lens were also significantly preserved (p ≤ 0.01-0.001). HIE showed substantial antioxidant capacity and reducing power. CONCLUSION: The aqueous whole plant extract of Heliotropium indicum delays cataractogenesis at an optimum dose of 30 mgkg-1 in Sprague-Dawley rats.

Selenite and ebselen supplementation attenuates D-galactose-induced oxidative stress and increases expression of SELR and SEP15 in rat lens.

Selenite and ebselen supplementation has been shown to possess anti-cataract potential in some experimental animal models of cataract, however, the underlying mechanisms remain unclear. The present study was designed to evaluate the anti-cataract effects and the underlying mechanisms of selenite and ebselen supplementation on galactose induced cataract in rats, a common animal model of sugar cataract. Transmission electron microscopy images of lens fiber cells (LFC) and lens epithelial cells (LEC) were observed in D-galactose-induced experimental cataractous rats treated with or without selenite and ebselen, also redox homeostasis and expression of proteins such as selenoprotein R (SELR), 15kD selenoprotein (SEP15), superoxide dismutase 1 (SOD1), catalase (CAT), ß-crystallin protein, aldose reductase (AR) and glucose-regulated protein 78 (GRP78) were estimated in the lenses. The results showed that D-galactose injection injured rat lens and resulted in cataract formation; however, selenite and ebselen supplementation markedly alleviated ultrastructural injury of LFC and LEC. Moreover, selenite and ebselen supplementation could mitigate the oxidative damage in rat lens and increase the protein expressions of SELR, SEP15, SOD1, CAT and ß-crystallin, as well as decrease the protein expressions of AR and GRP78. Taken together, these findings for the first time reveal the anti-cataract potential of selenite and ebselen in galactosemic cataract, and provide important new insights into the anti-cataract mechanisms of selenite and ebselen in sugar cataract.

Magnesium taurate prevents cataractogenesis via restoration of lenticular oxidative damage and ATPase function in cadmium chloride-induced hypertensive experimental animals.

Previously we found that hypertension potentiates the risk the cataractogenesis. In the present study, we investigated the protective effects of magnesium taurate (MgT) on hypertension and associated lenticular damages against cadmium chloride (CdCl2)-induced hypertensive animals. Male Sprague-Dawley albino rats (150-180g) were assigned to five experimental groups (n=6). Among the five groups, normal group received 0.3% carboxymethyl cellulose (10ml/kg/day, p.o.). Hypertension control group received CdCl2 (0.5mg/kg/day, i.p.). Tests and standard groups received MgT (3 and 6mg/kg/day, p.o.) and amlodipine (3mg/kg/day, p.o.) concurrently with CdCl2 respectively, for six consecutive weeks. Blood pressure, heart rate, and eyes were examined biweekly, and pathophysiological parameters in serum and eye lenses were evaluated after six weeks of the experimental protocol. The chronic administration of MgT concurrently with CdCl2 significantly restored the blood pressure, serum and lens antioxidants (CAT, SOD, GPx, and GSH), MDA level, and ions (Na+, K+, and Ca2+). Additionally, MgT treatment led to significant increase in the lens proteins (total and soluble), Ca2+ ATPase, and Na+K+ ATPase activity as compared to hypertension control group. Ophthalmoscope observations indicated that MgT treatments delayed the progression of cataract against the hypertensive state. The study shows that MgT prevents the progression of cataractogenesis via restoration of blood pressure, lenticular oxidative damages, and lens ATPase functions in the hypertensive state. The results suggest that MgT supplement may play a beneficial role to manage hypertension and associated cataractogenesis.

Protective effect of Tephrosia purpurea in diabetic cataract through aldose reductase inhibitory activity.

PURPOSE: Tephrosia purpurea (T. purpurea) has been reported to prevent cataract formation in senile cataract model as well as proven effective in STZ induced type 1 diabetes. Aldose reductase (AR) is a key enzyme in the intracellular polyol pathway responsible for the development of diabetic cataract. OBJECTIVE: To investigate the effects of T. purpurea in the light of inhibition of aldose reductase enzyme in polyol pathway. METHODS: We studied the effects of alcoholic extract and flavonoid fraction of T. purpurea in streptozotocin (STZ, 45mg/kg, i.v.)-induced type I diabetic cataract in rats. The animals were divided into five groups as control, control treated with alcoholic and flavonoid fraction, diabetic control and diabetic treated with alcoholic and flavonoid fraction. In-vitro aldose reductase inhibitory activity was also evaluated. Further, molecular docking study was performed with crystal structure of aldose reductase and its known chemical constituents of the plant. RESULTS: The IC50 value of alcoholic extract for aldose reductase inhibition was found to be 209.13µg/ml, and that of flavonoid fraction was found to be 46.73µg/ml. Administration of STZ produced significantly abnormal levels of serum glucose, serum insulin, soluble protein and antioxidants in the lens homogenate. Treatment with alcoholic extract and flavonoid fraction of T. purpurea were able to normalize these levels. Some of the active constituents of T. purpurea showed significant interactions with aldose reductase enzyme in molecular docking studies. CONCLUSIONS: Our data suggested that both the extracts might be helpful in delaying the development of diabetic cataract due to the presence of rutin and quercetin. This beneficial effect may be due to its significant inhibition of aldose reductase enzyme and anti-oxidant activity.