Age-related Nuclear Cataract Research Articles

Aqueous humor perturbations in chronic smokers: a proteomic study

The detrimental effects of smoking are multisystemic and its effects on the eye health are significant. Smoking is a strong risk factor for age-related nuclear cataract, age-related macular degeneration, glaucoma, delayed corneal epithelial healing and increased risk of cystoid macular edema in patients with intermediate uveitis among others. We aimed to characterize the aqueous humor (AH) proteome in chronic smokers to gain insight into its perturbations and to identify potential biomarkers for smoking-associated ocular pathologies. Compared to the control group, chronic smokers displayed 67 (37 upregulated, 30 downregulated) differentially expressed proteins (DEPs). Analysis of DEPs from the biological point of view revealed that they were proteins involved in complement activation, lymphocyte mediated immunity, innate immune response, cellular oxidant detoxification, bicarbonate transport and platelet degranulation. From the molecular function point of view, DEPs were involved in oxygen binding, oxygen carrier activity, hemoglobin binding, peptidase/endopeptidase/cysteine-type endopeptidase inhibitory activity. Several of the upregulated proteins were acute phase reactant proteins such as clusterin, alpha-2-HS-glycoprotein, fibrinogen, alpha-1-antitrypsin, C4b-binding protein and serum amyloid A-2. Further research should confirm if these proteins might serve as biomarkers or therapeutic target for smoking-associated ocular diseases.

HO-1-Mediated Autophagic Restoration Protects Lens Epithelial Cells Against Oxidative Stress and Cellular Senescence.

Oxidative stress and cellular senescence are risk factors for age-related cataract. Heme oxygenase 1 (HO-1) is a critical antioxidant enzyme and related to autophagy. Here, we investigate the crosstalk among HO-1, oxidative stress, and cellular senescence in mouse lens epithelial cells (LECs). The gene expression of HO-1, p21, LC3, and p62 was measured in human samples. The protective properties of HO-1 were examined in hydrogen peroxide (H2O2)-damaged LECs. Autophagic flux was examined by Western blot and mRFP-GFP-LC3 assay. Western blotting and lysotracker staining were used to analyze lysosomal function. Flow cytometry was used to detect intracellular reactive oxygen species and analyze cell cycle. Senescence-associated β-galactosidase assay was used to determine cellular senescence. The crosstalk between HO-1 and transcription factor EB (TFEB) was further observed in TFEB-knockdown cells. The TFEB binding site in the promoter region of Hmox1 was predicted by the Jasper website and was confirmed by chromatin immunoprecipitation assay. HO-1 gene expression decreased in LECs of patients with age-related nuclear cataract, whereas mRNA expression levels of p21, LC3, and p62 increased. Upon H2O2-induced oxidative stress, LECs showed the characteristics of autophagic flux blockade, lysosomal dysfunction, and premature senescence. Interestingly, HO-1 significantly restored the impaired autophagic flux and lysosomal function and delayed cellular senescence. TFEB gene silencing greatly reduced the HO-1-mediated autophagic restoration, leading to a failure to prevent LECs from oxidative stress and premature senescence. We demonstrated HO-1 effects on restoring autophagic flux and delaying cellular senescence under oxidative stress in LECs, which are dependent on TFEB.

Dehydroalanine and dehydrobutyrine in aging and cataractous lenses reveal site-specific consequences of spontaneous protein degradation.

Protein post-translational modifications (PTMs) have been associated with aging and age-related diseases. PTMs are particularly impactful in long-lived proteins, such as those found in the ocular lens, because they accumulate with age. Two PTMs that lead to protein-protein crosslinks in aged and cataractous lenses are dehydroalanine (DHA) and dehydrobutyrine (DHB); formed from cysteine/serine and threonine residues, respectively. The purpose of this study was to quantitate DHA and DHB in human lens proteins as a function of age and cataract status. Human lenses of various ages were divided into five donor groups: transparent lenses (18-22-year-old, 48-64-year-old, and 70-93-year-old) and cataractous human lenses of two age groups (48-64-year-old lenses, and 70-93-year-old lenses) and were subjected to proteomic analysis. Relative DHA and DHB peptide levels were quantified and compared to their non-modified peptide counterparts. For most lens proteins containing DHA or DHB, higher amounts of DHA- and DHB-modified peptides were detected in aged and cataractous lenses. DHA-containing peptides were classified into three groups based on abundance changes with age and cataract: those that (1) increased only in age-related nuclear cataract (ARNC), (2) increased in aged and cataractous lenses, and (3) decreased in aged lenses and ARNC. There was no indication that DHA or DHB levels were dependent on lens region. In most donor groups, proteins with DHA and DHB were more likely to be found among urea-insoluble proteins rather than among water- or urea-soluble proteins. DHA and DHB formation may induce structural effects that make proteins less soluble in water that leads to age-related protein insolubility and possibly aggregation and light scattering.

Proteome Remodeling of the Eye Lens at 50 Years Identified With Data-Independent Acquisition

The eye lens is responsible for focusing and transmitting light to the retina. The lens does this in the absence of organelles, yet maintains transparency for at least 5 decades before onset of age-related nuclear cataract (ARNC). It is hypothesized that oxidative stress contributes significantly to ARNC formation. It is in addition hypothesized that transparency is maintained by a microcirculation system that delivers antioxidants to the lens nucleus and exports small molecule waste. Common data-dependent acquisition methods are hindered by dynamic range of lens protein expression and provide limited context to age-related changes in the lens. In this study, we utilized data-independent acquisition mass spectrometry to analyze the urea-insoluble membrane protein fractions of 16 human lenses subdivided into three spatially distinct lens regions to characterize age-related changes, particularly concerning the lens microcirculation system and oxidative stress response. In this pilot cohort, we measured 4788 distinct protein groups, 46,681 peptides, and 7592 deamidated sequences, more than in any previous human lens data-dependent acquisition approach. Principally, we demonstrate that a significant proteome remodeling event occurs at approximately 50 years of age, resulting in metabolic preference for anaerobic glycolysis established with organelle degradation, decreased abundance of protein networks involved in calcium-dependent cell–cell contacts while retaining networks related to oxidative stress response. Furthermore, we identified multiple antioxidant transporter proteins not previously detected in the human lens and describe their spatiotemporal and age-related abundance changes. Finally, we demonstrate that aquaporin-5, among other proteins, is modified with age by post-translational modifications including deamidation and truncation. We suggest that the continued accumulation of each of these age-related outcomes in proteome remodeling contribute to decreased fiber cell permeability and result in ARNC formation.

Biliverdin/Bilirubin Redox Pair Protects Lens Epithelial Cells against Oxidative Stress in Age-Related Cataract by Regulating NF-κB/iNOS and Nrf2/HO-1 Pathways.

Age-related cataract (ARC) is the leading cause of vision impairment globally. It has been widely accepted that excessive reactive oxygen species (ROS) accumulation in lens epithelial cells (LECs) is a critical risk factor for ARC formation. Biliverdin (BV)/bilirubin (BR) redox pair is the active by-product of heme degradation with robust antioxidative stress and antiapoptotic effects. Thus, we purpose that BV and BR may have a therapeutic effect on ARC. In the present study, we determine the expression levels of enzymes regulating BV and BR generation in human lens anterior capsule samples. The therapeutic effect of BV/BR redox pair on ARC was assessed in hydrogen peroxide (H2O2)-damaged mouse LECs in vitro. The NF-κB/inducible nitric oxide synthase (iNOS) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathways were evaluated to illustrate the molecular mechanism. The results revealed that the mRNA expressions of Nrf2, HO-1, and biliverdin reductase A (BVRA) were all decreased in human samples of age-related nuclear cataract. BV/BR redox pair pretreatment protected LECs against H2O2 damage by prohibiting NF-κB p65 nuclear trafficking, ameliorating iNOS expression, reducing intracellular and mitochondrial ROS levels, and restoring glutathione (GSH) and superoxide dismutase (SOD) levels. BV and BR pretreatment also regulated the expression of apoptotic molecules (Bax, Bcl-2, and cleaved caspase-3), thus decreasing the apoptosis of LECs. In addition, BV/BR pair promoted Nrf2 nuclear accumulation and HO-1 induction, whereas the knockdown of BVRA counteracted the effect of BV on activating Nrf2/HO-1 pathway and antiapoptosis. These findings implicated that BV/BR redox pair protects LECs against H2O2-induced apoptosis by regulating NF-κB/iNOS and Nrf2/HO-1 pathways. Moreover, BVRA is responsible for BV-mediated cytoprotection by reductive conversion of BV to BR. This trial is registered with ChiCTR2000036059

MiR-34a-5p Negatively Regulates Oxidative Stress on Lens Epithelial Cells by Silencing GPX3 – A Novel Target

PurposeMiR-34a-5p is reported to be related with age-related nuclear cataract. This study investigated the mechanism of miR-34a-5p in the regulation of oxidative stress on lens epithelial cells.MethodsThe three candidate miRNAs were screened by CCK-8 assays after transfection of mimics or inhibitor in H2O2-treated HLE-B3 cells. The apoptosis, ROS level and GPX activity of HLE-B3 cells transfected with miR-34a-5p mimics or inhibitor were analysed by flow cytometry, cellular ROS and GPX activity test. The target genes of miR-34a-5p were predicted by proteomic and bioinformatic analysis. The relationship between miR-34a-5p and GPX3 were internally validated by qRT-PCR and Western blot and externally verified by dual-luciferase reporter assay. The effect of miR-34a-5p-GPX3 axis on regulation of oxidative stress in HLE-B3 cells were conducted by overexpression of GPX3 and tested by flow cytometry analysis, cellular ROS and GPX detection.ResultsThe viability of H2O2-treated HLE-B3 cells were weakened by up-regulated miR-34a-5p. Cell apoptosis and oxidative damage were also induced by overexpression of miR-34a-5p. GPX3 and SRC were identified as target genes of miR-34a-5p by combined analysis of proteomic and bioinformatics, while GPX3 was selected for further research for its connection with anti-oxidation. Western blot and qRT-PCR tests proved that GPX3 is negatively regulated by miR-34a-5p. Dual-luciferase reporter assay verified that GPX3 is the direct target of miR-34a-5p. The increased oxidative stress induced by transfection of miR-34a-5p mimics in H2O2-treated HLE-B3 cells was attenuated by overexpression of GPX3.ConclusionsMiR-34a-5p is a negative regulator of oxidative stress on lens epithelial cells and the mechanism is by silencing the expression of GPX3. These data suggest that miR-34a-5p may be a potential novel therapeutic target for the prevention and treatment of age-related cataract.

Investigation of Novel Nanoplatforms for Delivery of an Anticataract Drug in Whole Lens Cultures

Cataracts are a leading cause of blindness, but the only available treatment is surgery, which may not be a viable option for many patients. Instead, pharmacological interventions that target cataractogenesis at the molecular level represent an attractive method for preventing or delaying cataract formation. Antioxidant drugs like N-(2-mercaptopropionyl)glycine may interfere with oxidative processes that lead to age-related nuclear cataracts. Nevertheless, achieving therapeutic concentrations in the lens has proven challenging. Novel delivery strategies such as functionalized nanodiamonds offer several advantages over conventional platforms in terms of stability and customizability. Therefore, we investigated the effects of three different types of functionalized nanodiamonds on the uptake and efficacy of a potential anticataract agent in a whole organ culture model of oxidative insult in the lens. Lenses treated with sodium selenite exhibited detrimental morphological changes and significantly deteriorated redox status. Lenses treated with the neat drug showed marked improvements. However, only hydroxylated nanodiamonds appeared to improve drug uptake, and their effects on lens glutathione and cysteine were modest. This work represents a critical step in understanding the anticataract effects of N-(2-mercaptopropionyl)glycine, and it suggests that other drug delivery strategies may be warranted to realize these effects in vivo.

Non-Modifiable Risk Factors for Cataract Genesis

The review reflects the current data on unmodified risk factors for cataract development; most prominent are genetic factors and age. Research shows that about half of nuclear and two-thirds of cortical cataracts can be hereditary. Congenital cataracts are hereditary in 25 % of cases, of which 75 % are autosomal dominant. From 30 % to 50 % of congenital cataracts are caused by mutations in genes encoding proteins in the structure of the lens. To date, 115 genes have been identified associated with syndromic and non-syndromic cataracts. Proof of the genetic theory is the development of nuclear cataract in Stickler syndrome (SS), a relatively rare multisystem connective tissue disease inherited in an autosomal dominant manner. The syndrome is characterized by structural abnormalities in collagens of types 2, 9 and 11 and manifests itself in various clinical signs, including the development of facial skeleton anomalies, damage to the vision organ, the musculoskeletal system and the auditory system. Ophthalmic complications of SS are represented by a combination of pathological myopia, retinal detachment, ocular hypertension, early vitreous liquefaction and premature cataract development. Age is the main unmodified risk factor for developing cataracts. The most common form of cataract is age-related nuclear cataract, which in developing countries accounts for 50 % to 90 % of the total number of cases (> 70 versus ≤ 65 years, OR = 12.7). The pathogenesis of age-related nuclear cataract is associated with oxidative damage to proteins under certain conditions: a decrease in the concentration of glutathione (GSH) and vitamin C in the lens nucleus. When examining the frequency of cortical cataract, there was also a relationship with an increase in the age of patients (> 70 years versus ≤ 65 years, OR = 5.96). With age, a barrier is created for the advancement of GSH from the site of its synthesis and regeneration in the cortical layer of the lens towards the nucleus. Numerous experimental and morphological studies confirm the accommodative theory of the development of age-related cortical cataract. Lens deformations caused by accommodation forces lead to heterogeneity of the lens density at the border of the nucleus and cortical layers, an increase in light scattering and damage to the lens fibers. Genetic predisposition and age are interactions of many complex factors that can contribute to the development of cataracts.

Comparison of the IOLMaster 700 and the Pentacam in the Analysis of the Lens Nuclear Density Before the Cataract Surgery.

Purpose: To evaluate the difference of the lens nuclear density measured before and after mydriasis by using the IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany) and the Pentacam Scheimpflug imaging (Pentacam HR, Oculus Incorporation, Wetzlar, Germany) and investigate the relationship between the measurement data and the phacoemulsification parameters.Methods: Patients with age-related nuclear cataracts diagnosed on the slit-lamp examination were enrolled in the age range of 53–76 years. No patient had a history of ocular surgery, laser treatment, or general disorders affecting vision. The mean optical density (OD) was measured by the IOLMaster 700 by using the Image-Pro® Plus software before and after mydriasis. The Pentacam nucleus densitometry (PND) was obtained automatically from the Pentacam Scheimpflug imaging and compared with OD. The correlation between OD and effective phacoemulsification time (EPT), PND, and EPT were analyzed, respectively.Results: In this study, 53 eyes of 52 patients were evaluated. Before and after mydriasis, the mean OD values were 64.34 ± 23.31 and 63.81 ± 23.21 pixel units, respectively; the mean PND values were 28.51 ± 11.42 and 25.41 ± 11.31, respectively; and the mean EPT value was 6.24 ± 3.49. The Bland–Altman analysis showed that the lens nuclear densities of the two devices were highly consistent. There was no significant difference in the OD values (t = 0.455, p > 0.05) before and after mydriasis, but the difference has existed in the PND values (t = 2.509, p < 0.05). The OD and PND values were positively correlated with EPT before and after mydriasis (rOD−Before = 0.604, rOD−After = 0.593, rPND−Before = 0.701, and rPND−After = 0.891, p < 0.01).Conclusion: The combination of the IOLMaster 700 and the Image-Pro® Plus software can quantitatively evaluate the degree of the cataract lens opacification. It has good consistency with the Pentacam and is positively correlated with the phacoemulsification parameters. It is expected to become a new method to predict the phacoemulsification parameters before and during cataract surgery.

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.

Relationship of Objective Metrics for Quantifying Age-related Nuclear Cataracts with Visual Acuity and Phacodynamics

IntroductIon: An appropriate evaluation cataract degree is essential for deciding to proceed with surgery. Our purpose was to study the relationship between objective metrics for quantifying age-related nuclear cataracts with visual impairment and phacodynamics parameters. Methods: Thirty eyes (30 patients) with age-related nuclear cataract were submitted to phacoemulsification. The average lens density (0 to 100) was evaluated by using a rotating Scheimpflug system (Pentacam HR, Oculus, Wetzlar, Germany) and the nuclear opalescence (NO) score was subjectively assessed using the Lens Opacities Classification System III (LOCS III). This different parameters were correlated with preoperative corrected distance visual acuity (CDVA) and cumulative dissipated energy (CDE). Results: The preoperative CDVA was correlated with the Scheimpflug-measured lens nuclear density value (r=0.617, p<0.01). The CDE was posi-tively correlated with the Scheimpflug-derived average density variable (r=0.681 p<0.01) than with LOCS III NO (r=0.661, p<0.01). Conclusion: The Scheimpflug-measured average density was correlated with subjective lens grading and preoperative CDVA. This metric also presented the highest positive correlation with phacodynamics.

Quantitative X-ray tomographic analysis reveals calcium precipitation in cataractogenesis

Cataracts, named for pathological light scattering in the lens, are known to be associated with increased large protein aggregates, disrupted protein phase separation, and/or osmotic imbalances in lens cells. We have applied synchrotron phase contrast X-ray micro-computed tomography to directly examine an age-related nuclear cataract model in Cx46 knockout (Cx46KO) mice. High-resolution 3D X-ray tomographic images reveal amorphous spots and strip-like dense matter precipitates in lens cores of all examined Cx46KO mice at different ages. The precipitates are predominantly accumulated in the anterior suture regions of lens cores, and they become longer and dense as mice age. Alizarin red staining data confirms the presence of calcium precipitates in lens cores of all Cx46KO mice. This study indicates that the spatial and temporal calcium precipitation is an age-related event associated with age-related nuclear cataract formation in Cx46KO mice, and further suggests that the loss of Cx46 promotes calcium precipitates in the lens core, which is a new mechanism that likely contributes to the pathological light scattering in this age-related cataract model.

Association of optical cataract indices with cataract severity and visual function.

The purpose of this study is to determine the correlation between subjective and optical measurements used during cataract evaluation, including the iTrace Dysfunctional Lens Index (DLI), the HD Analyzer Objective Scatter Index (OSI), Lens Opacities Classification System III (LOCS III), Visual Function-14 Questionnaire (VF-14), and the Pelli-Robson Contrast Sensitivity Chart (PRCSC). Seventy eyes from 70 patients were enrolled, including all stages of age-related nuclear cataracts. The LOCS III-NO with a cutoff of 3.2 was chosen to divide the population into two groups. Eyes with corneal or retinal pathology were excluded. All patients were evaluated with the iTrace's DLI, HD Analyzer's OSI, LOCS III, VF-14, and the PRCSC during each follow-up visit. Correlation analyses were performed using Stata software, version 14.0, StataCorp. The LOCS III-NO, DLI, OSI, and VF-14 questionnaire each correlated moderately with the BCVA with a Spearman rho value of 0.37, - 0.45, 0.40, and- 0.35, respectively. The DLI correlated moderately with LOCS III-NO with a rho value of - 0.37 and with the VF-14 questionnaire with a rho value of 0.35. The OSI correlated with both the contrast sensitivity and DLI with a rho value of - 0.35 and - 0.55, respectively. The DLI correlated with cataract symptoms (measured by the VF-14 questionnaire) in addition to BCVA. The OSI correlated moderately with contrast sensitivity and BCVA. The highest correlation was between DLI and OSI.

Acceleration of age-induced proteolysis in the guinea pig lens nucleus by in vivo exposure to hyperbaric oxygen: A mass spectrometry analysis

Hyperbaric oxygen (HBO) treatment of animals or ocular lenses in culture recapitulates many molecular changes observed in human age-related nuclear cataract. The guinea pig HBO model has been one of the best examples of such treatment leading to dose-dependent development of lens nuclear opacities. In this study, complimentary mass spectrometry methods were employed to examine protein truncation after HBO treatment of aged guinea pigs. Quantitative liquid chromatography-mass spectrometry (LC-MS) analysis of the membrane fraction of guinea pig lenses showed statistically significant increases in aquaporin-0 (AQP0) C-terminal truncation, consistent with previous reports of accelerated loss of membrane and cytoskeletal proteins. In addition, imaging mass spectrometry (IMS) analysis spatially mapped the acceleration of age-related αA-crystallin truncation in the lens nucleus. The truncation sites in αA-crystallin closely match those observed in human lenses with age. Taken together, our results suggest that HBO accelerates the normal lens aging process and leads to nuclear cataract.

Taurine supplementation protects lens against glutathione depletion.

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. 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. 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. 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.

Effect of Reformation of the Anterior Chamber by Air or by Ringer’s lactate solution on Corneal Endothelial count and morphology after Phacoemulsification

Background:The corneal endothelium has no ability of regeneration, so any decrease in its density is irreversible and can lead to permanent blurring of vision and pain. Direct contact between air and the corneal endothelium may cause endothelial damage. Aim:To compare the effect of reformation of the anterior chamber after phacoemulsification, using air and ringer’s lactate solution injection, on corneal endothelial count and morphology. Subject and method:A prospective interventional randomized comparative study includes 76 eyes of 76 patients, prepared for phacoemulsification surgery in the period from October 2018 to March 2019. Corneal endothelial morphology and count examined by specular microscopy, and the results recorded for all cases before the surgery. Patients examined by slit lamp biomicroscope and divided randomly into two groups, and both groups were diagnosed with grade 1-2 age related nuclear cataract (according to Lens opacity classification system III). Both groups underwent phacoemulsification surgery with IOL implantation by single well-trained surgeon, group 1 will be subjected to anterior chamber reformation with 0.1 ml air injection while group 2 will be subjected to reformation of the anterior chamber with ringer’s lactate solution. Corneal endothelial morphology and count to be evaluated at 1 week, 1 month and 3 months postoperatively. Results:no significant statistical difference regarding the percentage of CCT changes, cell loss, coefficient of variation and hexagonality between the two groups at baseline and all subsequent visits. Conclusion:no significant difference between air and ringer's lactate solution on the corneal endothelial count and morphology.

Oral consumption of α-glucosyl-hesperidin could prevent lens hardening, which causes presbyopia

Presbyopia is one of the most well-known diseases of the eye, predominantly affecting the adult population after 50 years’. Due to hardening of the lens and failure of accommodative change, patients lose the ability to focus on near objects. This eye symptom is reported to be an early symptom of age-related nuclear cataract, and we have previously reported that hesperetin treatment could delay the onset of nuclear cataractogenesis induced by sodium selenite. In this study, we examined whether oral intake of α-glucosyl-hesperidin (G-Hsd), which has greater water solubility than hesperetin, could delay the onset of presbyopia. G-Hsd treatment protected lens elasticity, upregulated the mRNA expression of anti-oxidative enzymes like glutathione reductase and thioredoxin reductase 1 in the plasma and lens, and prevented premature cataract symptoms in selenite-induced cataract rat lens. Thus, the anti-presbyopic effects of G-Hsd were attributed, at least in part, to its antioxidant effects. G-Hsd represents the first oral treatment agent with anti-presbyopia and/or anti-cataract properties.

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10), LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1 (rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.

Age-dependent changes in glutathione metabolism pathways in the lens: New insights into therapeutic strategies to prevent cataract formation-A review.

Ocular tissues possess a robust antioxidant defence system to minimize oxidative stress and preserve tissue structure and function. Glutathione (GSH) is a powerful antioxidant and in the lens exists at unusually high concentrations. However, with advancing age, GSH levels deplete specifically in the lens centre initiating a chain of biochemical events that ultimately result in protein aggregation, light scattering and age-related nuclear cataract. However, antioxidant supplementation has been shown to be ineffective in preventing or delaying cataract indicating that a better understanding of the delivery, uptake and metabolism of GSH in the different regions of the lens is required. This information is essential for the development of scientifically informed approaches that target the delivery of GSH to the lens nucleus, the region of the lens most affected by age-related cataract.

Molecular Processes Implicated in Human Age-Related Nuclear Cataract.

Human age-related nuclear cataract is commonly characterized by four biochemical features that involve modifications to the structural proteins that constitute the bulk of the lens: coloration, oxidation, insolubility, and covalent cross-linking. Each of these is progressive and increases as the cataract worsens. Significant progress has been made in understanding the origin of the factors that underpin the loss of lens transparency. Of these four hallmarks of cataract, it is protein-protein cross-linking that has been the most intransigent, and it is only recently, with the advent of proteomic methodology, that mechanisms are being elucidated. A diverse range of cross-linking processes involving several amino acids have been uncovered. Although other hypotheses for the etiology of cataract have been advanced, it is likely that spontaneous decomposition of the structural proteins of the lens, which do not turn over, is responsible for the age-related changes to the properties of the lens and, ultimately, for cataract. Cataract may represent the first and best characterized of a number of human age-related diseases where spontaneous protein modification leads to ongoing deterioration and, ultimately, a loss of tissue function.