Cataract Progression Research Articles

Protective effect of apelin-13 in lens epithelial cells via inhibiting oxidative stress-induced apoptosis

BackgroundIt is widely accepted that glaucoma-induced oxidative stress expedites cataracts’ process. Therefore, we examined the effects of apelin-13 against oxidative stress-induced damage in human lens epithelial cells (HLECs) and investigated the potential pathogenic mechanism of acute primary angle-closure glaucoma.MethodsThis experiment included five groups: control, H2O2, apelin-13 + H2O2, ML221 + H2O2, and apelin-13 + ML221 + H2O2. ML221 was employed in rescue experiments as an APJ antagonist. HLECs were pretreated with or without apelin-13 and subsequently exposed to H2O2. HLECs’ viability was assessed by CCK8. Cell apoptosis was determined using Annexin V-FITC/PI staining. The mitochondrial membrane potential was assessed by fluorescent probe JC-1. Intracellular G6PD activity, NADPH/NADP+, and GSH/GSSG ratios were detected to assess the cells’ oxidative damage.ResultApelin-13 reversed the H2O2-induced decrease in cell viability. The increased expression of G6PD and GLTU1, the G6PD, GSH/GSSG and NADPH/NADP + levels showed that apelin-13 can mitigate the H2O2-induced inhibition of the pentose phosphate pathway and dysregulation of cell redox status in the apelin-13 + H2O2 group compared with the H2O2 group. In H2O2-treated HLECs, apelin-13 can mitigate cell apoptosis, promote Bcl-2 expression, and suppress the Bax and Caspase-3 expression. In addition, H2O2 substantially reduced the mitochondrial membrane potential in HLECs, which was reversed by apelin-13. Notably, the inhibition of APJ intensified oxidative damage in H2O2-induced HLECs, demonstrating that the effects of apelin-13 were hindered by ML221.ConclutionsApelin-13 reduced oxidative damage and apoptosis in HLECs through APJ. These results demonstrate that apelin-13 can be employed as a potential drug for glaucoma with cataracts to delay the progression of cataracts.

Cataracts Associated With Fibroblast Growth Factor Receptor Inhibitors for Cholangiocarcinoma

Since fibroblast growth factor receptor inhibitors (FGFRi) are used for treatment of intrahepatic cholangiocarcinoma (iCCA), understanding potential complications following longer-term use in clinical practice settings is warranted. This study describes cataract formation or progression as a complication of FGFRi use for the treatment of iCCA, even after treatment discontinuation. To describe cases of cataract formation or worsening in patients with iCCA treated with FGFRi and to characterize the ophthalmologic features, risk factors, and outcomes for FGFRi-associated cataracts. This retrospective case series study used data from patients with iCCA harboring FGFR2 aberrations who received FGFRi in clinical trials or as standard therapy from the University of California, San Francisco, Hepatobiliary Tissue Bank and Registry. Data were collected from patient visits between February 2015 and October 2021, and this retrospective investigation was conducted from September 6, 2022, to May 4, 2023. Data analysis was conducted from May 5, 2023, to September 6, 2023. Use of an FGFRi for the treatment of iCCA. The primary outcome was designated as development of a new or worsening cataract after FGFRi initiation. Statistical analysis for the association between cataract formation and clinical covariates was performed using unpaired t tests and Fisher exact tests. A single bivariate logistic regression model was used to examine total duration of FGFRi therapy and age at the conclusion of FGFRi therapy as predictors of cataract development. A total of 18 patients were included in the study; median (range) patient age was 54 (27-81) years, and 13 patients (72%) were female. Nine patients (50%) developed a cataract or had cataract progression in at least 1 eye after initiation of FGFRi. Of 17 eyes with cataract, 8 eyes (47%) required cataract surgery. One patient rapidly developed a cataract associated with phacomorphic glaucoma, which required urgent surgery. The median (range) time to cataract onset or worsening from initiation of FGFRi was approximately 18 (1-23) months. Five of 9 patients (56%) who developed cataracts or had cataract progression were diagnosed with new or worsening cataracts after discontinuation of FGFRi. Patients who developed cataracts had longer median (range) duration of FGFRi treatment compared with patients who did not develop cataracts (13 months [2-26] vs 5 months [1-11]; odds ratio, 1.01; 95% CI, 1.00-1.02; P = .02). While this retrospective case series study cannot prove cause and effect conclusively due to the study design, study results highlight cataract formation or progression as a potential adverse effect of FGFRi therapy, supporting consideration of periodic eye examinations in patients who have received this treatment.

Facile fabrication of redox nanoparticles loaded with exosomal-miRNAs and resveratrol as glycation inhibitor in alleviating the progression and development of diabetic cataract.

Diabetic cataract (DC) represents a highly prevalent ocular manifestation resulting from diabetes often culminating in vision impairment among individuals with diabetes. Regrettably, the armamentarium of pharmaceutical interventions capable of both delaying and thwarting the onset of DC remains conspicuously sparse. Based on contemporary investigations, the pathogenesis of DC is prominently influenced by oxidative harm to the crystalline lens and the nonenzymatic glycosylation of lens proteins. Consequently, we have developed self-regenerating cerium oxide nanoparticles (CeO2 NPs), enveloped with resveratrol (RSV) and exosomal-microRNA (miRNA) to alleviate the effects of DC in an in vitro model. Moreover, the inclusion of RSV within CeO2 NPs serves a dual purpose. It can act as an antioxidant, minimizing glycation, and induce oxidative stress by effectively neutralizing reactive oxygen species (ROS). Additionally, it serves as a glycation inhibitor effectively preventing the cross-linking. Consequently, it helps minimize the glucose level in hemoglobin and inhibits the formation of advanced glycation end products (AGEs). Likewise, the CeO2-exosomal-miRNA when treated alone found to slightly impede the viability of human lens epithelial cells (HLEC) and induce apoptosis by suppressing the expression of α-crystalline gene (CRYAA). Particularly, miRNAs target genes associated with oxidative stress pathways, protein glycation, and the generation of AGEs, hence preventing structural damage to lens proteins. Compared with CeO2, RSV-CeO2, and miRNA-RSV-CeO2, the presence of miRNA-RSV-CeO2 led to a significant decrease in hemoglobin glycation. Remarkably, miRNA-RSV-CeO2 NPs attenuate the formation of malondialdehyde (MDA) and conjugated dienes (CD) with a relative value of 14.63 and 11.37nmol/mg. As per the report, this method presents a promising opportunity to implement the proposed material combination for attenuating diabetic cataracts.

Delayed-onset spontaneous bilateral Descemet’s membrane detachment after uneventful phacoemulsification

A 69-year-old male presented with defective vision in both eyes. Best corrected visual acuity (BCVA) was 6/6 p with anterior cortical and posterior subcapsular cataracts in both eyes. Fundus examination was normal. He underwent successful phacoemulsification with intraocular lens implantation in the left eye, improving BCVA to 6/6. Two months later, BCVA in the right eye decreased to 6/12p; cataract progression was noted. Phacoemulsification in the right eye restored BCVA to 6/6. Four months post-left eye surgery, he developed corneal edema with descemet membrane detachment (DMD). Multiple descemetopexies with SF6 led to reattachment. Right eye also developed DMD which reattached with SF6 descemetopexy. Final visual acuity was 6/6 in the right eye and 6/6 partial in the left eye.

METTL3-mediated m6A modification of SIRT1 mRNA affects the progression of diabetic cataracts through cellular autophagy and senescence

BackgroundThe increasing incidence of diabetes mellitus has established diabetic cataracts (DC) as a significant worldwide public health issue. The mechanisms underlying DC remain unknown, and effective prevention and treatment strategies are lacking. Accordingly, we aimed to explore the role and mechanism behind N6-methyladenosine (m6A) in DC progression.MethodsMethyltransferase-like 3 (METTL3), p21, Beclin1, LC3, and p62 expression levels were measured in human tissues. This study assessed total m6A levels and common m6A-regulated biomarkers in both in vitro and in vivo DC models. Autophagy flux was detected in vitro through Ad-mCherry-GFP-LC3B and Monodansylcadaverine (MDC) staining. Cellular senescence was assessed utilizing the senescence-associated β-galactosidase (SA-β-Gal) assay. Furthermore, the effect of METTL3 on SIRT1 mRNA modification was demonstrated, and its mechanism was elucidated using RT-qPCR, western blot, RNA stability assays, and RIP analysis.ResultsMETTL3, p21, and p62 expression levels were elevated in lens epithelial cells (LECs) from DC patients, while Beclin1 and LC3 levels were reduced. Silencing METTL3-mediated m6A modifications restored high-glucose-induced autophagy inhibition and prevented premature senescence in LECs. Notably, SIRT1720 and Metformin significantly enhanced autophagosome generation and delayed cellular senescence. The m6A-reading protein YTHDF2 bound to m6A modifications, and YTHDF2 silencing significantly reduced METTL3-mediated SIRT1 inactivation.ConclusionsMETTL3 induces senescence in DC by destabilizing SIRT1 mRNA in an m6A-YTHDF2-dependent manner. The METTL3-YTHDF2-SIRT1 axis is a key target and potential pathogenic mechanism in DC.

Association between systemic immune-inflammation index and cataract among outpatient US adults.

While several studies have noted a higher SII correlates with multiple diseases, research on the association between SII and cataract remains limited. Our cross-sectional study seeks to examine the association between SII and cataract among outpatient US adults. This compensatory cross-sectional study utilized NHANES data from 1999 to 2008 cycles, conducting sample-weighted multivariate logistic regression and stratified analysis of subgroups. Among 11,205 adults included in this study (5,571 [46.2%] male; 5,634 [53.8%] female), 2,131 (15.2%) had cataract and 9,074 (84.8%) did not have cataract. A fully adjusted model showed that SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts among women (OR, 1.27; 95% CI, 1.02-1.59) (p = 0.036). However, no difference was found in the men subgroup, and there was no significant interaction between SII and sex. Our results indicated that a SII higher than 500 × 109/L was positively correlated with an increased risk of cataracts in women. This study is the first to specifically investigate the impact of a high SII on cataract risk in outpatient adults in the United States. By effectively addressing inflammation, it is possible to mitigate cataract progression and significantly enhance patient outcomes.

Effectiveness Of Planned Teaching Programme On Preventive Measures Of Cataract Among Adults In Selected Urban Community, Mangalore

A cataract is the clouding of the lens in the eye affecting vision. Early in the development of age-related cataract the power of the lens may be increased, causing near-sightedness (myopia), and the gradual yellowing and opacification of the lens may reduce the perception of blue colours. Most cataracts are related to aging. Exposure to sunlight may be associated with an increased risk of cataract. Vitamin supplements have shown varying results in delaying the progression of cataract. Globally, there are nearly 45 million blind people. Almost 135 million people are with low vision. A total of nearly 180 million people have some degree of visual disability. Nine of the ten who are blind live in the developing countries. On the current projections, there could be estimated 50 million blind people due to cataract by 202016. Prevalence of cataract in USA is approximately 5.5 million or 2.02%. India is one of the countries that have a sizeable number of visually impaired people17 . The annual incidence of cataract blindness in India is about 3.8 million. Statistics reveal that over 12 million people in the country are visually handicapped. Out of 41.8% of global blindness, 23.5% is contributed by India. Major proportion of total blindness in India (81%) is constituted by cataract18 . In Karnataka prevalence of cataract blindness among the men above the age of fifty is 3.39% and women is 6.51%, in Dakshina Kannada district it is 1.27% for men and 7.65% for women19 . Hence the researcher felt the need to evaluate the effectiveness of planned teaching programme on preventive measures of cataract in a selected urban community, Mangalore. Objectives: The purpose of this study was • to determine the level of knowledge on preventive measures of cataract among adults as measured by a structured closed-ended knowledge questionnaire • to determine the effectiveness of Planned Teaching Programme on preventive measures of cataract among adults • to find the association between the pre-test knowledge scores with selected demographic variables. Research approach and design: A pre-experimental research design of one group pre- and post-test with an evaluative approach was used for this study. Setting: The study was conducted in Jeppu urban community area of Mangalore. Subjects: Adults in the age group of 30-55 years in the selected urban areas of Mangalore Sample size and Sampling technique: The sample for the present study comprised 100 adults in the age group of 30-55 years who met the inclusion criteria The investigator purposely selected the adults who were judged to be a typical population who needs the knowledge related to cataract. Planned teaching programme The planned teaching programme on “preventive measures of cataract.” was developed after an exhaustive review. The content the planned teaching programme included • Introduction • Definition • Eye and lens • Functions of eye • Definition of cataract • Incidence of cataract • Etiological risk factors of cataract • Classification of cataract • Sites of cataract • Clinical manifestations of cataract • Diagnostic measures of cataract • Preventive measures of cataract • Therapeutic regimen in case of diabetes and hypertension • Demonstrate the eye exercises • Conclusion Instrument used: Structured closed-ended knowledge questionnaire on preventive measures of cataract among adults. The data was analysed using descriptive statistics and inferential statistics Major findings and reports: Descriptive and inferential statistics were used to analyse the data. Pre-test assessment revealed that highest percentage (49%) of adults had poor knowledge, 43% had average knowledge, and only 8% had good knowledge. The post-test revealed that 98% had gained very good knowledge, 2% of them gained good knowledge. The total mean percentage of pre-test knowledge score was 43.58% (mean 10.46 ± 3.22) and the mean percentage post-test knowledge score was 92.25% (mean 22.14 ± 1.38) showing an effectiveness of 48.62% (mean 11.68± 2.89). Significance of difference between pre-test and post-test was statistically tested by using paired ‘t’ test and it was found very highly significant (t=40.10, p<0.05). The pretest knowledge score showed association between the pre-test knowledge and previous source of information regarding prevention of cataract but there was no association between pre-test knowledge and age, gender, educational status, occupation and family history of cataract. Conclusion: The findings of the study reveal that adults had inadequate knowledge on preventive measures of cataract; however the knowledge has significantly improved after the Planned Teaching Programme. Hence, it is concluded that PTP was highly effective in improving the knowledge of the adults regarding the preventive measures of cataract.

The Impact of Smoking and Hypertension on Cataract Development in Diabetic Patients

Background Cataracts are a leading cause of visual impairment and blindness globally, with a particularly high incidence in diabetic patients due to the complex interplay of metabolic dysregulation and hyperglycemia-induced oxidative stress. Diabetic cataract development is influenced by several modifiable risk factors including smoking and hypertension, which may exacerbate lens opacity through various biological mechanisms. This study aims to determine the effects of smoking and hypertension on cataract development in diabetic patients. Methods Conducted from December 2022 to November 2023, this cross-sectional study at a specialized diabetes and ophthalmology healthcare facility involved 60 diabetic patients. The participants were divided into two groups: those with cataracts (n=32) and those without (n=28). Data collection focused on demographics, smoking history, hypertension status, and cataract presence, using structured interviews and medical record reviews. Logistic regression was employed to analyze the association between cataracts and potential risk factors, adjusting for age, diabetes duration, and glycemic control. Results Age and genderfi were not significantly different between the two groups, with mean ages of 50.21±14.34 years in the cataract group and 49.41±12.15 years in the non-cataract group (P=0.087). The prevalence of smoking was similar between those with cataracts (14.3%) and without (15.6%), showing no significant association (P=0.885). Hypertension was more prevalent in the cataract group (71.4%) compared to the non-cataract group (53.1%), although this difference was not statistically significant (P=0.146). Logistic regression analysis indicated that smoking had a minimal effect on cataract development (OR=1.187; 95% CI=0.264-5.33; P=0.823), and while hypertension showed a stronger association (OR=2.277; 95% CI=0.749-6.92), it also lacked statistical significance (P=0.147). Conclusion Neither smoking nor hypertension showed significant associations with cataract development. These findings suggest that the influence of these factors on cataract progression may differ in diabetic individuals due to the complex interplay of metabolic and vascular changes associated with the condition.

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

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

Vitrectomy versus scleral buckle for retinal detachment without posterior vitreous detachment

To compare the effectiveness and safety of scleral buckling and pars plana vitrectomy in treating retinal detachment without posterior vitreous detachment. A total of 88 eyes of 83 patients with retinal detachment without prior posterior vitreous detachment were investigated retrospectively. Group A comprised patients who underwent scleral buckling (n = 47) and Group B (n = 36) patients who were treated with pars plana vitrectomy. Anatomical success, postoperative visual acuity, and ocular adverse events were evaluated. The primary and final anatomical success rate showed a nonsignificant difference (p = 0.465 and p = 0.37 respectively). No significant difference was observed in the reoperation rate or development of epiretinal membrane between the groups (p = 0.254 and p = 0.254 respectively). However, scleral buckling resulted in significantly better visual acuity at the last follow-up (0.12 ± 0.23) compared to pars plana vitrectomy (0.37 ± 0.46, p = 0.001). The incidence of cataract progression was also significantly higher in the pars plana vitrectomy group (46%) compared to the scleral buckling group (10%, p < 0.001). Scleral buckling and pars plana vitrectomy show similar success rates in treating retinal detachment without vitreous detachment. However, due to less cataract progression and better visual acuity outcomes, scleral buckling is recommended for these cases. Determining vitreous status before surgery is crucial for optimal outcomes.

Metabolic changes in the eye lens in the progression of cataract

Background. Cataract is one of the main causes of decreased visual acuity in the world, and therefore scientists are continuing researches on the mechanisms of development of this ophthalmic pathology.The aim. To study metabolic changes in a cloudy lens using an experimental model.Materials and methods. The study was carried out on adult male Wistar rats (n = 60), which were divided into control (n = 30) and experimental (n = 30) groups. Experimental cataract were simulated by daily ultraviolet irradiation (λ = 300–350 nm) during 6 months for 20 minutes. At the months 2, 4 and 6 of the study, we carried out a biomicroscopic examination of the anterior eye of animals using a slit lamp to monitor the development of cataract. Lenses were collected to determine the content of stearoyl-coenzyme-A desaturases and melatonin using enzyme immunoassay.Results. At the stage of initial cataract, the content of the stearoyl-coenzyme A desaturase was statistically significantly lower than the control values by 38 %; at the stage of immature cataract – by 30 %; at the stage of mature cataract – by 15.4 %. It was revealed that at the month 6 of the study, the concentration of melatonin in lens homogenates was 17 % lower when compared with the control. A statistically significant correlation was established between stearoyl-coenzyme A desaturase and melatonin (r = 0.32).Conclusion. Melatonin and stearoyl-coenzyme A desaturase play an important role in a number of biochemical processes that ensure the proper functioning of the visual analyzer. Changes in the concentration of these biological molecules can play a key role in the pathogenesis of cataract and a number of other ophthalmic diseases

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

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

Comparing the efficacy of dexamethasone implant and anti-VEGF for the treatment of macular edema: A systematic review and meta-analysis.

To evaluate the clinical efficacy of dexamethasone (DEX) implant, for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic retinopathy (DR) through a systematic review and meta-analysis. The PubMed, Embase and Cochrane Library databases were comprehensively searched from inception to November 21, 2022, for studies evaluating the clinical efficacy of DEX implant for patients with retinal vein occlusion macular edema (RVO-ME) or diabetic macular edema (DME). Randomized controlled trials (RCTs) published in English were considered eligible. The Cochrane Collaboration tool was applied to assess the risk of bias in each study. Effect estimates with 95% confidence intervals (CIs) were pooled using the random effects model. We also conducted subgroup analyses to explore the sources of heterogeneity and the stability of the results. This meta-analysis included 8 RCTs (RVO-ME [n = 2] and DME [n = 6]) assessing a total of 336 eyes. Compared with anti-VEGF therapy, DEX implant treatment achieved superior outcomes in terms of best corrected visual acuity (BCVA) (mean difference [MD] = -3.68 ([95% CI, -6.11 to -1.25], P = 0.003), and no heterogeneity was observed (P = 0.43, I2 = 0%). DEX implant treatment also significantly reduced central macular thickness (CMT) compared with anti-VEGF treatment (MD = -31.32 [95% CI, -57.92 to -4.72], P = 0.02), and there was a high level of heterogeneity between trials (P = 0.04, I2 = 54%). In terms of severe adverse events, DEX implant treatment had a higher risk of elevated intraocular pressure than anti-VEGF therapy (RR = 6.98; 95% CI: 2.16 to 22.50; P = 0.001), and there was no significant difference in cataract progression between the two groups (RR = 1.83; 95% CI: 0.63 to 5.27, P = 0.31). Compared with anti-VEGF therapy, DEX implant treatment is more effective in improving BCVA and reducing ME. Additionally, DEX implant treatment has a higher risk of elevated intraocular pressure. Due to the small number of studies and the short follow-up period, the results should be interpreted with caution. The long-term effects of the two treatments need to be further determined. Prospero Registration Number CRD42021243185.

Metabolomic Disparities in Intraocular Fluid Across Varied Stages of Cataract Progression: Implications for the Analysis of Cataract Development.

Introduction: The lens's metabolic demands are met through a continuous circulation of aqueous humor, encompassing a spectrum of components such as organic and inorganic ions, carbohydrates, glutathione, urea, amino acids, proteins, oxygen, carbon dioxide, and water. Metabolomics is a pivotal tool, offering an initial insight into the complexities of integrated metabolism. In this investigative study, we systematically scrutinize the composition of intraocular fluid in individuals afflicted with cataracts. Methods: The investigation involved a comprehensive analysis of aqueous humor samples from a cohort comprising 192 patients. These individuals were stratified by utilizing the SPONCS classification system, delineating distinct groups characterized by the hardness of cataracts. The analytical approach employed targeted quantitative metabolite analysis using HILIC-based liquid chromatography coupled with high-resolution mass spectrometric detection. The metabolomics data analysis was performed with MetaboAnalyst 5.0. Results: The results of the enrichment analysis have facilitated the inference that the discerned disparities among groups arise from disruptions in taurine and hypotaurine metabolism, variations in tryptophan metabolism, and modifications in mitochondrial beta-oxidation of short-chain saturated fatty acids and pyrimidine metabolism. Conclusion: A decline in taurine concentration precipitates diminished glutathione activity, prompting an elevated requirement for NAD+ and instigating tryptophan metabolism along the kynurenine pathway. Activation of this pathway is additionally prompted by interferon-gamma and UV radiation, leading to the induction of IDO. Concurrently, heightened mitochondrial beta-oxidation signifies a distinctive scenario in translocating fatty acids into the mitochondria, enhancing energy production.

Antiglycation Effect of Jabuticaba (Plinia cauliflora) and Its Potential Role in Delaying Cataract Formation in Streptozotocin-Induced Diabetic Rats

Jabuticaba fruit (Plinia cauliflora) is widely consumed in various forms such as juice, jam, wine, and liquors; however, its potential therapeutic effects on diabetic complications remain inadequately explored. We aimed to investigate the potential antiglycation activity of Jabuticaba, identify the active compounds through bioassay-guided fractionation, and assess its effects on cataract formation in a Streptozotocin-induced diabetic type 1 rat model. Through bioassay-guided fractionation, we identified gallic acid (IC50: 24.7 µg/mL), protocatechuic acid (IC50: 1.22 µg/mL), and an ellagitannin, Repandinin B (IC50: 0.55 µg/mL), as active compounds contributing to antiglycation effects. In the animal study, the addition of Jabuticaba juice extract to the drinking water at a concentration of 0.5% (w/v) for 12 weeks demonstrated an amelioration in cataract progression. These results suggest that Jabuticaba has high antiglycation effects leading to the delaying of cataract formation in type 1 diabetes.

Circular RNA Circ_0122396 Regulates Human Lens Epithelial Cell Progression by Regulating miR-23a-3p and MMP16 in Age-Related Cataract

Background CircRNA plays a regulatory role in multiple life processes. Circ_0122396 could participate in the regulation of age-related cataract (ARC) progression. However, the precise molecular mechanisms of circ_0122396 In ARC remain enigmatic. Methods Circ_0122396, microRNA (miR)-23a-3p, and matrix metalloprotease (MMP)-16 (MMP16) expression levels were detected via quantitative real-time polymerase chain reaction. Western blot was used to detect the levels of MMP16 and apoptosis-related proteins. Cell counting kit-8 analysis and 5-ethynyl-2’-deoxyuridine assay were used to assess human lens epithelial cells (HLECs) proliferation. Flow cytometry was performed to determine cell apoptosis. Levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were measured using commercial kits. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were used to examine the interaction among circ_0122396, miR-23a-3p, and MMP16. Results Circ_0122396 and MMP16 were down-regulated while miR-23a-3p was up-regulated in ARC. H2O2 constrained proliferation and GSH-PX level, promotes apoptosis and MDA level in HLECs, and overexpression of circ_0122396 attenuated these effects. miR-23a-3p was a direct target of circ_0122396, and MMP16 was a direct target of miR-23a-3p. The effect of circ_0122396 overexpression on H2O2-induced HLECs was reversed by miR-23a-3p, and MMP16 elevation overturned the impacts of miR-23a-3p in H2O2-induced HLECs. Conclusions Circ_0122396 may regulate the progression of ARC via the miR-23a-3p/MMP16 pathway in H2O2-stimulated HLECs, which may serve as a potentially valuable biomarker and novel therapeutic target for ARC.

Comparing ranibizumab, dexamethasone implant, and combined therapy for macular edema secondary to branch retinal vein occlusion: a clinical trial.

Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare the efficacy and safety of intravitreal ranibizumab (IVR) or dexamethasone implant (IDI) monotherapy, as well as the combination of IVR and IDI injections, in patients with ME secondary to branch retinal vein occlusion (BRVO). This multicenter, prospective, and comparative study included 292 patients with unilateral ME involvement (total of 292 eyes) secondary to BRVO. The patients were randomly assigned to three groups and followed up for 12months. Patients in group 1 (n = 96) were treated with 3-dose loading IVR injections followed by a pro re nata (PRN) regimen. Patients in group 2 (n = 98) received IVR combined with IDI injection, followed by IVR PRN regimen. Patients in group 3 (n = 98) were treated with IDI injection, followed by repeated IDI injection based on clinical necessity. Best corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and frequency of injections were recorded and compared between the three groups. At baseline, the three groups did not differ in age, gender, duration of ME, BCVA, IOP, and CRT (P > 0.05). Mean number of total injections per eye within 12months were 7.1 ± 2.3 (range 4-9) in group 1, 3.7 ± 1.5 (range 2-6) in group 2, and 1.8 ± 0.4 (range 1-3) in group 3. There was a statistical difference in the number of injections between group 1 and group 2 (P = 0.037). Eyes in group 3 received fewer injections than those in group 2, but the difference was not statistically significant (P = 0.052). BCVA improvement and CRT reduction were achieved in all groups and there was no significant difference between the three groups at the end of the 12th month. However, IOP elevation and cataract progression were more frequent in group 3, especially in those patients who received repeated IDI injections. Three therapeutic regimens had comparable efficacy in treating ME secondary to BRVO. Combination therapy had an advantage in maintaining good effect with fewer re-injections and complications. The study complied with the principles of the Declaration of Helsinki and was approved by Xi'an Aier Ancient City Eye Hospital, Xi'an Aier Eye Hospital, and Xianyang Aier Eye Hospital ethics committees (2022SF-367).

Be aware of cataracts following Pars Plana Vitrectomy (PPV): what should be considered?

Background: Pars Plana Vitrectomy (PPV) is a vitreoretinal surgical technique that allows access to the posterior part of the eye, with an average of 225,000 vitrectomies performed annually in the United States. However, there is an incline with the number of cataract formation as a complication following PPV surgery. In a study in the UK involving 2000 eyes after the PPV procedure, the risk of cataracts was found to be 40%, and 52% of patients would undergo cataract surgery within the first year. The development of cataracts after PPV is associated with several risk factors; however, the risk factors for developing cataracts are still unclear. Therefore, a systematic review was conducted regarding the risk factors for developing cataracts after PPV. Methods: This systematic review followed the Preferred Reporting Items of Systematic Reviews (PRISMA) guidelines. Studies were identified through an electronic systematic search of PubMed, Embase (Elsevier), Cochrane Central (Wiley), Scopus (Elsevier), manual searching, and ClinicalTrials.gov. The search keywords used were related to “cataract”, “pars plana vitrectomy”, and “risk factor” using the Boolean operator AND and OR. We limited the studies from 2013 until 2023. All studies that discussed cataract risk factors after PPV surgery using English language will be included. Result: From 495 studies, based on inclusion and exclusion criteria, we included 6 studies with a total sample of 2.902 eyes. Risk factors associated with cataracts after PPV surgery were preoperative (older age, RRD with involvement of macular, lens status) and intraoperative (type of tamponade). It took 24 months after PPV surgery for the patient to undergo cataract surgery. Conclusion: Preoperative conditions and surgical intervention might affect the formation and progression of cataracts. Therefore, an ophthalmologist should consider several risk factors for cataract formation after PPV.

Mir-204-5p alleviates mitochondrial dysfunction by targeting IGFBP5 in diabetic cataract.

Cataract contributes to visual impairment worldwide, and diabetes mellitus accelerates the formation and progression of cataract. Here we found that the expression level of miR-204-5p was diminished in the lens epithelium with anterior lens capsule of cataract patients compared to normal donors, and decreased more obviously in those of diabetic cataract (DC) patients. However, the contribution and mechanism of miR-204-5p during DC development remain elusive. The mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model. Our results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC.

The effect of intravitreal cidofovir injection on end-stage glaucoma in dogs: a retrospective study of 153 eyes.

To evaluate the long-term efficacy, prognostic factors, and complications of intravitreal cidofovir injection in dogs with end-stage glaucoma. 130 client-owned dogs. Medical records of dogs that underwent intravitreal cidofovir injections were reviewed. A minimum follow-up period of 6 months was required as the inclusion criterion. Signalment, type of glaucoma, preinjection intraocular pressure (IOP), types of applied glaucoma eye drop, coexisting ocular diseases, outcomes, and complications were recorded. Success was defined as IOP of ≤ 25 mm Hg at the 2-week recheck that remained to the 6-month recheck. The overall success rate of intravitreal cidofovir injection was 91.5% (140/153). The success rate of a single injection was 69.3% (106/153), of a second injection was 59.5% (25/42), of a third injection was 42.9% (6/14), of a fourth injection was 33.3% (2/6), and of a fifth injection was 50.0% (1/2). Intraocular pressures at 6 months after injection were relatively higher when the injection was repeated, fewer types of glaucoma eye drop were applied prior to the injection, and cataract stages were advanced at the time of injection (P < .05). The most common complications were phthisis bulbi (42.5%), cataract progression (30.1%), and intraocular hemorrhage (16.3%). Six eyes were enucleated, and 3 were enucleated due to corneal perforation. Intravitreal cidofovir injection had a high long-term success rate in lowering IOP in dogs with end-stage glaucoma.