Application of transgenic mice to the molecular pathogenesis of cataract

One of the most prevalent disorders that cause blindness worldwide is cataract,and its essence is the visual disorder caused by the opacity of the lens.The significant degree of variation in cataracts and the fact that a variety of factors can impact a patient’s lens transparency make it especially crucial to investigate the pathogenesis of cataracts at the molecular level.It has been found that more than 60 genes are linked to the formation of cataracts,and the construction of a transgenic mouse model of cataract similar to the selection of human lens clouding due to a variety of causes has become an important means of studying the pathogenesis of cataract.Therefore,the research on the application of transgenic mice to the molecular pathogenesis of cataracts will be the main topic of this review of the literature.

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the axon.TAU is missorted and aggregated in an array of diseases known as tauopathies.Microtubules are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing enzymes.As impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule dynamics.We therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to microtubules.To investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic littermates.In sum,P301L-TAU results in changes in microtubule PTMs,suggestive of impairment of microtubule stability.This is accompanied by missorting and aggregation of TAU in mice but not in i Neurons.Microtubule PTMs/impairment may be of key importance in tauopathies.

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

Analysis of Ultrasonic Emulsification Surgery and Small Incision Cataract Extracapsular Extraction Surgery for Cataract Clinical Treatment Level Improvement

Objective:To analyze the efficacy of ultrasonic emulsification and small incision cataract extracapsular extraction in cataract patients.Methods:96 cataract patients admitted from May 2021 to May 2023 were selected and randomly grouped into group A(ultrasonic emulsification)and group B(small-incision extracapsular cataract extraction),with 48 cases each.Results:At 1 week,1-month,and 3 months post-operation,the visual acuity of group A was higher and the astigmatism value was lower than that of group B(P<0.05);at 12h,24h,and 48h post-operation,the intraocular pressure of group A was higher than that of group B(P<0.05);the thickness of macular area of group A was lower than that of group B at 1 week and 1-month post-operation(P<0.05).Conclusion:Ultrasonic emulsification in cataract patients was slightly better than small incision cataract extracapsular extraction in correcting astigmatism,improving visual acuity,and regulating macular thickness.However,due to the high energy of ultrasonic emulsification,the risk of complications such as high postoperative intraocular pressure was higher.Small-incision extracapsular cataract extraction has better application value in economically disadvantaged areas.

Characterization of N6-methyladenosine long non-coding RNAs in sporadic congenital cataract and age-related cataract

AIM:To characterize the N6-methyladenosine(m6A)modification patterns in long non-coding RNAs(lncRNAs)in sporadic congenital cataract(CC)and age-related cataract(ARC).METHODS:Anterior capsule of the lens were collected from patients with CC and ARC.Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs.RESULTS:Large amount of m6A peaks within lncRNA were identified for both CC and ARC,while the level was much higher in ARC(49870 peaks)than that in CC(18688 peaks),yet those difference between ARC in younger age group(ARC-1)and ARC in elder age group(ARC-2)was quite slight.A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs,as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC.On the other hand,5893 hypermethylated and 5213 hypomethylated lncRNAs,as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1.Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles,as well as nucleotide excision repair.CONCLUSION:Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC,providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Effect of sequential nursing care combined with communication intervention on visual recovery and pain after cataract ultrasound emulsification

BACKGROUND Cataracts are a common ophthalmic disease and postoperative vision recovery is crucial to patient quality of life.Rational and efficient care models play an impor-tant role in promoting vision recovery.AIM To evaluate the clinical effectiveness of procedural nursing care combined with communication intervention in vision recovery after cataract ultrasound emulsi-fication.METHODS A randomized controlled study was conducted on 100 patients with cataracts who underwent ultrasound emulsification surgery.They were randomly assigned to an experimental group or a control group.The experimental group received procedural nursing combined with Connect,Introduce,Communicate,Ask,Respond,Exit(CICARE)communication intervention,whereas the control group received conventional nursing.The effectiveness of the nursing model was assessed by comparing differences in vision recovery,pain scores,and mental health status between the two groups.RESULTS It was found that over time the visual acuity of patients in both groups gradually recovered and patients in the experimental group had lower pain scores and superior mental health status than the control group(P<0.05).CONCLUSION Procedural nursing combined with CICARE communication intervention has positive effects on vision recovery in patients after cataract ultrasound emulsification.

Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice

With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

Resolution of myopic macular schisis following cataract phacoemulsification

Dear Editor,We write to introduce a case of high myopia who had bilateral macular schisis along with cataracts.During the following-up period from 2014 to 2021,the severity of macular schisis gradually worsened.However,following cataract surgery,there was a gradual improvement in the macular schisis,ultimately leading to near-complete resolution.We obtained the written informed consent from the patient,and this case study adhered to the principles in the Declaration of Helsinki.

Are there sex-based disparities in cataract surgery?

AIM:To investigate sex-based differences in the occurrence of intra-operative and post-operative complications and associated visual outcomes following cataract surgery.METHODS:This was a retrospective study of patients who had phacoemulsification cataract surgery at the University of Colorado School of Medicine.Data collected included the patient’s health history,ocular comorbidities,operative and post-operative complications,and the post-operative best corrected visual acuity(BCVA).The data were analyzed using univariate and multivariable logistic regression with generalized estimating equations to account for the correlation of some patients having two eyes included in the study.RESULTS:A total of 11977 eyes from 7253 patients were included in the study.Ocular comorbidities differed by sex,with males having significantly higher percentages of traumatic cataracts(males 0.7%vs females 0.1%),prior ocular surgery(6.7%vs 5.5%),and mature cataracts(2.8%vs 1.9%).Conversely,females had significantly higher rates of pseudoexfoliation(2.0%vs 3.2%).In unadjusted analysis,males had higher rates of posterior capsular rupture(0.8%vs 0.4%)and vitreous loss(1.0%vs 0.6%),but this difference was not significant after adjustment for confounders.Males had a significantly increased risk of post-operative retinal detachment,but in multivariable analysis this was no longer significant.Males were significantly less likely to undergo post-operative neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy for posterior capsule opacification(OR=0.8,95%CI=0.7-0.9,P=0.0005).The BCVA was slightly worse for males pre-operatively;but post-operatively,both sexes exhibited similar visual acuity of Snellen equivalent 20/25.CONCLUSION:The study finds that in a cohort of patients presenting for cataract surgery,sex differences exist in pre-operative comorbidities and surgical characteristics that contribute to higher rates of some complications for males.However,observed surgical complication rates exhibit almost no difference by sex after adjusting for pre-operative differences and post-operative BCVA is similar between sexes.

Research progress on the correlation between aqueous humor components and pathogenesis and postoperative complications in patients with different types of cataracts

Aqueous humor provides the necessary nutrition for the lens and transports the metabolites in the eye.It was a liquid that can directly reflect the microenvironment in the eye'and it can be easily obtained during the operation.This review intended to analyze the components of aqueous humor in patients with different types of cataracts'so as to reflect the pathogenesis and development of the disease'evaluate the incidence of postoperative complications and provide reference value for the surgical design of sequential cataract surgery.The aqueous humor components of different types of cataracts showed different degrees of inflammation'oxidative stress and extracellular matrix remodeling.The biomarker of early neuropathy in diabetic cataract was neural cell adhesion molecule-1(NCAM1).Transforming growth factor-β(TGF-β)was the evaluation factor of disease development in patients with pseudoexfoliation syndrome.The relationships between postoperative complications of different types of cataracts and aqueous humor components were as follows:Macular edema after diabetic cataract surgery was associated with tumor necrosis factor-alpha;capsular contraction after high myopic cataract surgery was related to monocyte chemoattractant protein-1(MCP-1)and TGF-β2;Klotho and glutathione S-transferase P 1(GSTP1)were associated with high intraocular pressure after primary open-angle glaucoma complicated by cataract surgery;capsular contraction after retinitis pigmentosa complicated by cataract surgery was associated with matrix metalloproteinases;pro-inflammatory cytokines and fibroblast growth factor 4 in the aqueous humor of congenital cataracts were associated with posterior capsular opacification after surgery.Granulocyte colony stimulating factor 3 and MCP-1 were the main cytokines mediating the pain of the second eye in the binocular sequential cataract surgery short interval(1 wk)'while MCP-1 mediated pain in the long interval(6 wk).The second eye after binocular sequential cataract surgery had a higher level of proinflammatory factors.The components of aqueous humor in patients with different types of cataracts were related to the pathogenesis and postoperative complications of the disease.Monitoring the components of the aqueous humor could help better understand the intraocular microenvironment of different types of cataracts and provide a reference for predicting the development of the disease and implementing relevant targeted therapy.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract

AIM:To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity.METHODS:A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited.Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals.Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery.The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2(EPHA2).Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins.The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction(qRT-PCR)and Western blotting assay,respectively.The cell migration was analyzed by wound healing assay.Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo.RESULTS:A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif(SAM)domain of EPHA2.Functional studies demonstrated the variant’s impact:reduced EPHA2 protein expression,altered subcellular localization,and disrupted interactions with other lens membrane proteins.This mutant notably enhanced human lens epithelial cell migration,and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast(DIC)optics.CONCLUSION:Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes

●AIM:To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes.●METHODS:Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited.Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients’medical records.A hierarchical cluster analysis was performed.The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts.●RESULTS:A total of 164 children(299 eyes)were divided into two clusters based on their ocular features.Cluster 1(96 eyes)had a shorter axial length(mean±SD,19.44±1.68 mm),a low prevalence of macular abnormalities(1.04%),and no retinal abnormalities or posterior cataracts.Cluster 2(203 eyes)had a greater axial length(mean±SD,20.42±2.10 mm)and a higher prevalence of macular abnormalities(8.37%),retinal abnormalities(98.52%),and posterior cataracts(4.93%).Compared with the eyes in Cluster 2(57.14%),those in Cluster 1(71.88%)had a 2.2 times higher chance of good best-corrected visual acuity[<0.7 logMAR;OR(95%CI),2.20(1.25–3.81);P=0.006].●CONCLUSION:This retrospective study categorizes congenital cataracts into two distinct clusters,each associated with a different likelihood of visual outcomes.This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit,thereby making strides toward precision medicine in the field of congenital cataracts.

Combinative approach of transzonular triamcinolonemoxifloxacin and perioperative drops to minimize postoperative complications of cataract surgery

AIM: To investigate the effectiveness of combinationtherapy with transzonular triamcinolone-moxifloxacin andconventional perioperative drops in reducing postoperativecomplications of cataract surgery. METHODS: Electronic medical records of cataractsurgery patients (single surgeon) were reviewed fromJanuary 2018 to September 2021. The rate of postoperativecomplications including prolonged and/or recurrentpostoperative inflammation, endophthalmitis, cystoid macularedema (CME), and intraocular pressure (IOP) was comparedbetween the patients receiving combinative therapy andpatients receiving drops only. RESULTS: Totally 596 patients and 1057 eyes(Combinative-Therapy group 493 and Drop-Only group 564)were included in this study. Using combination therapyreduced the relative risk of postoperative inflammationby 26.9% (16.6% Combinative-Therapy vs 22.7% Drop-Only, P=0.013). The incidence of endophthalmitis was 0in Combinative-Therapy group vs 0.5% in Drop-Only group(relative risk reduction 100%), although not statisticallysignificant (P=0.10). The incidence of severe IOP spikeswas not significantly different between Combinative-Therapy (2.4%) and Drop-Only (1.6%) groups (P=0.33).The relative risk of postoperative CME was 51.4% less inthree months follow up visit in Combinative-Therapy group,although not statistically significant (P=0.07). The visualoutcome 1-month postop. (best corrected visual acuity) wassignificantly better in Combinative-Therapy (logMAR 0.10)compared to Drop-Only (logMAR 0.14) groups (P=0.02) whilethe baseline visual acuity was not significantly different. CONCLUSION: The combinative approach oftranszonular triamcinolone-moxifloxacin plus perioperativeeyedrops is an effective method to minimize postoperativeinflammation, with better visual outcomes. It couldpotentially reduce the risk of postoperative endophthalmitisand CME (near-significant P-values;larger studies couldanalyze better considering low incidence).

Novel MIP gene mutation causes autosomal-dominant congenital cataract

●AIM:To identify disease-causative mutations in families with congenital cataract.●METHODS:Two Chinese families with autosomaldominant congenital cataract(ADCC)were recruited and underwent comprehensive eye examinations.Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family.Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis.The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis.Major intrinsic protein(MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos.Zebrafish embryonic lens phenotypes were screened using confocal microscopy.●RESULTS:A novel heterozygous mutation(c.85G>A;p.G29R)in the MIP gene was identified in the proband of one family.A known heterozygous mutation(c.97C>T;p.R33C;rs864309693)in MIP was found in the proband of another family.In-silico prediction indicated that the novel mutation might affect the MIP protein function.Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP.●CONCLUSION:Two missense mutations in the MIP gene in Chinese cataract families are identified,and one of which is novel.These findings expand the genetic spectrum of MIP mutations associated with cataracts.The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

Modeling monocular form deprivation in rabbits using a simulated-cataract intraocular lens

AIM:To establish an animal model of form deprivation amblyopia based on a simulated cataract intraocular lens(IOLs).METHODS:Poly(dimethyl siloxane)-SiO_(2) thin films(PSF)with different degrees of opacity as IOL materials were prepared.The light transmission of the PSF-IOL was measured,and its in vitro biosafety was determined by cell counting kit(CCK)-8 assay using the HLEC-B3 cell line and ARPE-19 cell line.Subsequently,the in vivo safety was determined by implanting the PSF-IOL with 10%wt SiO_(2) into the right eyes of New Zealand white rabbits(PSF-IOL group),and compared with two control groups:contralateral comparison group and normal control(NC)group(Contralateral comparison group:the fellow eye;NC group:a group of binocular normal rabbits without intervention).The flash visual-evoked potentials(F-VEPs)were measured to verify amblyopia.RESULTS:PSFs containing 0,2%,and 10%wt SiO_(2) were successfully constructed.The 0 SiO_(2) PSF was transparent,while the 10%wt SiO_(2) PSF was completely opaque.It was found that PSF did not induce unwanted cytotoxicity in HLECs and ARPE19 cells in vitro.In vitro,PSF-IOL with 10%wt SiO_(2) was also non-toxic,and no significant inflammation or structural changes occurred after four weeks of PSF-IOL implantation.Finally,our IOL-simulated congenital cataract rabbit detected by F-VEPs suggested tentative amblyopia.CONCLUSION:A PSF-IOL that mimics cataracts is created.A novel form deprivation model is created by the IOL-simulated congenital cataract rabbit.It can be developed fast and stable and holds great potential for future study.

Comparison of ocular biometric parameters between two swept-source optical coherence tomography devices and Scheimpflug tomography in patients with cataract

AIM:To assess and compare the variations and agreements across different ocular biometric parameters using swept-source optical coherence tomography(SS-OCT)and Scheimpflug tomography in patients diagnosed with cataract.METHODS:This prospective case series was conducted at Tianjin Medical University Eye Hospital.In total,212 eyes from 212 patients scheduled for phacoemulsification were included.Eyes were evaluated preoperatively using two SSOCT devices(IOLMaster700 and CASIA2)and Scheimpflug tomography(Pentacam).Central corneal thickness(CCT),anterior chamber depth(ACD),aqueous depth(AQD),white-to-white distance(WTW),flat simulated keratometry(Kf),steep simulated keratometry(Ks),mean keratometry(Km),and total corneal keratometry(TKm)were measured.Intraclass correlation coefficient(ICC),95%confidence intervals(CI)and limits of agreement(LoA)widths were conducted to assess differences and correlations between devices.RESULTS:All parameters,except for Ks,were significantly different.Pairwise comparison revealed no significant differences between keratometry obtained by IOLMaster 700 and Pentacam.LoA widths of all paired comparisons for Ks were>0.80 D.Except for WTW between IOLMaster 700 and CASIA2 and between CASIA2 and Pentacam,other Pearson’s coefficients between devices showed a strong correlation(all r>0.95).The ICC of WTW(ICC=0.438,95%CI 0.167-0.625)showed poor reliability.The reliability of CCT,ACD,and AQD was excellent(all ICC>0.95),whereas that of TKm was good(ICC=0.827,95%CI 0.221-0.939).A significant linear correlation was also observed among devices.CONCLUSION:The ocular parameters derived from the use of IOLMaster700,CASIA2,and Pentacam exhibit significant discrepancies;as such,measurements from these devices should not be deemed as interchangeable.

Pain perception enhancement in consecutive secondeye phacoemulsification cataract surgeries under topical anesthesia

Cataract is the main cause of visual impairment and blindness worldwide while the only effective cure for cataract is still surgery.Consecutive phacoemulsification under topical anesthesia has been the routine procedure for cataract surgery.However,patients often grumbled that they felt more painful during the second-eye surgery compared to the first-eye surgery.The intraoperative pain experience has negative influence on satisfaction and willingness for second-eye cataract surgery of patients with bilateral cataracts.Intraoperative ocular pain is a complicated process induced by the nociceptors activation in the peripheral nervous system.Immunological,neuropsychological,and pharmacological factors work together in the enhancement of intraoperative pain.Accumulating published literatures have focused on the pain enhancement during the secondeye phacoemulsification surgeries.In this review,we searched PubMed database for articles associated with pain perception differences between consecutive cataract surgeries published up to Feb.1,2024.We summarized the recent research progress in mechanisms and interventions for pain perception enhancement in consecutive secondeye phacoemulsification cataract surgeries.This review aimed to provide novel insights into strategies for improving patients’intraoperative experience in second-eye cataract surgeries.