NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

Sutured scleral fixation of existing subluxated/dislocated acrylic one-piece intraocular lenses

AIM:To evaluate the visual and refractive outcomes in cases after sutured scleral fixation of existing subluxated or dislocated acrylic one-piece intraocular lenses(IOLs).METHODS:This study retrospectively enrolled a consecutive series of patients who underwent a surgery of sutured existing subluxated or dislocated IOLs from October 2018 to June 2020.All patients underwent comprehensive preoperative and postoperative ophthalmologic examination,and data were collected including age,sex,surgical indications,best-corrected visual acuity,refractive error,intraocular pressure.Presence of intraoperative and postoperative surgical complications was documented.RESULTS:A total of 20 consecutive cases were enrolled for analysis with mean final follow-up period 9.8±5.3mo.Visual acuity improved from a mean of 0.35(0.46±0.32 logMAR)preoperatively to 0.61(0.21±0.18 logMAR)at the 3-month follow-up(P=0.002).The mean amount of preoperative keratometric astigmatism and total postoperative refractive astigmatism was-1.24±0.80 diopters(D)and-1.42±0.97 D,respectively.There was no statistically significant difference between preoperative and postoperative astigmatism(P=0.156).The mean IOL-induced astigmatism was-0.23±0.53 D.The mean spherical equivalent at the 3-month follow-up was-0.1±0.94 D.No major complications were noted during the follow-up period.CONCLUSION:Surgical techniques using sutured scleral fixation of existing subluxated or dislocated acrylic one-piece IOLs result in favorable visual and refractive outcomes without major complications.

Axial length,vitreoretinal pathology,and anterior chamber depth can predict postoperative refractive outcomes in phacovitrectomy/silicone oil removal

AIM:To evaluate the postoperative refractive prediction error(PE)and determine the factors that af fect the refractive outcomes of combined pars plana vitrectomy(PPV)or silicone oil removal(SOR)with cataract surgery.METHODS:The study is a retrospective,case-series study.Totally 301 eyes of 301 patients undergoing combined PPV/SOR with cataract surgery were enrolled.Eligible individuals were separated into four groups according to their preoperative diagnoses:silicone oil-filled eyes after PPV(group 1),epiretinal membrane(group 2),macular hole(group 3),and primary retinal detachment(RD;group 4).The variables af fecting postoperative refractive outcomes were analyzed,including age,gender,preoperative best-corrected visual acuity(BCVA),axial length(AL),keratometry average,anterior chamber depth(ACD),intraocular tamponade,and vitreoretinal pathology.The outcome measurements include the mean refractive PE and the proportions of eyes with a PE within±0.50 diopter(D)and±1.00 D.RESULTS:For all patients,the mean PE was-0.04±1.17 D,and 50.17%of patients(eyes)had a PE within±0.50 D.There was a significant difference in refractive outcomes among the four groups(P=0.028),with RD(group 4)showing the least favorable refractive outcome.In multivariate regression analysis,only AL,vitreoretinal pathology,and ACD were strongly associated with PE(all P<0.01).Univariate analysis revealed that longer eyes(AL>26 mm)and a deeper ACD were correlated with hyperopic PE,and shorter eyes(AL<26 mm)and a shallower ACD were correlated with myopic PE.CONCLUSION:RD patients have the least favorable refractive outcome.AL,vitreoretinal pathology,and ACD are strongly associated with PE in the combined surgery.These three factors affect refractive outcomes and thus can be used to predict a better postoperative refractive outcome in clinical practice.

Early clinical outcome with lens position adjustment following implantable collamer lens surgery

AIM:To observe early clinical outcome with lens position adjustment following the implantable collamer lens(ICL)surgery.METHODS:Sixty patients were selected for this retrospective study.One eye from each patient received Toric ICL for astigmatism correction,and the other received non-astigmatic ICL surgery using horizontal position.Patients with higher postoperative arch height were selected,and their non-astigmatic eye clinical outcome were observed after ICL surgery at 1wk,1,and 3mo.The clinical measurements included uncorrected visual acuity(UCVA),intraocular pressure(IOP),refractive state,corneal endothelium cell count,and arch height.Three months later,the ICL in each patient’s non-astigmatic eye was adjusted to the vertical from the horizontal position.The results were compared before and 1wk,1,and 3mo after adjustment.RESULTS:UCVA and IOP were significantly reduced 1wk after position adjustment compared to 1wk after ICL implantation(P<0.05).The patients demonstrated significantly reduced arch height and corneal endothelium cell count 1wk,1,and 3mo after adjusting position compared to 1wk,1,and 3mo after ICL implantation(P<0.05).However,there was no significant difference in refraction between 1wk,1,and 3mo after ICL implantation and position adjustment(P>0.05).CONCLUSION:Early positioning adjustment postphakic ICL implantation can benefit patients with adjusted arch height or higher IOP.Despite the good clinical effects,the doctors should pay attention to the potential for adverse effects on UCVA and corneal endothelium cells following early position adjustment after posterior chamber phakic ICL implantation.

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

Going straight for the gut:gut-brain axis pathology and treatment of Parkinson's disease

This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most common neurodegenerative disease in the United States,yet therapies remain limited.Current research suggests that the GBA may play a role in the pathogenesis of PD.GBAbased FMT as well as SCT offer promising new avenues for PD treatment.Pro bing the interactions between FMT and SCT with the GBA may reveal novel therapeutics for PD.

Evaluating the Effects of Graviton Redshift upon Spiral Galaxy Rotation Curves, Surface Brightness Magnitudes and Gravitational Lensing

The effects of the gravitational redshift of gravitons upon spiral galaxy rotation energy are compared to the standard mass to light analyses in obtaining rotation curves. The derivation of the total baryonic matter compares well with the standard theory and the rotation velocity is matched to a high precision. The stellar mass distributions obtained from the fit with graviton energy loss are used to derive the surface brightness magnitudes for the galaxies, which agree well with the observed measurements. In a new field of investigation, the graviton theory is applied to the observations of gravitational lenses. The results of these applications of the theory suggest that it can augment the standard methods and may eliminate the need for dark matter.

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

Hysterectomies for Gynaecological Pathology: 56 Cases at the Segou Regional Hospital in Mali

Introduction: Hysterectomy is a surgical procedure involving partial or total removal of the uterus. It is the most common gynaecological surgery in the world. Objective: To describe the epidemio-clinical and prognostic aspects of gynaecological hysterectomies. Patients and methods: This was an 18-month retrospective prospective descriptive study with a six-month follow-up period from 1 December 2020 to 31 May 2022 carried out in the gynaecology department of the Segou regional hospital. Results: Fifty-six (56) hysterectomies were performed out of 118 gynaecological surgical procedures (47.45%). The mean age was 47 ± 11.77 years. Large multiparous women were the most common (50%), with an average parity of 4.58. The main indications were uterine fibroids (30.4%), precancerous lesions of the cervix (17.85%) and uterine prolapse (17.85%). The abdominal route was the most commonly used surgical route (82.14%). Hysterectomy was total in 100% of cases and associated with bilateral adnexectomy in 48.2% of cases. The intra- and post-operative prognosis was satisfactory in 94.6% of cases. No deaths were recorded. The average length of stay was 3.28 days, irrespective of the surgical approach. Three cases of dyspareunia were noted among those who had resumed sexual activity.

Clinical prediction of insufficient vaults after implantable collamer lens implantation

AIM:To determine the factors related to preoperative ocular characters that are predictive of insufficient vault(<250μm)after implantable collamer lens(ICL V4c;STAAR Surgical)implantation.METHODS:The participants underwent ICL surgery and were divided into the low(<250μm)and normal(250-1000μm)vault groups based on the postoperative vault at 3mo.The preoperative biometric parameters and clinical outcomes were compared between the two groups.The relationship between the 3-month vault values and preoperative ocular parameters were evaluated by Generalized estimating equations.RESULTS:Sixteen(23 eyes)and 36 patients(63 eyes)were in the low and normal vault groups,respectively.All implantation procedures were uneventful with no cataract formation in the early postoperative period.The sulcusto-sulcus lens rise(STSL)and iris ciliary angle(ICA)were correlated with vault at 3mo after surgery.Every 0.1 mm increase in STSL was associated with 38.9μm decrease in the postoperative 3-month vault.A rise of 1 degree in ICA is associated with a reduction of 4μm in vault.CONCLUSION:Eyes with a narrow ciliary sulcus are associated with a higher rate of low vault after ICL implantation,suggesting a need for adjustments to the ICL size in these patients.Evaluating the characteristics of the ciliary sulcus contributes valuable information to predict low vault after surgery.

Intraocular lens selection in diabetic patients:How to increase the odds for success

The incidence of cataracts is significantly higher in diabetic individuals,particularly in younger age groups,with rates quadrupled in those under 65 and doubled in those over 65 compared to non-diabetics.Cataract surgery in diabetic patients poses many challenges:Poor epithelial healing,decreased corneal sensitivity,increased central corneal thickness,decreased endothelial cell count,variable topography,poor pupillary dilatation,anterior capsular phimosis,posterior capsular opacification(PCO),chances of progression of diabetic retinopathy(DR),zonular weakness,and vitreous prolapse and diabetic macular edema.Selection of an appropriate intraocular lens(IOL)is crucial for visual rehabilitation and monitoring DR.The choice of IOL in diabetic cataract patients is a challenging scenario.Square-edge IOLs are favored for their capacity to mitigate PCO,whereas hydrophilic counterparts may incur calcification in the setting of proliferative DR.The advisability of premium IOLs for achieving spectacle independence warrants judicious evaluation,particularly in the presence of advanced retinopathy.Optimal IOL placement within the capsular bag is advocated to minimize postoperative complications.Rigorous preoperative assessment and informed patient counseling regarding IOL options are indispensable for optimizing surgical outcomes.This review article covers various aspects regarding the choice of IOLs in different case scenarios and complications in the diabetic population.

Prevalence of retinal pathologies in people over 60 years:the Tehran Geriatrics Eye Study

AIM:To determine the prevalence of some retinal pathologies in people over 60y and their association with demographic and ocular factors.METHODS:A cross-sectional study was conducted in Tehran using multistage cluster sampling.After selecting subjects aged 60 and over,optometric,and ophthalmic examinations were done.For retinal examination,a 90 D lens was used and indirect ophthalmoscopy was performed after instilling tropicamide drops.Biometry was done using the IOL Master for all participants.RESULTS:Of 3791 people that were invited through cluster sampling,3310 participated in the study(response rate=82%).The prevalence of retinal pigmented epithelium(RPE)change,drusen,geographic atrophy(GA),hypertensive retinopathy(HTR),nonproliferative diabetic retinopathy(NPDR),proliferative diabetic retinopathy(PDR),choroidal neovascularization(CNV),central retinal artery occlusion(CRAO),myopic retinopathy(MR),branch retinal vein occlusion(BRVO),and central retinal vein occlusion(CRVO)was 27.42%,11.08%,4.52%,3.03%,4.05%,0.54%,0.82%,0.39%,0.20%,0.49%,and 0.19%,respectively.After removing the effect of age,the odds of NPDR were 1.68 times higher in women compared to men(P=0.014).After removing the effect of sex,the odds of drusen,RPE change,GA,CNV,BRVO,and CRVO increased with age.CONCLUSION:There is a higher prevalence of RPE change,drusen,GA,CNV and a lower prevalence of MR and CRAO in the elderly population of Tehran aged over 60y compared to global average values.Considering the correlation of most of the diseases with age and their effects on vision,attention should be paid to these diseases and the related screening programs to prevent vision impairment.

Impact of multifocal gas-permeable lens designs on short-term choroidal response, axial length, and retinal defocus profile

AIM:To investigate the impact of multifocal gas permeable contact lens(MFGPCL)in various add power and distance/near area allocation on short-term changes of choroidal thickness(ChT),axial length(AL),and retinal defocus profile in young adults.METHODS:Seventeen young adults(2 males and 15 females;age 23.17±4.48y)were randomly assigned to wear two designs binocularly with a one-week washout period in between.Total of four MFGPCL designs were assessed.All designs were distance-center that varied in two add power(+1.50 and 3.00 D)and/or two distance zone(DZ)diameters(1.50 and 3.00 mm;design A:DZ 1.5/add 3.0,B:DZ 1.5/add 1.5,C:DZ 3.0/add 3.0,D:DZ 3.0/add 1.5).ChT,AL,and peripheral refraction data were collected on each subject at baseline,on days 1 and 7 of MFGPCL daily wear.ChT was assessed in four quadrants using a spectraldomain optical coherence tomography.RESULTS:AL was shortened by-26±44μm with lens C,-18±27μm with lens D,-13±29μm with lens A,and-8±30μm with lens B(all P<0.05).A significant overall increase in ChT was observed with all 4 designs(lens A:+6±6μm,B:+3±7μm,C:+8±7μm,and D:+8±7μm).Temporal and superior choroid exhibited more choroidal thickening associated with MFGPCL.All designs induced significant relative peripheral myopia(RPM)beyond the central 20o across the horizontal meridian in both nasal and temporal fields(P<0.05).CONCLUSION:MFGPCLs show a significant influence on ChT and AL,which are associated with significant increase in RPM after short-term wear.The reliability and feasibility of quantifying short-term changes in ChT support its use as a promising marker for the long-term efficacy of myopia-controlling treatments.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract:a randomized clinical trial

●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.

Rhegmatogenous retinal detachment in highly myopic eyes with implantable collamer lens

AIM:To investigate the clinical characteristics,treatment methods and outcomes of rhegmatogenous retinal detachment(RRD)in highly myopic eyes with implantable collamer lens(ICL).METHODS:High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were reviewed.Comprehensive ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each patient.RESULTS:A total of nine RRD eyes from nine patients who received V4c-ICL implantation were included.The mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo(range,1-60mo).At the initial visit for RRD,giant retinal tear(GRT),horseshoe tear,simple round hole,and horseshoe tear combined with round hole were detected in 3,3,2,and 1 eye(s),respectively,with maculaoff in eyes.Eight patients received surgical treatment,and one patient was treated by retinal laser photocoagulation alone.The ICL was preserved in 7 eyes.At the last followup,the mean best corrected visual acuity(BCVA)improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR(P=0.035),and no case of recurrent retinal detachment was found.CONCLUSION:The morphological presentation of retinal breaks is diverse in this study.The ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data,companied with acceptable visual and anatomical outcomes.

Covering corneal stromal lenticule for macular hole in pathological myopia

AIM:To evaluate the clinical effect of a new surgery technique(covering corneal stromal lenticule,CSL)for macular hole(MH)in pathological myopia.METHODS:This was a prospective non-randomized series case study.Fourteen eyes of 14 patients whose axial length were more than 29 mm and suffered from MH and macular hole retinal detachment(MHRD)were included in this study.All cases were treated with 25-gauge pars plana vitrectomy(PPV)with internal limiting membrane(ILM)peeling,covering CSL and C_(3)F_(8) gas tamponade.These cases were followed for 6mo,and the best-corrected visual acuity(BCVA),healing status of MH,the reattached rate of retinal detachment(RD),and reoperation rate were analyzed.RESULTS:All cases were successfully performed the surgery and the postoperative follow-up was completed.After surgery,MHs were healed in all 14 eyes(100%,14/14)after assessed by optical coherence tomography.The reattachment of retina was achieved in all 6 eyes(100%,6/6)with MHRD.BCVA was improved in 12 eyes(85.71%,12/14),and had no significant change in 2 eyes(14.29%,2/14).The overall mean BCVA was improved from 1.80±0.77 to 0.82±0.46 logMAR(F=10.46,P<0.01).No serious complications occurred in all cases.CONCLUSION:The new surgery technique(covering CSL)has high reattached rate of RD and high healing rate of MH in pathological myopia in the preliminary study.And it can effectively improve the visual function of patients.This new technique offers meaningful new ideas for treating refractory MH in pathological myopia.

Design and fabrication of compound varifocal lens driven by polydimethylsiloxane film elastic deformation

A compound varifocal lens based on electromagnetic drive technology is designed and fabricated, where the polydimethylsiloxane(PDMS) film acts as a driving component, while the PDMS biconvex lens and the plane-concave lens form a coaxial compound lens system. The plane-concave lens equipped with driving coils is installed directly above the PDMS lens surrounded by the annular magnet. When different currents are applied, the annular magnet moves up and down, driving the PDMS film to undergo elastic deformation, and then resulting in longitudinal movement of the PDMS lens. The position change of the PDMS lens changes the focal length of the compound lens system. To verify the feasibility and practicability of this design, a prototype of our compound lens system is fabricated in experiment. Our proposed compound lens shows that its zoom ability reaches 9.28 mm when the current ranges from -0.20 A to 0.21 A.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca^(2+)-dependent AMPK/mTOR pathway

●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

Refractive outcomes after V4c Toric collamer lens implantation over 1y of follow-up

AIM:To evaluate refractive outcomes and corneal astigmatism changes after Toric implantable collamer lens with a central port(V4c T-ICL)implantation over 1y of follow-up.METHODS:A retrospective study was performed including 50 eyes of 50 patients that underwent V4c T-ICL implantation.Uncorrected(UDVA)and corrected(CDVA)distance visual acuities,refraction,refractive and corneal astigmatism changes and corneal coupling correction were evaluated preoperatively,1 and 12mo postoperatively.Vector analysis was used for astigmatism changes.Coefficient of adjustment(CAdj)was calculated for corneal coupling analysis.RESULTS:The mean UDVA achieved was 0.03 logMAR at 1mo and remained unchanged throughout the whole follow-up(P=0.193).At the last visit,84%of the eyes achieved a CDVA of 0.00 logMAR or better.Regarding spherical equivalent refraction(SEQ),96%of eyes were ranges of±1.00 D and 84%of them within±0.50 D.Also,94%of eyes had a remaining refractive cylinder within±1.00 D and 78%of them within±0.50 D.Both,SEQ and refractive cylinder,remain stable over the postoperative follow-up(P=1.000 and P=0.660,respectively).In terms of surgically induced astigmatism(SIA),no statistically significant differences were found over the follow-up(P=0.102)and under correction was found with a correction index lower than the unit at each visit.A keratometric astigmatism induced of 0.59±0.53(vector mean:0.26×73º)D was reached at the last visit.No significant changes in terms of corneal astigmatism orientation were reported over post-surgery visits(P=0.129 and P=0.097 at 1 and 12mo respectively).No clinical significance was found for CAdj on with-the-rule astigmatism.No postoperative complications resulting from the surgery were found.CONCLUSION:Refractive outcomes suggest that the V4c T-ICL implantation for correction of myopic astigmatism was satisfactory in terms of effectiveness,safety,and stability during 1y of follow-up.Corneal astigmatism induced by the incision around 0.5 D is achieved according to the remaining refractive cylinder found at one-year post-surgery.Corneal coupling analysis results in no unexpected spherical change.