Targeting Nrf2 signaling in dry eye

Dry eye,the most common ocular surface disease,can cause ocular surface tissue damage and discomfort symptoms and seriously affect people’s quality of life.The etiology of dry eye is diverse,and its pathogenesis is complex.The oxidative stress reaction is considered to be among the important factors in the pathogenesis of dry eye.Therefore,activating the antioxidant system has a potential therapeutic effect on dry eye.Nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway is considered the most important antioxidant pathway in the body.The activation of the Nrf2 signaling pathway and its interaction with other pathways are important mechanisms to prevent the occurrence and development of dry eye.This review describes the structure and function of Nrf2,summarizes the changes in the oxidative stress response in dry eye,focuses on the potential mechanism of the Nrf2 signaling pathway in the treatment of dry eye,and,finally,summarizes the drugs that activate the Nrf2 signaling pathway in the treatment of dry eye.

Psychometric validation of the Chinese version of the dry eye-related quality-of-life score questionnaire

AIM:To psychometrically validate the Chinese version of the dry eye-related quality-of-life score questionnaire(DEQSCHN)among Chinese patients with dry eye.METHODS:This study involved 231 participants,including 191 with dry eye disease(DED)comprising the dry eye disease group,and 40 healthy participants forming the control group.Participants were required to complete the DEQS-CHN,and Chinese dry eye questionnaire and undergo clinical tests including the fluorescein breakup time(FBUT),corneal fluorescein staining(CFS),and Schirmer I test.To assess the internal consistency and retest reliability,Cronbach’sαand the intraclass correlation coefficient(ICC)were employed.Content validity was assessed by item-level content validity index(ICV)and an average scale-level content validity index(S-CVI/Ave).Construct validity was assessed by confirmatory factor analysis.The concurrent validity was assessed by calculating correlations between DEQS-CHN and Chinese dry eye questionnaire.Discriminative validity was evaluated through nonparametric tests,with receiver operating characteristic(ROC)curve serving as conclusive indicators of the questionnaire’s distinguishing capability.RESULTS:The Cronbach’sαcoefficients for frequency and degree of ocular symptoms,impact on daily life,and summary score were 0.736,0.704,0.811,0.818,0.861,and 0.860,respectively,and the ICC were 0.611,0.677,0.715,0.769,0.711,and 0.779,respectively.All I-CVI scores ranged from 0.833 to 1.000,with an S-CVI/Ave of 0.956.Confirmatory factor analysis results exhibited a wellfitting model consistent with the original questionnaire[χ^(2)/df=2.653,incremental fit index(IFI)=0.924,comparative fit index(CFI)=0.924,Tucker-Lewis index(TLI)=0.909,and root mean square error of approximation(RMSEA)=0.065].There was a moderate positive correlation between the DEQS-CHN and the Chinese dry eye questionnaire(r^(2)=0.588).The dry eye group demonstrated significantly higher scores compared to the control group,and the area under the curve(AUC)value was 0.8092.CONCLUSION:The DEQS-CHN has been demonstrated as a valid and reliable instrument for assessing the impact of dry eye disease on the quality of life among Chinese individuals with DED.

A Rational Design of Metal–Organic Framework Nanozyme with High‑Performance Copper Active Centers for Alleviating Chemical Corneal Burns

Metal–organic frameworks(MOFs)have attracted significant research interest in biomimetic catalysis.However,the modulation of the activity of MOFs by precisely tuning the coordination of metal nodes is still a significant challenge.Inspired by metalloenzymes with well-defined coordination structures,a series of MOFs containing halogen-coordinated copper nodes(Cu-X MOFs,X=Cl,Br,I)are employed to elucidate their structure–activity relationship.Intriguingly,experimental and theoretical results strongly support that precisely tuning the coordination of halogen atoms directly regulates the enzyme-like activities of Cu-X MOFs by influencing the spatial configuration and electronic structure of the Cu active center.The optimal Cu–Cl MOF exhibits excellent superoxide dismutase-like activity with a specific activity one order of magnitude higher than the reported Cu-based nanozymes.More importantly,by performing enzyme-mimicking catalysis,the Cu–Cl MOF nanozyme can significantly scavenge reactive oxygen species and alleviate oxidative stress,thus effectively relieving ocular chemical burns.Mechanistically,the antioxidant and antiapoptotic properties of Cu–Cl MOF are achieved by regulating the NRF2 and JNK or P38 MAPK pathways.Our work provides a novel way to refine MOF nanozymes by directly engineering the coordination microenvironment and,more significantly,demonstrating their potential therapeutic effect in ophthalmic disease.

Inflammatory Mechanism of Total Flavonoids of Chrysanthemum and Medicated Serum on Castrated Dry Eye Animal and Cell Models

Objective To observe the effects of total flavonoids of chrysanthemum and medicated serum on the expression of related proteins in the lacrimal tissue and dry-eye cell models of male rabbits with dry eye caused by castration.Methods(1)150 male Japanese rabbits were randomly divided into five groups,with 30 rabbits in each group:normal control group(group A),sham group(group B),model group(group C),androgen control group(group D)and total flavonoids of chrysanthemum treatment group(group E).The androgen deficiency dry-eye model was established by bilateral castration in groups C,D and E.Normal saline was administered to groups A,B and C by gavage;androgen(testosterone propionate)was injected into muscle in group D;and group E was given total flavonoids of chrysanthemum by gavage.All white rabbits were tested the Schirmer I test(SIT)and tear break-up time(BUT).After euthanasia,tear gland tissue was harvested so that we could observe pathological changes in the expression of related inflammatory factors in the lacrimal gland tissue.The expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and transforming growth factor-β1(TGF-β1)was detected in the lacrimal gland tissue by immunohistochemistry.Reverse transcription PCR was used to quantitatively detect expression of TGF-β1 mRNA.(2)Male Wistar rat lacrimal epithelial cells were used to establish a model of eye stem cell apoptosis caused by androgen levels.The blank control group was set up without androgen culture,the control group with androgen culture,and the total flavonoids of chrysanthemum group without androgen.The MTT method was used to determine the optimal intervention dosage of drug-containing plasma.Western blot and QPCR were used to detect the expression of AR mRNA,NF-κB phosphorylated protein and TGF-β1 in lacrimal epithelial cells,and the androgen-like effect of total flavonoids of chrysanthemum was observed.Results(1)Immunohistochemistry showed that groups A,B,D and E had significantly lower expression of IL-1βand TNF-αthan group C(P<0.05);among these,group E had slightly higher expression than group D(P>0.05).RT-PCR results showed that the relative expression of TGF-β1 mRNA in groups A,B,D and E was significantly higher than in group C(P<0.05),and the relative expression of TGF-β1 mRNA in groups D and E was higher than that in groups A and B(P<0.05).(2)Using the MTT method,the final concentration of interfering cells was calculated to be 13.2%.The expression of AR protein,NF-κB and TGF-β1 in the chrysanthemum flavonoid plasma intervention and testosterone propionate intervention groups was enhanced,and there were significant differences relative to the blank group(P<0.01).The expression level of NF-κB in the total flavonoid containing plasma intervention group was lower than that in the testosterone propionate intervention group(P<0.01).Conclusions The total flavonoids of chrysanthemum can inhibit IL-1βand TNF-αexpression in the lacrimal gland tissue of castrated male rabbits with dry eye to increase synthesis of TGF-β1 mRNA and TGF-β1,thereby inhibiting the inflammatory response.The medicated plasma with total flavonoids of chrysanthemum promotes expression of AR mRNA,upregulating expression of NF-κB,further promoting upregulation of TGF-β1 protein expression in lacrimal epithelial cells,inhibiting inflammation by regulating related proteins,and ultimately alleviating the symptoms of dry eye.

Visual acuity of urban and rural adults in a coastal province of southern China:the Fujian Eye Study

AIM:To evaluate the vision status and sociodemographic associations of visual acuity(VA)in an urban and rural population in a coastal province of southern China.METHODS:The Fujian Eye Study,a population-based cross-sectional study,was performed from May 2018 to October 2019.Totally 10044 participants over 50 years old from all nine cities in Fujian Province were enrolled,and underwent a questionnaire and a series of standard physical and ocular examinations.VA was measured by E Standard Logarithmic Visual Acuity Chart(GB 11533-1989).Data was double entered with Epi Data v3.1 for data collation and Stata/SE statistical software v15.1 was used to analyze the data.RESULTS:Totally 8211(81.8%)participants were finally included and were divided into urban populations(4678 subjects),rural populations(n=3533),coastal residents(n=6434),and inland residents(1777 subjects);4836 participants were female.The mean age was 64.39±8.87 y(median 64 y;range 50-98 y).The mean presenting VA was 0.61±0.30(0.23±0.27 log MAR),and the mean best correctedvisual acuity(BCVA)was 0.82±0.28(0.08±0.19 log MAR).In the multiple regression analysis,BCVA was significantly correlated with several socioeconomic and biologic factors,including age(P<0.001),education level(P<0.001),income(P=0.005),rural residency(P<0.001),inland residency(P=0.001)and refractive error(P<0.001),while sex(P=0.194)was independent with BCVA.CONCLUSION:Accessible services and eye health policies targeting the elderly,people with high myopia and people living in rural or inland areas are needed.

Topical tear stimulation-a new insight for dry eye therapy

Dry eye disease is the most prevalent ocular surface disease in eye clinics.The deficiency of tears is regarded as one of the main pathogenic factors for this disease.Due to the fact that the components of tears are still far beyond our knowledge,the restoration of physiological tears remains the optimum choice for dry eye patients.However,the traditional way to stimulate tear production by systemic administration of muscarinic agonists usually encounters severe side effects.Recently,Nakamachi and colleagues reported that PACAP,a native neurotransmitter present in tear fluid,could stimulate main lacrimal gland secretion and relieve dry eye-like symptoms in PACAP knockout mice.The finding of PACAP and its underlying mechanisms suggest a new modality for dry eye treatment via targeted topical tear stimulations.

Safety profile of 0.0015%tafluprost eye drops in China:a post-marketing observational study

AIM:To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension(OH)in clinical practice in China.METHODS:This post-marketing observational study included patients who received tafluprost to lower intraocular pressure(IOP)within 30d between September 2017 and March 2020 in 20 hospitals in China.Adverse drug reactions(ADRs)during tafluprost treatment and within 30d after the treatment were collected.RESULTS:A total of 2544 patients were included in this study,of them 58.5%(1488/2544)had primary open angle glaucoma(POAG),21.9%(556/2544)had OH and 19.7%(500/2544)used tafluprost for other reasons.Of 359 ADRs occurred in 10.1%(258/2544)patients,and no serious adverse event occurred.The most common ADR was conjunctival hyperemia(128 ADRs in 124 patients,4.9%).Totally 1670 participants(65.6%)combined tafluprost with carbonic anhydrase inhibitors(CAIs;37.1%,620/1670),sympathomimetics(33.5%,559/1670),β-blockers(33.2%,555/1670),other prostaglandin analogs(PGAs;15.6%,260/1670)and other eye drops(15.1%,253/1670).The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs(23 ADRs in 23 patients,8.8%,23/260)and the lowest was in combination with CAIs(16 ADRs in 16 patients,2.6%,16/620).Tafluprost was applied in primary angle-closure glaucoma(41.6%,208/500),after glaucoma surgery(17.8%,89/500)and after non-glaucoma surgery(15.8%,79/500).CONCLUSION:Tafluprost is safe for POAG and OH,and tolerable when combined with other eye drops and under various clinical circumstances.

Hydromassage of macular hole edges for large and persistent full-thickness macular holes

●AIM:To introduce the macular hole(MH)hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH.●METHODS:This retrospective observational case series comprised 16 consecutive patients(17 eyes)diagnosed with MH.Inclusion criteria involved a hole aperture diameter larger than 600μm or the presence of an unclosed MH larger than 600μm following the previous vitrectomy.Standard MH repair procedures were administered in all cases,involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle.A comprehensive assessment was conducted for each case before and after surgery,and optical coherence tomography(OCT)images were captured at every follow-up point.●RESULTS:The mean preoperative aperture diameter was 747±156μm(range 611-1180μm),with a mean base diameter of 1390±435μm(range 578-2220μm).Following surgery,all cases achieved complete anatomical closure of MH,with 13 cases(76.5%)exhibiting type 1 closure and 4 cases(23.5%)demonstrating type 2 closure.No significant differences were observed in the preoperative OCT variables between the two closure types.Eyes with type 1 closure showed a significantly improved visual acuity(0.70±0.10,range 0.50-0.80)compared to those with type 2 closure(0.90±0.12,range 0.80-1.00,P=0.014).●CONCLUSION:The MH hydromassage technique demonstrates promising results,achieving acceptable closure rates in cases of large or persistent MH.This technique may serve as an effective adjunctive maneuver during challenging MH surgery.

Exploring the Impact of Alcohol Consumption and Smoking on Primary Open Angle Glaucoma: A Mendelian Randomization Study

Objective: Utilizing Mendelian Randomization, this study employs Single Nucleotide Polymorphisms (SNPs) as instrumental variables to explore the causal relationships between bibulosity, smoking, and Primary Open Angle Glaucoma (POAG). Methods: GWAS data for bibulosity, smoking, and POAG were obtained from the Social Science Genetic Association Consortium website and the IEU OpenGWAS Project website, respectively. Using a P-value threshold of −8, a linkage disequilibrium coefficient (r2) of 0.001, and a linkage disequilibrium region width of 10,000 kb, the data were aggregated, resulting in 6 SNPs for bibulosity and 253 SNPs for smoking. Three regression models, MR-Egger, Weighted Median Estimator (WME), and Random-Effects Inverse-Variance Weighted (IVW) were applied to analyze the causal impact of bibulosity and smoking on POAG. Results: The GWAS data for alcohol consumption and smoking were derived from European populations, while the GWAS data for Primary Open-Angle Glaucoma (POAG) were sourced from East Asian populations, with no gender restrictions. Analysis using three different regression models revealed that neither excessive alcohol consumption nor smoking significantly increased the risk of developing POAG. Specifically, the odds ratios with 95% confidence intervals for the alcohol consumption group were 0.854 (0.597 - 1.221) in MR-Egger regression, 0.922 (0.691 - 1.231) in WME regression, and 0.944 (0.711 - 1.252) in IVW regression. For the smoking group, the odds ratios were 1.146 (0.546 - 2.406) in MR-Egger regression, 0.850 (0.653 - 1.111) in WME regression, and 0.939 (0.780 - 1.131) in IVW regression. Given the significant heterogeneity in the SNPs associated with smoking, the focus was primarily on the results from the IVW regression model. Conclusion: Alcohol consumption and smoking are not significant risk factors for the development of POAG.

Revamping anti-cGAS-STING therapy via an injectable thermo-responsive supramolecular hydrogel for pathological retinal angiogenesis

Retinal neovascularization is a leading cause of blindness.While current anti-VEGF drugs effectively inhibit pathological angiogenesis,some patients develop resistance or reduced responsiveness to treatments over time,leading to diminished effectiveness.In this study,we identified high activation of the cGAS-STING signaling pathway,which exacerbated pathological neovascularization and vessel leakage.We developed an injectable thermo-responsive supramolecular hydrogel loaded with an anti-STING drug.The hydrogel,made of Pluronic F127 demonstrated excellent transparency and biocompatibility.Importantly,the thermo-sensitive property allowed for precise spatial release of the drug,extending the effective treatment duration of C-176,which suppressed STING activation in the retina,reduced inflammation and protected retinal tissue.Hydro^(C-176) effectively inhibited microglial cell infiltration and the release of inflammatory angiogenic factors,highlighting its enhanced efficacy.While demonstrating slightly lower effectiveness compared to traditional anti-VEGF therapy,Hydro^(C-176) exhibited more robust capabilities in regulating ocular microenvironmental inflammation.This approach may assist in enhancing the sensitivity and effectiveness of anti-VEGF therapy for reducing ocular inflammation,potentially improving patients’response to traditional treatment.These results have suggested innovative and comprehensive strategies for the management of retinal neovascularization.

Alkali burn injury model of meibomian gland dysfunction in mice

AIM:To establish a stable,short-time,low-cost and reliable murine model of meibomian gland dysfunction(MGD).METHODS:A filter paper sheet soaked in 1.0 mol/L sodium hydroxide(NaOH)solution was used to touch the eyelid margin of C57BL/6J mice for 10s to establish the model.The other eye was left untreated as a control group.Eyelid margin morphological changes and the meibomian glands(MGs)were observed by slit lamp microscopy on days 5 and 10 post-burn.Hematoxylin-eosin(HE)staining and Oil red O staining were adopted in detecting the changes in MGs morphology and lipid deposition.Real-time polymerase chain reaction,Western blot,immunofluorescence staining and immunohistochemical staining were used to detect interleukin(IL)-6,IL-1β,IL-18,tumor necroses factor(TNF)-α,interferon(IFN)-γ,nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4),3-nitroturosine(3-NT),4-hydroxynonenal(4-HNE)and cytokeratin 10(K10)expression changes in MGs.RESULTS:MGs showed plugging of orifice,glandular deficiency,abnormal acinar morphology,ductal dilatation,and lipid deposition after alkali burn.The expressions of IL-6,IL-18,IL-1β,IFN-γ,and TNF-αindicators of inflammation and oxidative stress in MGs tissues were significantly increased.Abnormal keratinization increased in the MG duct.CONCLUSION:A murine model of MGD is established by alkali burn of the eyelid margin that matches the clinical presentation of MGD providing a stable,short-time,lowcost,and reliable MGD model.The new method suggests efficient avenues for future research.

Optical quality of toric intraocular lens implantation in cataract surgery

AIM: To analyze the optical quality after implantation of toric intraocular lens with optical quality analysis system.METHODS: Fifty-two eyes of forty-four patients with regular corneal astigmatism of at least 1.00 D underwent implantation of Acry Sof toric intraocular lens, including T3 group 19 eyes, T4 group 18 eyes, T5 group 10 eyes,T6 group 5 eyes. Main outcomes evaluated at 3mo of follow-up, included uncorrected distance visual acuity(UDVA), corrected distance visual acuity(CDVA), residual refractive cylinder and intraocular lens(IOL) axis rotation.Objective optical quality were measured using optical quality analysis system(OQAS Ⅱ, Visiometrics, Spain),included the cutoff frequency of modulation transfer function(MTFcutoff), objective scattering index(OSI),Strehl ratio, optical quality analysis system value(OV)100%, OV 20% and OV 9% [the optical quality analysis system(OQAS) values at contrasts of 100%, 20%, and 9%].RESULTS: At 3mo postoperative, the mean UDVA and CDVA was 0.18 ±0.11 and 0.07 ±0.08 log MAR; the mean residual refractive cylinder was 0.50 ±0.29 D; the mean toric IOL axis rotation was 3.62 ±1.76 degrees, the mean MTFcutoff, OSI, Strehl ratio, OV 100%, OV 20% and OV9% were 22.862 ±5.584, 1.80 ±0.84, 0.155 ±0.038, 0.76 ±0.18,0.77±0.19 and 0.78±0.21. The values of UDVA, CDVA, IOL axis rotation, MTFcutoff, OSI, Strehl ratio, OV100%,OV20% and OV9% depending on the power of the cylinder of the implantation were not significantly different(P 】0.05), except the residual refractive cylinder(P 【0.05).CONCLUSION: The optical quality analysis system was useful for characterizing the optical quality of Acry Sof toric IOL implantation. Implantation of an Acry Sof toric IOL is an effective and safe method to correct corneal astigmatism during cataract surgery.

Oxidative stress affects retinal pigment epithelial cell survival through epidermal growth factor receptor/AKT signaling pathway

AIM：To investigate the cross-talk between oxidative stress and the epidermal growth factor receptor（EGFR）/AKT signaling pathway in retinal pigment epithelial（ RPE） cells.METHODS：Human RPE cell lines（ARPE-19 cell） were treated with different doses of epidermal growth factor（EGF） and hydrogen peroxide（H2O2）.Cell viability was determined by a methyl thiazolyl tetrazolium assay.Cell proliferation was examined by a bromodeoxyuridine（Brd U） incorporation assay.EGFR/AKT signaling was detected by Western blot.EGFR localization was also detected by immunofluorescence.In addition,EGFR/AKT signaling was intervened upon by EGFR inhibitor（erlotinib）,PI3 K inhibitor（A66） and AKT inhibitor（MK-2206）,respectively.H2O2-induced oxidative stress was blocked by antioxidant N-acetylcysteine（NAC）.RESULTS：EGF treatment increased ARPE-19 cell viabili ty and proliferation through inducing phosphorylation of EGFR and AKT.H2O2 inhibited ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated increase of RPE cell viability and proliferation by affecting the EGFR/AKT signaling pathway.EGFR inhibitor erlotinib blocked EGF-induced phosphorylation of EGFR and AKT,while A66 and MK-2206 only blocked EGF-induced phosphorylation of AKT.EGF-induced phosphorylation andendocytosis of EGFR were also affected by H2O2 treatment.In addition,antioxidant NAC attenuated H2O2-induced inhibition of ARPE-19 cell viability through all eviating reduction of EGFR,and phosphorylated and total AKT proteins.CONCLUSION：Oxidative stress affects RPE cell viability and proliferation through interfering with the EGFR/AKT signaling pathway.The EGFR/AKT signaling pathway may be an important target in oxidative stress-induced RPE cell dysfunction.

Clinical analysis of tear film after lamellar keratoplasty

AIM: To study the tear film stability after lamellar keratoplasty METHODS: Five female and eight male patients with lamellar keratoconus, aged from 18 to 32, were involved. After lamellar keratoplasty, Schirmer I test (S I t), tear break-up time (BUT) test, fluorescein staining test were used to judge the effect of the surgery at different time point. RESULTS: The S 1 t were greatly increased in 7 clays post operation (11.86+/-2.28 -25.14+/-1.97, 19.86+/-1.61) (P<0.05), there is no significant difference between 2nd month, 3rd month post-operative and pre-operation(11.86+/- 2.28 - 14.57+/-1.48, 8.14+/-0.86) (P >0.05). The mean break-up time decreased in 7 days post operation (5.00+/-1.31 -2.71+/- 0.18, 2.57+/- 0.20, 2.71+/- 0.36, 2.43+/- 0.20) (P <0.05). The mean scores of fluorescence increased post-operatively (0.14+/- 0.14 - 8.00+/- 0.00, 8.00+/- 0.00, 8.00+/- 0.00, 7.57+/- 0.20) (P<0.01). CONCLUSION: Lamellar keratoplaty influence the tear film stability, artificial tears and improving corneal epithelium cured medicine should be used after surgery.

Altered spontaneous brain activity patterns in patients with diabetic retinopathy using amplitude of low-frequency fluctuation

BACKGROUND Diabetes mellitus is a metabolic disorder characterized by prolonged elevation of blood glucose due to various causes.Currently,the relationship between diabetic retinopathy(DR)and altered connectivity of brain function is unclear.AIM To investigate the relationship between this brain activity and clinical manifestations and behaviors of DR patients by using the amplitude of low-frequency fluctuation(ALFF)technique.METHODS Twenty-four DR patients and 24 healthy controls(HCs)matched for age and gender were enrolled.We measured and recorded average ALFF values of DR patients and HCs and then classified them using receiver operating characteristic(ROC)curves.RESULTS ALFF values of both left and right posterior cerebellar lobe and right anterior cingulate gyrus were remarkably higher in the DR patients than in the HCs;however,DR patients had lower values in the bilateral calcarine area.ROC curve analysis of different brain regions demonstrated high accuracy in the area under the curve analysis.There was no significant relationship between mean ALFF values for different regions and clinical presentations in DR patients.Neuronal synchronization abnormalities in some brain regions of DR patients were associated with cognitive and visual disorders.CONCLUSION Abnormal spontaneous brain activity was observed in many areas of DR patients’brains,which may suggest a possible link between clinical manifestations and behaviors in DR patients.

Neuroprotective effect of mesenchymal stem cellderived extracellular vesicles on optic nerve injury in chronic ocular hypertension

Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors,and which may be mediated by extracellular vesicles(or exosomes)released by mesenchymal stem cells.To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma,we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma.One week after injury,extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity.We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage,increased the number of retinal ganglion cells,and inhibited the activation of caspase-3.These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension,and this effect is achieved by inhibiting cell apoptosis.

A mutated CRYGD associated with congenital coralliform cataracts in two Chinese pedigrees

AIM:To investigate the causal gene mutation and clinical characteristics for two Chinese families with autosomal dominant congenital coralliform cataract.METHODS:Two Chinese pedigrees with congenital cataract were investigated.Routine ophthalmic examinations were performed on all patients and non-affected family members.Peripheral blood samples were collected,and the genomic DNAs were extracted.The coding regions of proband’s DNAs were analyzed with cataract gene panel.The identified mutation was amplified by polymerase chain reaction,and automated sequencing was performed in other members of two families to verify whether the mutated gene was co-segregated with the disease.RESULTS:Congenital coralliform cataract was inherited in an autosomal dominant mode in both pedigrees.For each family,more than half of the family members were affected.All patients presented with severe visual impairment after birth as a result of bilateral symmetric coralliform lens opacification.An exact the same defect in the same gene,a heterozygous mutation of c.70 C>A(p.P24 T)in exon 2 of γ Dcrystallin gene,was detected in both probands from each family.Sanger sequencing analysis demonstrated that the mutated CRYGD was co-segregated in these two families.CONCLUSION:A c.70 C>A(p.P24 T)variant in CRYGD gene was reconfirmed to be the causal gene in two Chinese pedigrees.It is known that mutated CRYGD caused most of the congenital coralliform cataracts,suggesting that the CRYGD gene is associated with coralliform congenital cataract.

Triamcinolone as an adjunct to the combination of anti-VEGF for the management of diabetic macular edema

AIM:To assess the efficacy of intravitreal triamcinolone(IVTA)as an adjunct to the combination of anti-vascular endothelial growth factor(VEGF)for the management of diabetic macular edema(DME).METHODS:A total of 51 patients with visual disabilities causing by DME from two sites were retrospectively collected and assigned to two groups according to the therapeutic method:intravitreal conbercept(IVC)combined with focal laser(24 eyes)and IVC combined with focal laser and IVTA(27 eyes).Best-corrected visual acuity(BCVA),the required number of IVCs,central retinal thickness(CRT),the mean costs of treatment burden and safety were compared over 12 mo.RESULTS:From baseline to month 1 through month 12,IVC combined with focal laser and IVTA improved the mean average change in BCVA superior to IVC combined with focal laser(+5.20 vs+2.71 letters).At month 12,20.83%of the IVC combined with focal laser and 37.04%of IVC combined with focal laser and IVTA arms gained more than 10 BCVA letters.During the period,the mean CRT decreased significantly in the IVC combined with focal laser and IVTA arm(-245.9μm)compared to the IVC combined with focal laser arm(-98.45μm).The average of 6.45 and 1.25 conbercept injections performed in the IVC combined with focal laser and IVC combined with focal laser and IVTA arms,respectively.The mean cost of treatment burden for 12 mo was$6247.44±4069.18 in the IVC combined with focal laser arm and$1679.19±542.73 in the IVC combined with focal laser and IVTA arm,with a statistically significant difference.Apart from occasional minor subconjunctival hemorrhage,no other significant ocular adverse events(AEs)were observed in either group during the 12-month period.CONCLUSION:It is effective and cost-effective to treat DME by utilizing triamcinolone as an adjunct to the combination of anti-VEGF.

Primary conjunctival tuberculosis in two middle-aged women

Dear Editor, We are writing to present two case reports on primary conjunctival tuberculosis(TB)in twomiddle-aged women.TB is an airborne communicable disease and is identified as the second leading cause of death from infectious disease worldwide^([1]). TB primarily affects the lung,butmay also affects extrapulmonary organs, including the eye^([2]).

Effect of palmitoylethanolamide on degeneration of a human-derived retinal pigment epithelial cell induced by all-trans retinal

AIM:To study the effect of palmitoylethanolamide(PEA)on apoptosis of retinal pigment epithelial(RPE)cells induced by all-trans retinal(at RAL)and to explore the possible molecular mechanism.METHODS:Cell Titer 96■Aqueous One Solution Cell Proliferation Assay(MTS)was used to detect the effect of PEA on human-derived retinal epithelial cells(ARPE-19)viability induced by at RAL.A Leica DMi8 inverted microscope was used to observe cell morphology.Reactive oxygen species(ROS)production was evaluated with 2’,7’-dichlorodihydrofluorescein diacetate(H2DCFDA)staining and fluorescence microscopy.Expression of c-Jun N-terminal kinase(JNK),phosphorylated JNK(p-JNK),c-Jun,phosphorylated c-Jun(p-c-Jun),Bak,cleaved caspase-3,C/EBP homologous protein(CHOP),and binding(Bip)protein levels were tested by Western blot.Abca4-/-Rdh8-/-mice,mouse models of at RAL clearance defects which displays some symbolic characteristics of dry age-related macular degeneration(AMD)and Stargardt disease(STGD1).In the animal models,PEA was injected intraperitoneally.The full-field electroretinogram was used to detect visual function under scotopic conditions traced from mice.Optical coherence tomography showed reconstitution or thickening of the retinal pigment epithelium layer.Effect of PEA on fundus injury induced by light in Abca4-/-Rdh8-/-mice was observed by fundus photography.RESULTS:PEA ameliorated ARPE-19 cells apoptosis and inhibited ROS(including mitochondrial ROS)production induced by at RAL.PEA improved the retinal functional,prohibited both RPE and photoreceptor from death,ameliorates light-induced fundus impairment in Abca4-/-Rdh8-/-mice.In vitro and in vivo,PEA inhibited JNK,p-JNK,c-Jun,p-c-Jun,Bak,cleaved caspase-3,CHOP,and Bip protein levels induced by all-trans retinal in ARPE-19 cells.CONCLUSION:PEA has effect on treating RPE cells apoptosis in retinopathy caused by at RAL accumulation.PEA is a potential treatment strategy for dry AMD and STGD1.The molecular mechanism is affecting the ROS-JNKCHOP signaling pathway partly.