Anterior and posterior segment structural features of acute primary angle-closure eyes:date based on AS-OCT and SS-OCT

Background:To measure the anterior and posterior segment structural features of acute primary angle-closure(APAC)eyes.Methods:A total of 36 subjects with unilateral APAC were recruited in this study.The ocular biometric characteristics were measured by anterior segment optical coherence tomography(AS-OCT)and swept source optical coherence tomography(SS-OCT),respectively at baseline,2 weeks,and 1 month after surgical intervention.Results:At baseline,when compared with the fellow eyes,APAC-affected eyes showed significantly greater corneal thickness(P=0.004),shallower anterior chamber depth(ACD)(P<0.001),smaller anterior chamber area(ACA)(P=0.013),angle opening distance at 750μm from the scleral spur(AOD750)(P=0.002),trabecular-iris space area at 750μm from the scleral spur(TISA750)(P=0.033),angle recess area(ARA)(P=0.014),and iris area(IARE)(P=0.003),less iris curvature(ICURVE)(P=0.003),and larger lens vault(LV)(P=0.030).After intervention,the corneal thickness was significantly decreased at 1 month(P<0.001),while ACD,ACA,and AOD750 were significantly increased at 2 weeks and 1 month(all P<0.017).Changes in ACD were correlated with decreasing LV(P<0.05).The posterior segment parameters did not change over the 4-week period.Conclusions:When compared with the fellow eyes,APAC-affected eyes had greater corneal thickness,shallower anterior chamber,narrower angle,less ICURVE,and larger LV.After intervention,the corneal thickness was decreased,while the shallower anterior chamber was relieved to some extent.

Treatment of superficial corneal opacities with corneal stromal lenticule obtained through SMILE surgery

AIM:To evaluate the clinical efficacy and feasibility of superficial corneal opacities treated by excimer laser phototherapeutic keratectomy(PTK)combined with small incision lenticule extraction(SMILE)-derived corneal stromal lenticule transplantation.METHODS:A retrospective interventional case series of nine patients aged 12-59y with superficial corneal opacity caused by different pathologies who underwent standardized PTK combined with SMILE-derived corneal stromal lenticule transplantation was examined.Lenticule patches were fixed with fibrin glue.All patients underwent pre-and post-operative clinical assessments at different times for up to 12mo.Slit lamp microscopy,corneal density,uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA),and anterior segment optical coherence tomography(AS-OCT)were examined.RESULTS:The patients’mean age was 36.00±5.80(12-59)y.Seven eyes(77.8%)gained UDVA and CDVA at the last measurement compared to their preoperative levels.The densities of the total cornea,the total anterior corneal layer,and the anterior corneal layers of 0-2 and 2-6 mm decreased significantly by 12.4%,27.5%,46.7%,and 32.8%,respectively.After human allogeneic transplantation,the implanted lenticules of all eyes were clearly visible by AS-OCT and remained transparent without displacement or graft rejection.The thickness of the central cornea and corneal lenticule transplants were stable throughout the entire postoperative period.One case experienced the postoperative complication of delayed corneal epithelial healing.CONCLUSION:PTK combined with SMILE-derived corneal lenticule transplantation improves long-term visual acuity.Therefore,it is a new,safe,and effective method for treating superficial corneal opacity.

Application of Preoperative Visits during the Perioperative Period of Ophthalmic Surgery

Purpose:.To evaluate the effect of preoperative visits on patients′ psychology, physiology, and behavior during the perioperative period of eye surgery under local anesthesia, with the aim of enhancing patients′ cooperation with the surgery and improving their degree of satisfaction.Methods:.A total of 240 patients scheduled to undergo eye surgery between August and October 2013 were randomly divided into an observation(n = 120) and a control(n = 120)group..Patients in the observation group attended preoperative visits with nurses and received conventional nursing care. The control group received only conventional nursing.Results:.The Zung self-rating anxiety scale(SAS) scores were significantly lower in patients from the observation group than in the control group(P<0.05). Surgeons operating on the observation group were more satisfied with their patients′ cooperation with the surgery than were surgeons operating on the controls(P<0.01). Patients in the observation group had a significantly higher degree of satisfaction in terms of work efficiency in the operating room(P<0.01).Conclusion:.Preoperative visits by patients scheduled to undergo eye surgery can effectively mitigate preoperative anxiety in those patients,.build up a positive attitude toward the upcoming surgery,.instruct the patients to coordinate with the surgery,.enhance surgical safety,.and improve the patients′degree of satisfaction regarding the nursing care in the operating room.

Comparison of corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus

AIM:To evaluate the differences in corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus.METHODS:In our prospective clinical trial,40 patients(60 eyes)with progressive keratoconus were randomized to undergo corneal cross-linking with transepithelial(TE group,n=30)or epithelium-off(EO group,n=30)keratoconus.Examinations comprised topography,corneal biomechanical analysis and specular microscopy at 6 mo postoperatively.RESULTS:The keratometer values were not significantly different between the TE and EO corneal cross-linked groups in different periods(each P>0.05).The corneal thickness of the EO group was greater than that of the TE group at 1 wk after the operation(each P<0.05).Regarding corneal biomechanical responses,the EO group showed a longer second applanation length than TE group(P=0.003).Regarding the corneal endothelial function,standard deviation of the endothelial cell size,and coefficient of variation in the cell area,the values of EO group were larger than those of TE group at 1 wk(P=0.011,0.026),and the percentage of hexagonal cells in EO group was lower than that in TE group at 1 and 6 mo(P=0.018,0.019).CONCLUSION:Epithelium-off corneal cross-linking may strengthen corneal biomechanics better than TE procedure can.However,the TE procedure with a lower ultraviolet-A irradiation intensity would be safer for corneal endothelial function.

Comparison of early changes in ocular surface markers and tear inflammatory mediators after femtosecond lenticule extraction and FS-LASIK

AIM:To compare the short-term impacts of femtosecond lenticule extraction(FLEx)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)on ocular surface measures and tear inflammatory mediators.METHODS:This prospective comparative nonrandomized clinical study comprised 75 eyes(75 patients).Totally 20 male and 15 female patients(age 21.62±3.25 y)with 35 eyes underwent FLEx,and 26 male and 14 female patients(age 20.18±3.59 y)with 40 eyes underwent FS-LASIK.Central corneal sensitivity,noninvasive tear breakup time,corneal fluorescein staining,Schirmer I test,tear meniscus height,and ocular surface disease index were evaluated in all patients.Tear concentrations of nerve growth factor(NGF),interleukin-1α(IL-1α),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and matrix metalloproteinase-9(MMP-9)were assessed by multiplex antibody microarray.All measurements were performed preoperatively,and 1 d,1 wk,and 1 mo postoperatively.RESULTS:Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1 wk after the procedure(P<0.01).NGF was significantly higher 1 d and 1 wk after surgery in the FS-LASIK group than in the FLEx group(P<0.01).By contrast,compared to those in the FLEx group,higher postoperative values and slower recovery of tear TGF-β1,IL-1α,and TNF-αconcentrations were observed in the FS-LASIK group(P<0.01).Tear concentrations of NGF,TGF-β1,TNF-α,and IL-1αwere correlated with ocular surface changes after FLEx or FS-LASIK surgery.CONCLUSION:There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK.NGF,TGF-β1,TNF-α,and IL-1αmay contribute to the process of ocular surface recovery.

Effects of curcumin nanoparticles on proliferation and VEGF expression of human retinal pigment epithelial cells

AIM:To investigate the effects of curcumin(Cur)nanoparticles loaded with chitosan derivatives grafted by deoxycholic acid(Chit-DC)on human retinal pigment epithelial(h RPE)cell proliferation and vascular endothelial growth factor(VEGF)m RNA expression.METHODS:Cur nanoparticles were synthesized with Chit-DC as the carrier and Cur as the supported drug.Cell counting kit-8(CCK-8)method was used to detect the effects of different concentrations of Cur/Chit-DC,Chit-DC,and Cur on the proliferation of h RPE cells for different times.The changes of Cur/Chit-DC and Cur on h RPE cell cycle were determined by flow cytometry.Semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the m RNA expression levels of VEGF in h RPE cells treated with Cur,Chit-DC and Cur/Chit-DC at 10μg/m L for 24 h.RESULTS:Different concentrations of Chit-DC nanoparticle treated h RPE cells had no significant difference in terms of optical density(OD)values compared with the control group at 24 h and 48 h.Moreover,there was no change in the cell morphology under a light microscope.After 24 h treatment with Cur/Chit-DC and Cur,the percentage of G0-G1 phase cells increased and the percentage of S phase cells decreased in all concentration groups.Cur/Chit-DC and Cur in all concentration groups inhibited the proliferation of h RPE cells in a time and dose dependent manner,and reduced the expression level of VEGF m RNA.CONCLUSION:The Cur/Chit-DC nanoparticles can release Cur continuously and have sustained release function.Both Cur/Chit-DC nanoparticles and Cur could inhibit h RPE cells cultured in vitro,and could reduce the expression level of VEGF m RNA in h RPE cells.

Overhanging glaucoma filtration bleb related to cataract surgery

A 74-year-old man presented with a three-year history of foreign body sensation in the right eye after cataract surgery.He underwent uneventful trabeculectomy with mitomycin C(MMC) in the right eye seven years ago.Slit-lamp examination revealed a large avascular filtration bleb overhanging on the cornea with a thin base connected to the conjunctiva.Preoperative ultrasound biomicroscopy(UBM) impressions were confirmed by leakage of aqueous from the incision intraoperatively.Surgical dissection and revision of the bleb was performed with satisfactory outcome.Histopathologic evaluation showed proliferation of fibrous tissue under the conjunctival epithelia with irregular cystoids change.The current case may be the first report of a post-trabeculectomy overhanging filtration bleb related to cataract surgery.The possible mechanism may be related to microleakage of the surgical wound after phacoemulsification which initiated the healing and scarring process.

Short term effects of small incision lenticule extraction surgery on corneal endothelium

AIM： To assess the effects of small incision lenticule extraction（SMILE） surgery on the corneal endothelium at1 d to 1mo postoperatively.·METHODS： A retrospective, observational study was conducted on 47 patients（47 eyes） who received SMILE surgery. Patients were grouped according to contact lens wear condition. The corneal endothelium was examined preoperatively and at 1d, 1wk and 1mo postoperatively.The corneal endothelium was analyzed for endothelial cell density（ECD）, percentage of hexagonal cells, and coefficient of variation（CV） of cell size.·RESULTS： There were no significant decrease in the ECD, percentage of hexagonal cells or increase in CV at1 d, 1wk and 1mo postoperatively（P 〉0.05）. However,there was a small increase of ECD by 2.88% in contact lens wearers（78.26±113.62 cell/mm2, P 〈0.05）.· CONCLUSION： SMILE has no significant adverse effects on the corneal ECD and morphology during 1mo follow-up time.

Association of sensorineural hearing loss and pseudoexfoliation syndrome:a meta-analysis

Background:Previous studies that assessed the association of sensorineural hearing loss(SNHL)and pseudoexfoliation syndrome(PEX)produced contradictory results.We conducted a meta-analysis to further evaluate this relationship.Methods:Eligible studies that evaluated the association between SNHL and PEX were identified.Summary odds ratios(ORs)and 95%confidence intervals(CIs)were calculated employing random-effects models.Subgroup analysis and meta-regression were performed to assess heterogeneity by several covariates.Publication bias was tested by Begg’s funnel plot and Egger’s regression test.Results:A total of 14 eligible studies,involving 1,142 PEX patients and 9,914 controls,were included in this meta-analysis.Overall analysis showed that patients with PEX,when compared with the control group,experienced a significantly increased risk for hearing loss[OR:3.74(95%CI:2.56 to 5.47);P<0.001].Substantial heterogeneity was observed.Subgroup analysis revealed a decrease in this heterogeneity in ageand sex-matched studies and in studies that used the same definition of hearing loss.Meta-regression analysis showed that definition of hearing loss contributed to substantial heterogeneity(P=0.044).No evidence of publication bias was observed.Discussion:We found that PEX is associated with an increased risk of SNHL.The effect of PEX on the prevalence of hearing loss indicates that PEX is clearly a systemic disease with potential otological complications.

Large-Scale Proteome-Wide Mendelian Randomization Identifies Novel Proteins for Glaucoma and Related Traits

Purpose:To identify plasma proteins that are causally related to primary open-angle glaucoma(POAG)for potential therapeutic targeting.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were derived from two extensive genome-wide analysis study(GWAS)datasets and one systematic review,with over 100 thousand participants covering thousands of plasma proteins.POAG data were sourced from the largest FinnGen study,comprising 8,530 DR cases and 391,275 European controls.A two-sample MR analysis,supplemented by bidirectional MR,Bayesian co-localization analysis,and phenotype scanning,was conducted to examine the causal relationships between plasma proteins and POAG.The analysis was validated by identifying associations between plasma proteins and POAG-related traits,including intraocular pressure(IOP),retinal nerve fibre layer(RNFL),and ganglion cell and inner plexiform layer(GCIPL).By searching druggable gene lists,the ChEMBL database,and the ClinicalTrials.gov database,the druggability and clinical development activity of the identified proteins were systematically evaluated.Results:Eighteen proteins were identified with significant associations with POAG risk after multiple comparison adjustments.The ORs per standard deviation increase in protein levels ranged from 0.39(95%CI:0.24–0.62;P=7.70×10^(-5))for phospholipase C gamma 1(PLCG1)to 1.29(95%CI:1.16–1.44;P=6.72×10^(-6))for nidogen-1(NID1).Bidirectional MR indicated that reverse causality did not interfere with the results of the main MR analyses.Five proteins exhibited strong co-localization evidence(PH4≥0.8):protein sel-1 homolog 1(SEL1L),tyrosine-protein kinase receptor UFO(AXL),nidogen-1(NID1)and FAD-linked sulfhydryl oxidase ALR(GFER)were negatively associated with POAG risk,while roundabout homolog 1(ROBO1)showed a positive association.The phenotype scanning did not reveal any confounding factors between pQTLs and POAG.Further,validation analyses identified nine proteins causally related to POAG traits,with five proteins including interleukin-18 receptor 1(IL18R1),interleukin-1 receptor type 1(IL1R1),phospholipase C gamma 1(PLCG1),ribonuclease pancreatic(RNASE1),serine protease inhibitor Kazal-type 6(SPINK6)revealing consistent directional associations.In addition,18 causal proteins were highlighted for their druggability,of which 5 proteins are either already approved drugs or in clinical trials and 13 proteins are novel drug targets.Conclusions:This study identifies 18 plasma proteins as potential therapeutic targets for POAG,particularly emphasizing the role of genomic and proteomic integration in drug discovery.Future experimental and clinical studies should be conducted to validate the efficacy of these proteins and to conduct more comprehensive proteomic explorations,thus taking a significant leap toward innovative POAG treatments.

Machine learning methods for biological age estimation

Age stands as a primary risk factor for diseases and disabilities among the elderly.To effectively assess the underlying aging processes,accurate measures of biological age and rates of aging across multiple levels of aging features are essential.Biological age derives from physiological assessments of systems and organs.It has emerged as a superior predictor of age-related diseases and mortality compared to chronological age.Recent advancements in machine learning have catalyzed the development of sophisticated models capable of quantitatively characterizing biological aging with different types of data.This review explores the machine learning models in advancing our understanding of biological aging,highlighting the potential of these innovative approaches to facilitate aging research and personalized healthcare strategies.

Identification of novel drug targets for diabetic retinopathy:proteome-wide mendelian randomization and colocalization analyses

Background:Diabetic retinopathy(DR)urgently needs novel and effective therapeutic targets.Integrated analyses of plasma proteomic and genetic markers can clarify the causal relevance of proteins and discover novel targets for diseases,but no systematic screening for DR has been performed.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were derived from two extensive genome-wide analysis study(GWAS)datasets and one systematic review,with over 100 thousand participants covering thousands of plasma proteins.DR data were sourced from the largest FinnGen study,comprising 10,413 DR cases and 308,633 European controls.Genetic instrumental variables were identified using multiple filters.In the two-sample MR analysis,Wald ratio and inverse variance-weighted(IVW)MR were utilized to investigate the causality of plasma proteins with DR.Bidirectional MR,Bayesian Co-localization,and phenotype scanning were employed to test for potential reverse causality and confounding factors in the main MR analyses.By systemically searching druggable gene lists,the ChEMBL database,DrugBank,and Gene Ontology database,the druggability and relevant functional pathways of the identified proteins were systematically evaluated.Results:Genetically predicted levels of 24 proteins were significantly associated with DR risk at a false discovery rate<0.05 including 11 with positive associations and 13 with negative associations.For each standard deviation increase in plasm protein levels,the odds ratios(ORs)for DR varied from 0.51(95%CI:0.36-0.73;P=2.22×10-5)for tubulin polymerization-promoting protein family member 3(TPPP3)to 2.02(95%CI:1.44-2.83;P=5.01×10-5)for olfactomedin like 3(OLFML3).Bidirectional MR indicated there was no reverse causality that interfered with the results of the main MR analyses.Four proteins exhibited strong co-localization evidence(PH4≥0.8):cytoplasmic tRNA synthetase(WARS),acrosin binding protein(ACRBP),and intercellular adhesion molecule 1(ICAM1)were negatively associated with DR risk,while neurogenic locus notch homolog protein 2(NOTCH2)showed a positive association.No confounding factors were detected between pQTLs and DR according to the phenotypic scan.Drugability assessments highlighted 6 proteins already in drug development endeavor and 18 novel drug targets,with metalloproteinase inhibitor 3(TIMP)currently in phase I clinical trials for DR.GO analysis identified 18 of 24 plasma proteins enriching 22 pathways related to cell differentiation and proliferation regulation.Conclusions:Twenty-four promising drug targets for DR were identified,including four plasma proteins with particular co-localization evidence.These findings offer new insights into DR's etiology and therapeutic targeting,exemplifying the value of genomic and proteomic data in drug target discovery.

Harnessing AI-human synergy for deep learning research analysis in ophthalmology with large language models assisting humans

Background:Research innovations inocular disease screening,diagnosis,and management have been boosted by deep learning(DL)in the last decade.To assess historical research trends and current advances,we conducted an artificial intelligence(AI)-human hybrid analysis of publications on DL in ophthalmology.Methods:All DL-related articles in ophthalmology,which were published between 2012 and 2022 from Web of Science,were included.500 high-impact articles annotated with key research information were used to fine-tune a large language models(LLM)for reviewing medical literature and extracting information.After verifying the LLM's accuracy in extracting diseases and imaging modalities,we analyzed trend of DL in ophthalmology with 2535 articles.Results:Researchers using LLM for literature analysis were 70%(P=0.0001)faster than those who did not,while achieving comparable accuracy(97%versus 98%,P=0.7681).The field of DL in ophthalmology has grown 116%annually,paralleling trends of the broader DL domain.The publications focused mainly on diabetic retinopathy(P=0.0003),glaucoma(P=0.0011),and age-related macular diseases(P=0.0001)using retinal fundus photographs(FP,P=0.0015)and optical coherence tomography(OCT,P=0.0001).DL studies utilizing multimodal images have been growing,with FP and OCT combined being the most frequent.Among the 500 high-impact articles,laboratory studies constituted the majority at 65.3%.Notably,a discernible decline in model accuracy was observed when categorizing by study design,notwithstanding its statistical insignificance.Furthermore,43 publicly available ocular image datasets were summarized.Conclusion:This study has characterized the landscape of publications on DL in ophthalmology,by identifying the trends and breakthroughs among research topics and the fast-growing areas.This study provides an efficient framework for combined AI-human analysis to comprehensively assess the current status and future trends in the field.

From barn lanterns to the 5G Intelligent Ophthalmic Cruiser:The perspective of artificial intelligence and digital technologies on the modality and efficiency of blindness prevention in China

Blindness prevention has been an important national policy in China.Previous strategies,such as deploying experienced cataract surgeons to rural areas and assisting in building local ophthalmology centers,had successfully decreased the prevalence of visual impairment and blindness.However,new challenges arise with the aging population and the shift of the disease spectrum towards age-related eye diseases and myopia.With the constant technological boom,digital healthcare innovations in ophthalmology could immensely enhance screening and diagnosing capabilities.Artificial intelligence(AI)and telemedicine have been proven valuable in clinical ophthalmology settings.Moreover,the integration of cutting-edge communication technology and AI in mobile clinics and remote surgeries is on the horizon,potentially revolutionizing blindness prevention and ophthalmic healthcare.The future of blindness prevention in China is poised to undergo significant transformation,driven by emerging challenges and new opportunities.

Retinal neurovascular characteristics for the diagnosis and staging of nondiabetic chronic kidney disease:a diagnostic study

Aims:To identify the characteristic retinal neurovascular changes in patients in different stages of nondiabetic chronic kidney disease(CKD)and to develop a model for the accurate diagnosis of nondiabetic CKD.Methods:Peripapillary retinal nerve fiber layer(pRNFL)thickness and average macular ganglion cell-inner plexiform layer(GC-IPL)thickness of nondiabetic CKD patients and healthy controls(HC)were evaluated by spectral-domain optical coherence tomography(OCT).The vessel density(VD)and perfusion density(PD)of the macula were obtained from optical coherence tomography angiography(OCTA).The estimated glomerular filtration rate(eGFR)was obtained to access the kidney function of CKD patients.Multiple linear regression models were used to adjust for confounding factors in statistical analyzes.The diagnostic capabilities of the parameters were evaluated by logistic regression models.Results:131 nondiabetic CKD patients and 62 HC entered the study.eGFR was found significantly associated with parafoveal VD and PD(average PD:β=0.0004,P_(adjusted)<0.001)in various sectors.Thinning of pRNFL(β=−6.725,P_(adjusted)<0.001)and GC-IPL(β=−4.542,P_(adjusted)<0.001),as well as decreased VD(β=−2.107,P_(adjusted)<0.001)and PD(β=−0.057,P_(adjusted)=0.0328)were found in CKD patients.Thinning of pRNFL and deteriorated perifoveal vasculature were found in early CKD,and the parafoveal and foveal VD significantly declined in advanced CKD.Logistic regression models were employed,and selected neurovascular parameters showed an AUC of 0.853(95%CI:0.795 to 0.910)in distinguishing CKD patients from HC.Conclusions:Distinctive retinal neurovascular characteristics could be observed in nondiabetic CKD patients of different severities.Our results suggest that retinal manifestations could be valuable in the screening,diagnosis,and follow-up evaluation of patients with CKD.

Intravitreal brimonidine inhibits formdeprivation myopia in guinea pigs

Background:The use of ocular hypotensive drugs has been reported to attenuate myopia progression.This study explores whether brimonidine can slow myopia progression in the guinea pig form-deprivation(FD)model.Methods:Three-week-old pigmented male guinea pigs(Cavia porcellus)underwent monocular FD and were treated with 3 different methods of brimonidine administration(eye drops,subconjunctival or intravitreal injections).Four different concentrations of brimonidine were tested for intravitreal injection(2μg/μL,4μg/μL,20μg/μL,40μg/μL).All treatments continued for a period of 21 days.Tonometry,retinoscopy,and A-scan ultrasonography were used to monitor intraocular pressure(IOP),refractive error and axial length(AL),respectively.On day 21,guinea pigs were sacrificed for RNA sequencing(RNA-seq)to screen for associated transcriptomic changes.Results:The myopia model was successfully established in FD animals(control eye vs.FD eye,respectively:refraction at day 20,0.97±0.18 D vs.−0.13±0.38 D,F=6.921,P=0.02;AL difference between day 0 and day 21,0.29±0.04mm vs.0.45±0.03 mm,F=11.655,P=0.004).Among the 3 different brimonidine administration methods,intravitreal injection was the most effective in slowing myopia progression,and 4μg/μL was the most effective among the four different concentrations of brimonidine intravitreal injection tested.The AL and the refraction of the brimonidine intravitreal injection group was significantly shorter or more hyperopic than those of other 2 groups.Fourμg/μL produced the smallest difference in AL and spherical equivalent difference values.FD treatment significantly increased the IOP.IOP was significantly lower at 1 day after intravitreal injections which was the lowest in FD eye of intravitreal injection of brimonidine.At day 21,gene expression analyses using RNA-seq showed upregulation of Col1a1 and Mmp2 expression levels by intravitreal brimonidine.Conclusions:Among the 3 different administration methods,intravitreal injection of brimonidine was the most effective in slowing myopia progression in the FD guinea pig model.Intravitreal brimonidine at 4μg/μL significantly reduced the development of FD myopia in guinea pigs.Expression levels of the Col1a1 and Mmp2 genes were significantly increased in the retinal tissues of the FD-Inj-Br group.

ATF4/TXNIP/REDD1/mTOR signaling mediates the antitumor activities of liver X receptor in pancreatic cancers

Background:Limited by difficulties in early detection and availabilities of effective treatments,pancreatic cancer is a highly malignant disease with poor prognosis.Nuclear receptors are a family of ligand‐dependent transcription factors that are highly druggable therapeutic targets playing critical roles in human physiological and pathological development,including cancer.In this study,we explored the therapeutic potential as well as the molecular mechanisms of liver X receptor(LXR)agonist GW3965 in pancreatic cancer.Methods:Soft‐agar colony formation assay,xenograft tumors,Oligonucleotide microarray,Reverse transcription real‐time polymerase chain reaction,Western immunoblotting and Immunohistochemistry were used in this study.Results:We demonstrated pleotropic in vitro activities of GW3965 in pancreatic cell lines MIA PaCa‐2 and BXPC3 including reduction of cell viability,inhibition of cell proliferation,stimulation of cell death,and suppression of colony formation,which translated to significant inhibition of xenograft tumor growth in vitro.By mapping the gene expression profiles,we identified the up‐regulations of 188 and the down‐regulations of 92 genes common to both cell lines following GW3965 treatment.Genes responsive to GW3965 represent a variety of biological pathways vital for multiple cellular functions.Specifically,we identified that the activating transcription factor 4/thioredoxin‐interacting protein/regulated in development and DNA damage responses 1/mechanistic target of rapamycin(ATF4/TXNIP/REDD1/mTOR)signaling critically controls GW3965‐mediated regulation of cell proliferation/death.The significance of the ATF4/TXNIP/REDD1/mTOR pathway was further supported by associated expressions in xenograft tumors as well as human pancreatic cancer samples.Conclusions:This study provides the pre‐clinical evidence that LXR agonist is a promising therapy for pancreatic cancer.

Intravitreal brimonidine inhibits formdeprivation myopia in guinea pigs

Background:The use of ocular hypotensive drugs has been reported to attenuate myopia progression.This study explores whether brimonidine can slow myopia progression in the guinea pig form-deprivation(FD)model.Methods:Three-week-old pigmented male guinea pigs(Cavia porcellus)underwent monocular FD and were treated with 3 different methods of brimonidine administration(eye drops,subconjunctival or intravitreal injections).Four different concentrations of brimonidine were tested for intravitreal injection(2μg/μL,4μg/μL,20μg/μL,40μg/μL).All treatments continued for a period of 21 days.Tonometry,retinoscopy,and A-scan ultrasonography were used to monitor intraocular pressure(IOP),refractive error and axial length(AL),respectively.On day 21,guinea pigs were sacrificed for RNA sequencing(RNA-seq)to screen for associated transcriptomic changes.Results:The myopia model was successfully established in FD animals(control eye vs.FD eye,respectively:refraction at day 20,0.97±0.18 D vs.−0.13±0.38 D,F=6.921,P=0.02;AL difference between day 0 and day 21,0.29±0.04mm vs.0.45±0.03 mm,F=11.655,P=0.004).Among the 3 different brimonidine administration methods,intravitreal injection was the most effective in slowing myopia progression,and 4μg/μL was the most effective among the four different concentrations of brimonidine intravitreal injection tested.The AL and the refraction of the brimonidine intravitreal injection group was significantly shorter or more hyperopic than those of other 2 groups.Fourμg/μL produced the smallest difference in AL and spherical equivalent difference values.FD treatment significantly increased the IOP.IOP was significantly lower at 1 day after intravitreal injections which was the lowest in FD eye of intravitreal injection of brimonidine.At day 21,gene expression analyses using RNA-seq showed upregulation of Col1a1 and Mmp2 expression levels by intravitreal brimonidine.Conclusions:Among the 3 different administration methods,intravitreal injection of brimonidine was the most effective in slowing myopia progression in the FD guinea pig model.Intravitreal brimonidine at 4μg/μL significantly reduced the development of FD myopia in guinea pigs.Expression levels of the Col1a1 and Mmp2 genes were significantly increased in the retinal tissues of the FD-Inj-Br group.