Outcomes and risk factors for failure of trabeculectomy in glaucomatous patients in Southwest China:a 325 eyes analysis

AIM:To evaluate the outcomes and elucidate the failure factors for trabeculectomy with mitomycin C(MMC)in Southwest Chinese patients.METHODS:A retrospective correlational study was conducted on the glaucomatous patients who underwent initial trabeculectomy with MMC in Southwest Hospital and had been followed up for 1-3y.A complete success for surgery is defined as a postoperative intraocular pressure(IOP)>5 and≤21 mm Hg and 20%reduction of IOP compared to preoperative,without IOP-lowering medications.A qualified success for surgery is defined as the abovementioned postoperative IOP with or without IOP-lowering medications.The primary outcomes were IOP,the number of IOP-lowering medications,and cumulative success rate.The secondary outcomes included best corrected visual acuity(BCVA),mean deviation(MD)of visual field,major complications,and risk factors for surgical failure.RESULTS:A total of 325 eyes of 261 glaucomatous patients had been included in our study.Both the mean IOP and the number of IOP-lowering medications were significantly decreased from 32.9±12.0 to 16.4±5.7 mm Hg(P<0.0001)and 3.0±0.9 to 0.9±1.0(P<0.0001),respectively,at the last visit.The cumulative complete success rate and qualified success rate were 77.8%and 92.0%at 1-year follow-up,and 47.2%and 77.7%at 3-year follow up.There were no significant differences in surgical outcomes between primary angle-closure glaucoma(PACG)and primary open angle glaucoma(POAG).In PACG patients,the success rates of trabeculectomy were comparable with those of phacotrabeculectomy.Hypertension(HR=1.904,P=0.011),encapsulated bleb(HR=2.756,P<0.001),and more preoperative topical medications(HR=2.475,P=0.008)were risk factors for surgical failure.CONCLUSION:The qualified success rate of trabeculectomy with MMC in glaucomatous patients in the cohort is 92.0%at 1-year,and 77.7%at 3-year follow up.Hypertension,encapsulated bleb,and more preoperative topical medications are associated with surgical failure.

Pediatric ocular trauma with pars plana vitrectomy in Southwest of China:clinical characteristics and outcomes

AIM:To investigate the clinical characteristics and predictive factors of pediatric ocular trauma patients with vitrectomy.METHODS:Pediatric ocular trauma patients(aged 14 y or younger)who received vitrectomy in Southwest Hospital between January 2007 and December 2017 were reviewed retrospectively.Age,gender,mechanism of injury,final visual acuity(VA),and prognostic factors were analyzed.RESULTS:A total of 139 eyes in 139 pediatric patients were included in the study.The mean age was 7.4±3.7 years old and the male-to-female ratio was 5:1.There were 104(74.8%)open globe injuries and 35(25.2%)closed globe injuries.The top one traumatic eye injuries were penetrating injuries occur through sharp metal objects(43.9%).After vitrectomy,116 patients had favorable anatomic outcome at the last follow-up,and 30 eyes(21.6%)achieved VA of 20/200 or better.Following univariate analysis,we found zone III injuries(P=0.021),poor initial VA(P=0.005),endophthalmitis(P=0.024),and recurrent retinal detachment(P<0.001)were poor prognostic factors for pediatric ocular trauma.After Logistic regression analysis,the poor initial VA(odds ratio:8.276,95%CI:1.597-42.897,P=0.012)and recurrent retinal detachment(odds ratio:6.455,95%CI:2.372-17.562,P<0.001)were significantly correlated with unfavorable vision outcome in pediatric ocular trauma.CONCLUSION:The treatment of vitrectomy for severe ocular trauma results in favorable anatomic outcomes,but VA improvement is not as good as anatomic outcomes.Initial VA and recurrent retinal detachment are the independent prognostic indicators for unfavorable visual outcome of severe pediatric ocular trauma.

Human brain organoid:trends,evolution,and remaining challenges

Advanced brain organoids provide promising platforms for deciphering the cellular and molecular processes of human neural development and diseases.Although various studies and reviews have described developments and advancements in brain organoids,few studies have comprehensively summarized and analyzed the global trends in this area of neuroscience.To identify and further facilitate the development of cerebral organoids,we utilized bibliometrics and visualization methods to analyze the global trends and evolution of brain organoids in the last 10 years.First,annual publications,countries/regions,organizations,journals,authors,co-citations,and keywords relating to brain organoids were identified.The hotspots in this field were also systematically identified.Subsequently,current applications for brain organoids in neuroscience,including human neural development,neural disorders,infectious diseases,regenerative medicine,drug discovery,and toxicity assessment studies,are comprehensively discussed.Towards that end,several considerations regarding the current challenges in brain organoid research and future strategies to advance neuroscience will be presented to further promote their application in neurological research.

Development and Validation of an Automatic Ultrawide-Field Fundus Imaging Enhancement System for Facilitating Clinical Diagnosis:A Cross-Sectional Multicenter Study

In ophthalmology,the quality of fundus images is critical for accurate diagnosis,both in clinical practice and in artificial intelligence(AI)-assisted diagnostics.Despite the broad view provided by ultrawide-field(UWF)imaging,pseudocolor images may conceal critical lesions necessary for precise diagnosis.To address this,we introduce UWF-Net,a sophisticated image enhancement algorithm that takes disease characteristics into consideration.Using the Fudan University ultra-wide-field image(FDUWI)dataset,which includes 11294 Optos pseudocolor and 2415 Zeiss true-color UWF images,each of which is rigorously annotated,UWF-Net combines global style modeling with feature-level lesion enhancement.Pathological consistency loss is also applied to maintain fundus feature integrity,significantly improving image quality.Quantitative and qualitative evaluations demonstrated that UWF-Net outperforms existing methods such as contrast limited adaptive histogram equalization(CLAHE)and structure and illumination constrained generative adversarial network(StillGAN),delivering superior retinal image quality,higher quality scores,and preserved feature details after enhancement.In disease classification tasks,images enhanced by UWF-Net showed notable improvements when processed with existing classification systems over those enhanced by StillGAN,demonstrating a 4.62%increase in sensitivity(SEN)and a 3.97%increase in accuracy(ACC).In a multicenter clinical setting,UWF-Net-enhanced images were preferred by ophthalmologic technicians and doctors,and yielded a significant reduction in diagnostic time((13.17±8.40)s for UWF-Net enhanced images vs(19.54±12.40)s for original images)and an increase in diagnostic accuracy(87.71%for UWF-Net enhanced images vs 80.40%for original images).Our research verifies that UWF-Net markedly improves the quality of UWF imaging,facilitating better clinical outcomes and more reliable AI-assisted disease classification.The clinical integration of UWF-Net holds great promise for enhancing diagnostic processes and patient care in ophthalmology.

Proteomic profiling of early degenerative retina of RCS rats

AIM： To identify the underlying cellular and molecular changes in retinitis pigmentosa （RP）. METHODS： Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins （DEPs）. Bioinformatics analyses, including Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. RESULTS： In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student＇s t-test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. CONCLUSION： We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

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.

Biosafety of a 3D-printed intraocular lens made of a poly (acrylamide-co-sodium acrylate) hydrogel in vitro and in vivo

AIM:To assess the biosafety of a poly(acrylamide-cosodium acrylate)hydrogel(PAH)as a 3D-printed intraocular lens(IOL)material.METHODS:The biosafety of PAH was first evaluated in vitro using human lens epithelial cells(LECs)and the ARPE19 cell line,and a cell counting kit-8(CCK-8)assay was performed to investigate alterations in cell proliferation.A thin film of PAH and a conventional IOL were intraocularly implanted into the eyes of New Zealand white rabbits respectively,and a sham surgery served as control group.The anterior segment photographs,intraocular pressure(IOP),blood parameters and electroretinograms(ERG)were recorded.Inflammatory cytokines in the aqueous humor,such as TNFαand IL-8,were examined by ELISA.Cell apoptosis of the retina was investigated by TUNEL assay,and macro PAHge activation was detected by immunostaining.RESULTS:PAH did not slow cell proliferation when cocultured with human LECs or ARPE19 cells.The implantation of a thin film of a 3 D-printed IOL composed of PAH did not affect the IOP,blood parameters,ERG or optical structure in any of the three experimental groups(n=3 for each).Both TNFαand IL-8 in the aqueous humor of PAH group were transiently elevated 1 wk post-operation and recovered to normal levels at 1 and 3 mo post-operation.Iba1+macroPAHges in the anterior chamber angle in PAH group were increased markedly compared to those of the control group;however,there was no significant difference compared to those in the IOL group.CONCLUSION:PAH is a safe material for 3D printing of personal IOLs that hold great potential for future clinical applications.

Fourier-domain optical coherence tomography-guided phototherapeutic keratectomy for the treatment of anterior corneal scarring

AIM:To evaluate the safety,visual and anatomic outcomes of fourier-domain optical coherence tomography(FD-OCT)-guided excimer laser phototherapeutic keratectomy(PTK)combined with photorefractive keratectomy(PRK)surgery in treating anterior corneal scarring.METHODS:Clinical data of 23 eyes of 21 patients with anterior corneal scarring underwent FD-OCT-guided PTK and PRK from Dec.2014 to Jul.2016 were reviewed.Patients were assessed for preoperative and postoperative uncorrected visual acuity(UCVA),best spectacle-corrected visual acuity(BSCVA),contrast sensitivity(CS),FD-OCT,corneal topography and colour figures of anterior segments.RESULTS:The preoperative corneal pathologic conditions included viral keratitis(7 patients,7 eyes),band keratopathy(2 patients,4 eyes),corneal dystrophy(4 patients,4 eyes),traumatic corneal disease(2 patients,2 eyes)and corneal chemical injury(6 patients,6 eyes).Mean follow-up time was 10.65(range,3-19)mo.UCVA(in IogMAR)improved from a mean of 0.79(95%Cl,0.28­1.29)preoperatively to a mean of 0.45(95%Cl,0.29-0.62)postoperatively(P=0.021).BSCVA(in IogMAR)improved from 0.57(95%Cl,0.27-0.88)preoperatively to a mean of 0.28(95%Cl,0.15-0.41)postoperatively(P=0.001).Corneal topographic indices postoperatively showed significant improvement in corneal cylinder(P=0.009),the surface regularity index(P=0.007)and surface asymmetry index(P=0.00).Postoperative spherical equivalent averaged-0.53 diopters(-1.49 to 0.42).No complications were associated with the treatment.CONCLUSION:FD-OCT-guided PTK combined with PRK is safe and effective for the treatment of anterior corneal scarring by eliminating or reducing corneal opacities.

Pupillary capture following sutureless scleral-fixated intraocular lens in children with Marfan syndrome

AIM:To compare the clinical outcomes between two approaches for sutureless scleral-fixated intraocular lens(SFIOL)in children with Marfan syndrome(MFS).METHODS:The study included 15 children(26 eyes)with lens subluxation due to MFS.These children underwent lensectomy,anterior vitrectomy,and sutureless SFIOL.According to the position of placement of intraocular lens(IOL)haptics,two study groups were reviewed for best corrected visual acuity(BCVA)and postoperative complications:group A,14 eyes with haptics fixated at 2.0 mm from the limbus;group B,12 eyes with the haptics fixated at 2.5 mm from the limbus.RESULTS:The mean axial length for all patients was 25.66±2.35 mm.Postoperative BCVA in logMAR were significant improved in both groups(0.77±0.32 to 0.17±0.12 in group A,0.66±0.25 to 0.24±0.12 in group B,both P<0.001)while no significant difference between two groups(P>0.05).Pupillary capture was main postoperative complication,occurring between 3d and 18mo.It occurred in 7 eyes in group A and one eye in group B(P=0.02).CONCLUSION:Sutureless SFIOL is an effective treatment approach for lens subluxation in children with MFS.Pupillary capture is the main postoperative complication.Fixated IOL haptics at 2.5 mm from the limbus can reduce the occurrence of pupillary capture.

Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve

AIM：To explore the effects of αA-crystallin in astrocyte gliosis after optic nerve crush（ONC） and the mechanism of α-crystallin in neuroprotection and axon regeneration.METHODS：ONC was established on the SpragueDawley rat model and αA-crystallin（10 -4 g/L,4 μL） was intravitreously injected into the rat model.Flash-visual evoked potential（F-VEP） was examined 14 d after ONC,and the glial fibrillary acidic protein（GFAP） levels in the retina and crush site were analyzed 1,3,5,7 and 14 d after ONC by immunohistochemistry（IHC） and Western blot respectively.The levels of beta Tubulin（TUJ1）,growth-associated membrane phosphoprotein-43（GAP-43）,chondroitin sulfate proteoglycans（CSPGs） and neurocan were also determined by IHC 14 d after ONC.RESULTS：GFAP level in the retina and the optic nerve significantly increased 1d after ONC,and reached the peak level 7d post-ONC.Injection of αA-crystallin significantly decreased GFAP level in both the retina and the crush site 3d after ONC,and induced astrocytes architecture remodeling at the crush site.Quantification of retinal ganglion cell（RGC） axons indicated αAcrystallin markedly promoted axon regeneration in ONC rats and enhanced the regenerated axons penetrated into the glial scar.CSPGs and neurocan expression also decreased 14 d after αA-crystallin injection.The amplitude（N1-P1） and latency（P1） of F-VEP were also restored.CONCLUSION：Our results suggest α-crystallin promotes the axon regeneration of RGCs and suppresses the activation of astrocytes.

Binocular form deprivation influences the visual cortex

a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are considered to play a crucial role in synaptic plasticity in the developing visual cortex. In this study, we established a rat model of binocular form deprivation by suturing the rat binocular eyelids before eye-opening at postnatal day 14. During development, the decay time of excitatory postsynaptic currents mediated by a-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors of normal rats became longer after eye- opening; however, the decay time did not change significantly in binocular form deprivation rats. The peak value in the normal group became gradually larger with age, but there was no significant change in the binocular form deprivation group. These findings indicate that binocular form deprivation influences the properties of excitatory postsynaptic currents mediated by a-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat visual cortex around the end of the critical period, indicating that form stimulation is associated with the experience-dependent modification of neuronal synapses in the visual cortex.

Changes in N-methyl-D-aspartate receptor 2A subunit expression caused by binocular form deprivation and chondroitin sulfate proteoglycan degradation

Light deprivation is known to induce a significant decrease in the percentage of N-methyi-D- aspartate receptor 2A subunit （NR2A）-expressing neurons during development. The purpose of this study was to investigate the effects of binocular form deprivation （BFD） and chondroitin sulfate proteoglycan （CSPG） degradation on NR2A expression via an immunohistochemical study, around the end of a critical developmental period. The results show that the positive staining of NR2A in the normal rat visual cortex increases gradually from postnatal 3-5 weeks （P 〈 0.05）, but the changes from 5 weeks to 7 weeks were not significant. The positive staining of NR2A following BFD in the rat visual cortex slightly increased from postnatal 3-7 weeks （P 〉 0.05）. The positive staining of NR2A in the CSPG-treated group was insignificant compared with the BFD group at the same time point from 4 weeks to 7 weeks （P 〉 0.05）. Thus, the effect of BFD on NR2A expression in the rat visual cortex was similar to that of CSPG degradation around the end of the critical developmental period.

Organoid-derived human retinal progenitor cells promote early dedifferentiation of Müller glia in Royal College of Surgeons rats

AIM:To explore whether the subretinal transplantation of retinal progenitor cells from human embryonic stem cell-derived retinal organoid(h ERO-RPCs)could promote Müller glia dedifferentiation and transdifferentiation,thus improving visual function and delaying retinal degenerative progression.METHODS:h ERO-RPCs were subretinally transplanted into Royal College of Surgeons(RCS)rats.Electroretinography(ERG)recording was performed at 4 and 8wk postoperation to assess retinal function.Using immunofluorescence,the changes in outer nuclear layer(ONL)thickness and retinal Müller glia were explored at 2,4,and 8wk postoperation.To verify the effect of h ERO-RPCs on Müller glia in vitro,we cocultured h ERO-RPCs with Müller glia with a Transwell system.After coculture,Ki67 staining and quantitative polymerase chain reaction(q PCR)were performed to measure the proliferation and m RNA levels of Müller glia respectively.Cell migration experiment was used to detect the effect of h ERO-RPCs on Müller glial migration.Comparisons between two groups were performed by the unpaired Student’s t-test,and comparisons among multiple groups were made with one-way ANOVA followed by Tukey’s multiple comparison test.RESULTS:The visual function and ONL thickness of RCS rats were significantly improved by transplantation of h ERO-RPCs at 4 and 8wk postoperation.In addition to inhibiting gliosis at 4 and 8wk postoperation,h ERO-RPCs significantly increased the expression of dedifferentiation-associated transcriptional factor in Müller glia and promoted the migration at 2,4 and 8wk postoperation,but not the transdifferentiation of these cells in RCS rats.In vitro,using the Transwell system,we found that h ERO-RPCs promoted the proliferation and migration of primary rat Müller glia and induced their dedifferentiation at the m RNA level.CONCLUSION:These results show that h ERO-RPCs might promote early dedifferentiation of Müller glia,which may provide novel insights into the mechanisms of stem cell therapy and Müller glial reprogramming,contributing to the development of novel therapies for retinal degeneration disorders.

Changes in intrinsic excitability of ganglion cells in degenerated retinas of RCS rats

AIM：To evaluate the intrinsic excitability of retinal ganglion cells（RGCs） in degenerated retinas.METHODS：The intrinsic excitability of various morphologically defined RGC types using a combination of patch-clamp recording and the Lucifer yellow tracer in retinal wholemount preparations harvested from Royal College of Surgeons（RCS） rats,a common retinitis pigmentosa（RP） model,in a relatively late stage of retinal degeneration（P90） were investigated.Several parameters of RGC morphologies and action potentials（APs） were measured and compared to those of non-dystrophic control rats,including dendritic stratification,dendritic field diameter,peak amplitude,half width,resting membrane potential,AP threshold,depolarization to threshold,and firing rates.RESULTS：Compared with non-dystrophic control RGCs,more depolarizations were required to reach the AP threshold in RCS RGCs with low spontaneous spike rates and in RCS OFF cells（especially A2o cells）,and RCS RGCs maintained their dendritic morphologies,resting membrane potentials and capabilities to generate APs.CONCLUSION：RGCs are relatively well preserved morphologically and functionally,and some cells are more susceptible to decreased excitability during retinal degeneration.These findings provide valuable considerations for optimizing RP therapeutic strategies.

Development-related mitochondrial properties of retinal pigment epithelium cells derived from hEROs

AIM:To explore the temporal mitochondrial characteristics of retinal pigment epithelium(RPE)cells obtained from human embryonic stem cells(hESC)-derived retinal organoids(hEROs-RPE),to verify the optimal period for using hEROs-RPE as donor cells from the aspect of mitochondria and to optimize RPE cell-based therapeutic strategies for age-related macular degeneration(AMD).METHODS:RPE cells were obtained from hEROs and from spontaneous differentiation(SD-RPE).The mitochondrial characteristics were analyzed every 20 d from day 60 to 160.Mitochondrial quantity was measured by MitoTracker Green staining.Transmission electron microscopy(TEM)was adopted to assess the morphological features of the mitochondria,including their distribution,length,and cristae.Mitochondrial membrane potentials(MMPs)were determined by JC-1 staining and evaluated by flow cytometry,reactive oxygen species(ROS)levels were evaluated by flow cytometry,and adenosine triphosphate(ATP)levels were measured by a luminometer.Differences between two groups were analyzed by the independentsamples t-test,and comparisons among multiple groups were made using one-way ANOVA or Kruskal-Wallis H test when equal variance was not assumed.RESULTS:hEROs-RPE and SD-RPE cells from day 60 to 160 were successfully differentiated from hESCs and expressed RPE markers(Pax6,MITF,Bestrophin-1,RPE65,Cralbp).RPE features,including a cobblestonelike morphology with tight junctions(ZO-1),pigments and microvilli,were also observed in both hEROs-RPE and SDRPE cells.The mitochondrial quantities of hEROs-RPE and SD-RPE cells both peaked at day 80.However,the cristae of hEROs-RPE mitochondria were less mature and abundant than those of SD-RPE mitochondria at day 80,with hEROsRPE mitochondria becoming mature at day 100.Both hEROs-RPE and SD-RPE cells showed low ROS levels from day 100 to 140 and maintained a normal MMP during this period.However,hEROs-RPE mitochondria maintained a longer time to produce high levels of ATP(from day 120 to 140)than SD-RPE cells(only day 120).CONCLUSION:hEROs-RPE mitochondria develop more slowly and maintain a longer time to supply high-level energy than SD-RPE mitochondria.From the mitochondrial perspective,hEROs-RPE cells from day 100 to 140 are an optimal cell source for treating AMD.

The effect of clinical-grade retinal pigment epithelium derived from human embryonic stem cells using different transplantation strategies

Dear Editor, Many forms of sight-threatening diseases, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD), are caused by the dysfunction, degeneration and loss of the retinal pigment epithelium (RPE)(Strauss, 2005). RPE cell transplantation may potentially recover or halt disease progression, in which human embryonic stem cells (hESCs) could serve as an unlimited donor source for RPE differentiation, and a few clinical trials have shown the safety and effective of transplantation of hESCs-derived RPE (hESC-RPE) for AMD patients (Schwartz et al., 2012;Schwartz etal., 2015;Song etal., 2015;da Cruz et al., 2018;Kashani et al., 2018;Liu et al., 2018).

Toxicity of silicon dioxide nanoparticles with varying sizes on the cornea and protein corona as a strategy for therapy

The human cornea is exposed directly to particulate matter （PM） in polluted air. This exposure can cause eye discomfort and corneal injury. Ultrafine PM （diameter ~100 nm） is thought to be particularly harmful to health, but there is limited research investigating its toxicity to the eye. In this study, we evaluated toxiciW differences among 30-, 40-, 100- and 150-nm silicon dioxide nanoparticles （Si02 NPs） on the cornea. A 24-hour in vitro exposure of primary human corneal epithelial cells （hCECs） to ultrafine （30 and 40 nm） SiO2 NPs produced toxicity, as evidenced by cell membrane damage, reduced cell viability, increased cell death and mitochondrial dysfunction. In vivo exposure to the same nanoparticles produced observable corneal injury. These effects were more severe with ultrafine than with fine （100 and 150 nm） Si02 NPs. Common antioxidant compounds, e.g., glutathione, did not protect the cornea from SiO2 NP-induced damage. However, foetal bovine serum （FBS） did significantly reduce toxicity, likely by forming a protective protein corona around the nanoparticles. This finding suggests that FBS （or its derivatives） may be a useful clinical therapy for corneal toxicity caused by ultrafine particulates.