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.

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.

人工智能在眼前节疾病诊断中的应用指南(2023)

本文旨在深入探讨人工智能(artificial intelligence,AI)在眼科眼前节疾病诊断中的应用指南。由于眼前节疾病研究所涉及的图像较为复杂多变,AI既往在眼科主要应用于眼后段疾病,但随着AI技术的提升,尤其是机器学习和深度学习的发展,再加上眼前节电子影像数据的指数级增长,AI在角膜、结膜、晶状体和眼睑疾病领域的应用成为现实。中国医药教育协会眼科影像与智能医疗分会和国际转化医学会眼科专业委员会组织专家们结合近年来国内外AI在眼前节疾病诊断中的最新进展,包括在角膜、结膜、晶状体和眼睑疾病的应用,并分析当前面临的挑战和未来的发展方向,经过多轮讨论和修改,形成了该指南,旨在辅助眼科临床医生更好地应用AI进行眼前节疾病的诊断决策及临床研究。

Netrin-1 promotes epithelium repair in corneal injury

●AIM:To explore netrin-1 functions on corneal epithelium in vitro and in vivo.●METHODS:In vitro the human corneal epithelial(HCE)cells were treated with serum free DMEM-F12 basic media containing 0,50,100,200,300,500,800,and 1000 ng/mL of netrin-1,respectively.The cells viability was detected by cell counting kit-8(CCK-8).The wound-healing assay was applied to assess the migration proficiency of HCE cells.Flow cytometry was used to analyze the cell-cycle distribution and apoptosis.In vivo,normal c57(6 wk)mice were demarcated with a trephine in the middle of the cornea to produce a 3-mm circular wound.Mice corneas were inflicted no epithelium with a 3-mm wound displayed,but remained the limbal epithelium intact.A blunt scalpel blade was used to remove the corneal epithelian cells,followed by topical netrin-1 application(200 ng/mL),and the group treated by PBS as control.The treated group was injected netrin-1 into the normal c57 mice inferior subconjunctival 4 h before trauma.Mouse corneal inflammation and neovascularization were observed under slit lamp microscope.The apoptosis of corneal cells was determined by TUNEL staining.●RESLUTS:A concentration of 200 ng/mL netrin-1 enhanced 25%of the HCE viability.The relative migration rates were 76.3%and 100%in control and netrin-1 treated group after cultured 72 h.Treated with netrin-1(200 ng/mL)decreased the apoptosis of HCE cells,as well as decreased their percentage from 19.3%±0.57%to 12.7%±0.42%of the total.The remaining wound area was 1.22 mm2 in control group but 0.22 mm2 in the netrin-1 treated group.Exogenous Netrin-1 inhibits apoptosis of corneal epithelial cells of c57 mice.TUNEL-positive cells at the epithelial layer of the corneas of the control and netrin-1 treated c57 mice at 24 h after wounding were 43.3%and 16.7%respectively.●CONCLUSION:Netrin-1 can reduce HCE apoptosis as well as promote its proliferation and migration.Topical application of netrin-1 promotes the injuryed cornea epithelial wound repair and inhibits apoptosis of corneal epithelial cells.These findings may offer potential therapies to repair the defects of corneal epithelial based on netrin-1.

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.

Guidelines for the application of artificial intelligence in the diagnosis of anterior segment diseases(2023)

The landscape of ophthalmology has obser ved monumental shifts with the advent of artificial intelligence(AI)technologies.This article is devoted to elaborating on the nuanced application of AI in the diagnostic realm of anterior segment eye diseases,an area ripe with potential yet complex in its imaging characteristics.Historically,AI’s entrenchment in ophthalmology was predominantly rooted in the posterior segment.However,the evolution of machine learning paradigms,particularly with the advent of deep learning methodologies,has reframed the focus.When combined with the exponential surge in available electronic image data pertaining to the anterior segment,AI’s role in diagnosing corneal,conjunctival,lens,and eyelid pathologies has been solidified and has emerged from the realm of theoretical to practical.In light of this transformative potential,collaborations between the Ophthalmic Imaging and Intelligent Medicine Subcommittee of the China Medical Education Association and the Ophthalmology Committee of the International Translational Medicine Association have been instrumental.These eminent bodies mobilized a consortium of experts to dissect and assimilate advancements from both national and international quarters.Their mandate was not limited to AI’s application in anterior segment pathologies like the cornea,conjunctiva,lens,and eyelids,but also ventured into deciphering the existing impediments and envisioning future trajectories.After iterative deliberations,the consensus synthesized herein serves as a touchstone,assisting ophthalmologists in optimally integrating AI into their diagnostic decisions and bolstering clinical research.Through this guideline,we aspire to offer a comprehensive framework,ensuring that clinical decisions are not merely informed but transformed by AI.By building upon existing literature yet maintaining the highest standards of originality,this document stands as a testament to both innovation and academic integrity,in line with the ethos of renowned journals such as Ophthalmology.

Therapeutic effects of topical netrin-4 in a corneal acute inflammatory model

AIM: To evaluate the therapeutic effect of netrin-4 on the early acute phase of inflammation in the alkali-burned eye.METHODS: Eye drops containing netrin-4 or phosphate buffered saline(PBS) were administered to a alkali-burn-induced corneal acute inflammatory model four times daily. The clinical evaluations, including fluorescein staining and inflammatory index, were performed on day 1, 4 and 7 using slit lamp microscopy.Global specimens were collected on day 7 and processed for immunofluorescent staining. The levels of inflammatory mediators in the corneas were determined by real-time polymerase chain reaction(PCR).RESULTS: Exogenous netrin-4 administered on rat ocular surfaces showed more improvements in decreasing fluorescein staining on day 4 and 7, and resolved alkali burn-induced corneal inflammation index on day 7(P 【0.01). The levels of IL-1β, IL-6, intercellular cell adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), monocyte chemotactic protein-1(MCP-1) and macrophage inflammatory protein-1(MIP-1) in corneas were decreased in netrin-4-treated groups(P 【0.05). In addition, netrin-4 significantly reduced the expression of leukocyte common antigen 45(CD45) in the alkali-burn cornea(P 【0.001).CONCLUSION: Topical netrin-4 accelerated wound healing and reduced the inflammation on alkali-burn rat model, suggesting a potential as an anti-inflammatory agent in the clinical to treat the acute inflammation.