Current Eye Research最新文献

{"title":"Association of Serum Levels of Ghrelin and NLRP3 with Diabetic Retinopathy.","authors":"Xin Lu, Min Wang, Mei Yan, Hao Liu, Xiabo Li, Xuejing Zheng, Menghan Xu, Rong Li, Lihua Hou","doi":"10.1080/02713683.2026.2682882","DOIUrl":"10.1080/02713683.2026.2682882","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the serum levels of ghrelin and Nod-like receptor protein 3 (NLRP3) in patients with diabetic retinopathy (DR) and evaluate their correlation with DR progression.</p><p><strong>Methods: </strong>Thirty-seven patients with DR admitted to the First People's Hospital of Xianyang between April 2024 and April 2025 were enrolled and classified into non-proliferative DR (NPDR) and proliferative DR (PDR) subgroups based on fundus lesion severity. Fifty-three patients with simple cataracts served as controls. Serum levels of ghrelin and NLRP3 were measured using enzyme-linked immunosorbent assay, and their relationship with systemic indicators was analyzed.</p><p><strong>Results: </strong>Serum ghrelin and NLRP3 levels differed significantly between the PDR, NPDR, and control groups (<i>p</i> < 0.001). Pairwise comparisons revealed statistically significant differences in serum ghrelin levels between the PDR and control groups, as well as between the NPDR and control groups (both <i>p</i> < 0.017). Serum NLRP3 levels differed significantly between the PDR and control, the PDR and NPDR, and the NPDR and control groups (all <i>p</i> < 0.017). Serum ghrelin levels were positively correlated with high-density lipoprotein levels (<i>r</i> = 0.325, <i>p</i> < 0.05) and the use of statin lipid-lowering drugs (<i>r_s</i> = -0.397, <i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Decreased serum ghrelin and elevated serum NLRP3 levels in patients with DR suggest that ghrelin and NLRP3 are involved in DR pathogenesis.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1123-1130"},"PeriodicalIF":1.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subclinical Corneal Neuropathy in Dry Eye Disease: A Driver of Ocular Surface Dysfunction?","authors":"Elio Almaoui, David J Calkins, Lauren K Wareham","doi":"10.1080/02713683.2026.2664593","DOIUrl":"10.1080/02713683.2026.2664593","url":null,"abstract":"<p><p>Dry eye disease (DED) is a prevalent ocular surface disorder traditionally attributed to tear film instability, inflammation, and loss of ocular surface homeostasis. Despite advances in anti-inflammatory therapies and a more sophisticated understanding of pathophysiology, response to treatment is often poor and inconsistent, suggesting additional underlying mechanisms are at play. Here we explore a possible primary role of neuropathy in driving the pathogenesis of DED. Corneal nerves provide afferent feedback through the sensory ophthalmic branch of the trigeminal nerve. This information generates an efferent output through motor nerves, parasympathetic nerves of cranial nerve VII, and the sympathetic nerves of the superior cervical ganglion. Disturbances to this circuit lead to tear film dysfunction, loss of homeostasis, corneal epithelial cell and ECM degradation, which may perpetuate a cycle of degeneration. Recognizing DED as a subclinical neuropathy may guide the development of novel therapeutic strategies focused on restoring corneal nerve integrity, extracellular matrix stability, and epithelial homeostasis.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1044-1055"},"PeriodicalIF":1.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could Retinal and Optic Nerve Microcirculation Serve as Biomarkers for Dyslexia?","authors":"Şule Barman Kakil, Seda Aybüke Sarı, Leyla Hazar","doi":"10.1080/02713683.2026.2667330","DOIUrl":"10.1080/02713683.2026.2667330","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate retinal and optic nerve head microcirculation in children with dyslexia using optical coherence tomography angiography (OCTA) and to explore whether retinal microvascular parameters differ between dyslexic and typically developing children.</p><p><strong>Methods: </strong>In this prospective cross-sectional study, thirty children with clinically diagnosed dyslexia and thirty age- and sex-matched healthy controls underwent OCTA imaging using the RTVue XR Avanti system. Parameters assessed included vessel density in the superficial and deep capillary plexuses (SCP, DCP), outer retinal and choriocapillaris flow areas, foveal avascular zone (FAZ) size, optic disk vascular metrics, and peripapillary retinal nerve fiber layer (RNFL) thickness. Axial length was also measured to account for anatomical variability. Group comparisons and effect size analyses were performed, and correlations between axial length and OCTA metrics were examined.</p><p><strong>Results: </strong>Children with dyslexia demonstrated significantly reduced vessel density in the DCP (<i>p</i> = 0.014), outer retinal flow area (<i>p</i> = 0.026), and peripapillary region (<i>p</i> < 0.001), while SCP and FAZ parameters were preserved. Temporal RNFL thickness was selectively decreased (<i>p</i> = 0.045). Axial length was comparable between groups (<i>p</i> = 0.064) and showed no significant correlation with microvascular parameters. Cohen's d values indicated the strongest effect size for peripapillary vessel density (<i>d</i> = 1.14).</p><p><strong>Conclusions: </strong>Children with dyslexia showed selective differences in retinal and optic nerve head microvascular parameters, particularly within deeper retinal layers and the peripapillary region. Given the cross-sectional design and modest sample size, these findings should be interpreted as exploratory and hypothesis-generating. Larger, longitudinal, and multimodal studies are required to confirm these observations and to clarify their potential research relevance.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1131-1138"},"PeriodicalIF":1.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effect of Oral Pemafibrate with Suppression of p-ULK1 Elevation in a Rat Ocular Hypertension-Induced Glaucoma Model.","authors":"Naoki Fujita, Ibuki Arizono, Chihiro Tsukahara, Mizuki Otsubo, Kana Sase, Yasushi Kitaoka","doi":"10.1080/02713683.2026.2723680","DOIUrl":"https://doi.org/10.1080/02713683.2026.2723680","url":null,"abstract":"<p><strong>Purpose: </strong>Pemafibrate was developed as a selective modulator of peroxisome proliferator-activated receptor alpha and is used as a treatment for hyperlipidemia. Although recent studies have shown a variety of functions <i>in vivo</i>, its effects on optic nerve axons remain unclear. The purpose of this study was to investigate the effects of oral administration of pemafibrate in a rat model of ocular hypertension glaucoma and to address its molecular mechanisms.</p><p><strong>Methods: </strong>Laser irradiation was used to create the rat model of ocular hypertension glaucoma. Pemafibrate was administered daily, and retinal nerve fibers were quantified, and optic nerve axon numbers were quantified after 3 weeks. Western blotting was performed to measure the expression of p-ULK1 Ser757.</p><p><strong>Results: </strong>Pemafibrate significantly inhibited axonal loss in the hypertensive glaucoma model, as well as loss of retinal nerve fibers in the peripheral area. Western blot analysis revealed an increase in p-ULK1 Ser757 in the retina of the hypertensive glaucoma model, which was significantly suppressed in the pemafibrate-treated group.</p><p><strong>Conclusions: </strong>These results suggest that pemafibrate may have neuroprotective effects associated with suppression of OHT-induced p-ULK1 Ser757 elevation. Because autophagic flux was not directly measured, the present findings suggest a possible modulatory role in autophagy-related signaling rather than demonstrating restoration of autophagy function.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1-8"},"PeriodicalIF":1.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Principal Component Analysis-Derived Optical Coherence Tomography Angiography Microvascular Metrics with Mild Cognitive Impairment in Patients with Non-Proliferative Diabetic Retinopathy: A Cross-Sectional Study.","authors":"Yihao Xia, Mengqi Wang, Jialing Dong, Hua Bai, Shirui Yang, Hejiang Ye","doi":"10.1080/02713683.2026.2717821","DOIUrl":"https://doi.org/10.1080/02713683.2026.2717821","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the association between principal component analysis (PCA)-derived optical coherence tomography angiography (OCTA) microvascular metrics and mild cognitive impairment (MCI) in patients with non-proliferative diabetic retinopathy (NPDR).</p><p><strong>Methods: </strong>This cross-sectional study included patients with mild to moderate NPDR who underwent cognitive assessment and macular spectral-domain OCTA imaging. Cognitive status was assessed using the Chinese version of the Montreal Cognitive Assessment-Basic. En face OCTA images of the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were analyzed using an OCTAVA-based standardized image-processing workflow. OCTA vascular parameters, foveal avascular zone morphology, and lacunarity were extracted for each plexus. Generalized estimating equation models were used to account for inter-eye correlation. PCA was performed separately for each vascular plexus to reduce redundancy among correlated OCTA parameters and generate layer-specific composite scores.</p><p><strong>Results: </strong>A total of 50 participants with mild or moderate NPDR (86 eyes) were included in the final analysis, including 26 participants (46 eyes) in the non-MCI group and 24 participants (40 eyes) in the MCI group. PCA identified a dominant shared variation pattern in each vascular plexus. PC1 explained 50.23%, 52.12%, and 56.92% of the total variance in the SVP, ICP, and DCP, respectively. After directional alignment, higher PC1-derived scores indicated greater OCTA-derived microvascular impairment. In adjusted logistic GEE models, higher PC1-derived scores were significantly associated with increased odds of MCI across vascular plexuses. Repeated random-split ROC analysis showed moderate discriminatory performance for unadjusted PC1-derived scores; however, after adjustment for covariates, the AUCs decreased to below 0.60. Adding PC2 and PC3 did not provide consistent incremental improvement.</p><p><strong>Conclusion: </strong>PCA-derived OCTA metrics may provide an interpretable approach for summarizing correlated vascular parameters and characterizing integrated microvascular alteration patterns related to MCI in NPDR. However, their limited adjusted discrimination requires further validation.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1-13"},"PeriodicalIF":1.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated Versus Image-Guided Cyclotorsion Control in FS-LASIK: A Vector Analysis Study.","authors":"Husna Topcu, Mevlut Celal Ocal, Mehmet Altun, Ugur Tunc, Dilek Yasa, Gonul Karatas Durusoy, Atilla Hacıbekiroglu, Bulent Kose","doi":"10.1080/02713683.2026.2718678","DOIUrl":"https://doi.org/10.1080/02713683.2026.2718678","url":null,"abstract":"<p><strong>Purpose: </strong>To compare automated cyclotorsion compensation using the WaveLight^® Topolyzer^™ system with manual cyclotorsion alignment guided by the Callisto image-guided system in achieving accurate astigmatic correction during femtosecond laser-assisted <i>in situ</i> keratomileusis (FS-LASIK).</p><p><strong>Methods: </strong>This retrospective, single-center study analyzed data from 159 eyes that underwent FS-LASIK with a 6-month postoperative follow-up. Group 1 (<i>n</i> = 113) received real-time automated cyclotorsion compensation using the WaveLight^® Topolyzer^™ system, whereas Group 2 (<i>n</i> = 46) underwent manual cyclotorsion alignment guided by the Callisto image-guided system when automated registration was not feasible. Postoperative uncorrected (UDVA) and corrected (CDVA) distance visual acuity, residual refractive astigmatism, and vector analysis parameters-including target-induced astigmatism (TIA), surgically induced astigmatism (SIA), correction index (CI), difference vector (DV), and index of success (IOS)-were evaluated at 1 and 6 months.</p><p><strong>Results: </strong>Baseline cylindrical refractive error was comparable between the groups (<i>p</i> = 0.661). At 6 months, mean residual astigmatism was -0.28 ± 0.26 D in Group 1 and -0.19 ± 0.22 D in Group 2, although the between-group difference did not reach statistical significance (<i>p</i> = 0.051). Group 2 achieved significantly better UDVA at 6 months (0.01 ± 0.02 logMAR) compared with Group 1 (0.04 ± 0.07 logMAR; <i>p</i> = 0.019). Vector analysis demonstrated a lower difference vector and a slightly higher correction index in Group 2, indicating more precise long-term astigmatic alignment.</p><p><strong>Conclusions: </strong>Both automated and image-guided cyclotorsion control strategies produced excellent visual and refractive outcomes after FS-LASIK. However, image-guided manual alignment using the Callisto system was associated with superior uncorrected visual acuity and a more favorable vector profile, supporting its use as an effective alternative when automated cyclotorsion registration is limited.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1-7"},"PeriodicalIF":1.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Intrinsically Photosensitive Retinal Ganglion Cells Ablation Regulates Myopia Development Through the Choroid/MAPK Pathway.","authors":"Ruotong Ouyang, Xiao Fan, Xiaochen Wang, Sisi Tan, Miao Wei, Yujia Huo, Hong Li","doi":"10.1080/02713683.2026.2715205","DOIUrl":"https://doi.org/10.1080/02713683.2026.2715205","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the role of selective ablation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in regulating axial length (AL) and scleral remodeling during myopia progression.</p><p><strong>Methods: </strong>Three-week-old pigmented guinea pigs were randomly assigned to five experimental groups, with form-deprivation myopia (FDM) models receiving intravitreal melanopsin-saporin (MEL-SAP) injections. Molecular analyses (Western blot, RT-qPCR) quantified expression of retina-, choroid-, and sclera-related factors. Structural changes were assessed <i>via</i> immunohistochemistry, optical coherence tomography (OCT; choroidal/scleral thickness), and Masson's trichrome staining (scleral collagen organization).</p><p><strong>Results: </strong>In FDM models, melanopsin expression was elevated. MEL-SAP injection shortened the AL and slowed the progression of late-stage myopia. This treatment attenuated AL elongation and delayed refractive progression in FDM+MEL-SAP groups versus FDM alone. Molecular analyses indicated suppression of FDM-induced scleral remodeling markers and choroidal hypoxia indicators following selective ipRGCs ablation. Activation of extracellular regulated kinase (ERK) by the specific agonist Ro67-7476 reversed the effects of ipRGC ablation, demonstrating the functional involvement of microtubule-associated protein kinase (MAPK)/ERK signaling in mediating the anti-myopic effects. Choroidal perfusion experiments supported selective ipRGC ablation's primary action through the retinal-choroidal-scleral(RCS) axis.</p><p><strong>Conclusion: </strong>Collectively, our results reveal that the ipRGCs mediates the effects of choroid/MAPK pathway on AL, providing a refined understanding of retinal mechanisms and identifying a potential therapeutic target for myopia.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1-13"},"PeriodicalIF":1.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tear GDF15 Levels Are Elevated in Primary Open-Angle Glaucoma Patients and Correlate With Aqueous Humor Levels.","authors":"Cory N Sharp, Kenta Kato, Andrea Santeford, Erin Sieck, Arsham Sheybani, Mitsukuni Yoshida, Rajendra S Apte","doi":"10.1080/02713683.2026.2718679","DOIUrl":"https://doi.org/10.1080/02713683.2026.2718679","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether growth differentiation factor 15 (GDF15) is detectable and elevated in tears of patients with primary open-angle glaucoma (POAG) and whether tear GDF15 levels correlate with aqueous humor (AH) GDF15 levels.</p><p><strong>Methods: </strong>In a single-center cross-sectional study, we recruited 21 patients undergoing ocular surgery, including patients with moderate to severe POAG undergoing glaucoma or cataract surgery (<i>n</i> = 11) and controls without glaucoma undergoing cataract surgery (<i>n</i> = 10). Demographic data were obtained by chart review. Tear samples were obtained preoperatively using Schirmer strips, and AH samples were obtained from the initial limbal paracentesis during surgery. GDF15 concentrations were quantified using enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>AH GDF15 levels were significantly elevated in POAG samples compared with controls (<i>p</i> = .0057), and this difference remained significant after normalization to total protein (<i>p</i> = .0193). GDF15 was detectable in nearly all tear samples and was significantly higher in POAG patients than in controls (<i>p</i> = .0003), remaining significant after normalization (<i>p</i> = .0022). Raw tear and AH GDF15 levels were not significantly correlated (<i>p</i> = .0736, <i>R</i>² = 0.1588) but showed significant positive correlation after normalizing to total protein and removing two outliers (<i>p</i> = .0019, <i>R</i>² = 0.4416).</p><p><strong>Conclusion: </strong>Tear GDF15 is detectable and significantly elevated in POAG patients. Tear GDF15 correlates with AH GDF15 after normalization to total protein. These findings suggest the potential of tear GDF15 as a noninvasive molecular biomarker of POAG and highlight the importance of larger studies to validate these findings.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1-5"},"PeriodicalIF":1.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginkgo Biloba Standardized Extract EGb 761 Reduces Light and Toxin-Induced Photoreceptor Cell Damage via Regulating Oxidative Stress and Autophagy.","authors":"Qiufeng Teng, Maryam Chudhary, Wenkang Dong, Yang Yu, Yulang Meng, Jinjuan Lv, Siyang Liu, Bing Wang, Xiang Ren","doi":"10.1080/02713683.2026.2715153","DOIUrl":"10.1080/02713683.2026.2715153","url":null,"abstract":"<p><strong>Purpose: </strong>Retinal degeneration (RD) is the common ocular pathogenesis characterized by photoreceptor cell dysfunction. Increasing evidence has shown that the accumulation of 4-hydroxynonenal (4-HNE) is closely associated with RD. <i>Ginkgo biloba</i> special extract EGb 761 has been widely used to prevent and treat certain diseases. In this study, we investigated the effect of EGb 761 on photoreceptor cell damage in retinal degeneration and related mechanism.</p><p><strong>Methods: </strong><i>Balb/c</i> mice and 661w cells were used <i>in vivo</i> and <i>in vitro</i>. CCK8 was used to measure the cell viability after 4-HNE or EGb 761 treatment. Apoptosis was evaluated by TUNEL staining. Related gene expression was measured by qRT-PCR and Western blot. Autophagy was observed by TEM and autophagy flux. ROS production was measured using the DCFH-DA probe.</p><p><strong>Results: </strong>Electroretinography and H&E staining showed that retinal function and morphology were impaired and the expression of LC3 and p62 was decreased or increased and the expressions of anti-oxidative stress-related genes Trx1, Sod2 and Glrx1 were reduced after light damage, EGb 761 treatment ameliorated these processes. After 4-HNE treatment <i>in vitro</i>, the fraction of apoptotic cells was increased and the expression of Bax was increased and Bcl2 was decreased. ROS generation was increased and the expression of Sod2 and Glrx1 was reduced. Furthermore, autophagy was dysregulated, the expression of p62 was increased, and the LC3II/LC3I level was decreased. TEM and autophagic flux showed that autophagosomes accumulated. EGb 761 treatment alleviated these impairments. However, apoptotic cells increased significantly, ROS generation increased and the expression of p-AMPK, p-ERK and Nrf2 was decreased after AMPK inhibitor Compound C treatment, compared with 4-HNE and EGb 761 alone treatment groups.</p><p><strong>Conclusion: </strong>EGb 761 exerts a protective effect on photoreceptor cell damage in retinal degeneration. This process was associated with a modification of the AMPK/ERK signaling pathway that regulates oxidative stress and autophagy.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1-13"},"PeriodicalIF":1.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2i Canagliflozin Exerts Neuroprotection in Diabetic Retinopathy by Inhibiting Microglial Proinflammatory Cytokine Release by Downregulating the TLR4/NF-κB/NLRP3 Pathway.","authors":"Tai Guo, Yue Liu, Mengxia He, Yuling Lian, Xiyu Wu, Hanpeng Zhao, Xiaohong Chen, Zhixin Mo, Yuman Li, Mingsi Chi, Xiaofeng Huang, Dejia Fang, Qianli Meng, Shangli Jin, Ning Hou, Ying Cui","doi":"10.1080/02713683.2026.2714720","DOIUrl":"https://doi.org/10.1080/02713683.2026.2714720","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic retinopathy (DR) is the leading cause of preventable blindness among working-age adults. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), first-line treatments for diabetes mellitus (DM), have demonstrated efficacy in decelerating DR progression. However, the mechanisms remain unclear. This study investigates how canagliflozin (CANA), an SGLT2 inhibitor, exerts neuroprotective effects in DR by suppressing microglial proinflammatory cytokine release.</p><p><strong>Materials and methods: </strong>Using high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice and BV-2 microglial cells under high glucose (HG) conditions, we elucidate the mechanistic link between CANA and neuroinflammation suppression in DR. Retinal structure and function were assessed using optical coherence tomography and electroretinography. Protein was evaluated <i>via</i> Western blotting, immunostaining, and enzyme-linked immunosorbent assay. Cell viability was measured using the Cell Counting Kit-8 assay.</p><p><strong>Results: </strong>CANA demonstrated significant neuroprotective effects in diabetic retinopathy (DR) by attenuating microglia-mediated neuroinflammation. In HFD and STZ-induced diabetic mice, the ganglion cell complex thickness and a-wave and b-wave amplitudes decreased (<i>p</i> < 0.05). CANA upregulated the ganglion cell complex thickness (<i>p</i> < 0.05) and TSPO expression (<i>p</i> < 0.05), and tended to increase a-wave and b-wave amplitudes (<i>p</i> > 0.05) in retinas in DM mice. In BV-2 cells, HG activated BV-2 cells, downregulated TSPO expression, and promoted proinflammatory cytokine release, toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression, and nuclear translocation of p65 and phosphorylated p65 (<i>p</i> < 0.05). CANA reduced BV-2 cell viability, upregulated TSPO, while suppressing proinflammatory cytokine release, TLR4 and NLRP3 expression, and nuclear translocation of p65 and phosphorylated p65 (<i>p</i> < 0.05). Notably, CANA inhibited the TLR4/NF-κB/NLRP3 pathway, evidenced by reduced TLR4/NLRP3 protein levels and diminished nuclear translocation of p65 and phosphorylated p65 in microglia.</p><p><strong>Conclusions: </strong>These findings identify CANA as a promising therapeutic candidate for DR, acting through TLR4/NF-κB/NLRP3-dependent modulation of microglial activation.</p>","PeriodicalId":10782,"journal":{"name":"Current Eye Research","volume":" ","pages":"1-13"},"PeriodicalIF":1.7,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}