PURPOSE:To describe a modified scleral fixation technique for a four-haptic foldable intraocular lens using 10-0 looped polypropylene sutures, aimed at reducing suture exposure risks and enhancing centration stability in eyes with inadequate capsular support. METHODS:This retrospective interventional study included nine eyes of nine patients, who underwent modified scleral fixation of a four-haptic foldable intraocular lens between January 2023 and January 2024. RESULTS:Over a mean follow-up period of 10.89 months, postoperative logarithm of the minimum angle of resolution best-corrected visual acuity improved significantly (20/43 vs. 20/130 preoperatively). The mean intraocular lens tilt was 0.27 ± 0.09 µ m, with acceptable endothelial cell loss (9.96%). No intraoperative or postoperative complications were observed. CONCLUSION:This technique performed through a small incision, achieves reliable intraocular lens positioning and visual improvement via four-point fixation while effectively eliminating suture-related complications.

Purpose:Wet age-related macular degeneration is a leading cause of irreversible vision loss, primarily due to choroidal neovascularization (CNV) and subsequent fibrosis. Although current anti-vascular endothelial growth factor A (anti-VEGF) therapies offer significant benefits, many patients exhibit limited or no response and develop drug resistance over time, necessitating the exploration of complementary or alternative therapeutics. This study aimed to identify and characterize a platelet-derived growth factor-C (PDGF-C)-targeting DNA aptamer and to evaluate its therapeutic potential for suppressing CNV and fibrosis, including in an anti-VEGF-refractory setting. Methods:A DNA aptamer against PDGF-C (α-PC aptamer) was identified using systematic evolution of ligands by exponential enrichment. Its binding to PDGF-C and inhibition of PDGF-C/platelet-derived growth factor receptor alpha (PDGFRα) interaction were assessed using surface plasmon resonance. The effects of the α-PC aptamer on PDGF-C-induced proliferation, migration, and PDGFRα, Akt, and extracellular-regulated kinase (ERK) signaling were examined in fibroblasts and human umbilical vein smooth muscle cells (HUVSMCs). In vivo efficacy was evaluated in a laser-induced CNV mouse model, including anti-VEGF refractory aged mice. Results:The α-PC aptamer specifically bound to PDGF-C and effectively blocked its binding to PDGFRα. The α-PC aptamer significantly inhibited PDGFRα, Akt, and ERK activation and suppressed PDGF-C-induced proliferation and migration of both fibroblasts and HUVSMCs. Importantly, in a laser-induced CNV mouse model, the α-PC aptamer markedly reduced neovascularization and fibrosis; it particularly retained efficacy in suppressing CNV in anti-VEGF refractory aged mice, where anti-VEGF treatment failed to do so. Conclusions:These findings suggest that the α-PC aptamer represents a promising therapeutic agent for treating neovascular diseases, especially in patients refractory to anti-VEGF treatment.

Diabetic retinopathy (DR) is a leading cause of visual impairment and blindness in industrialized countries, resulting from diabetes mellitus. Prostaglandin E2 (PGE2), synthesized by cyclooxygenases, contributes to inflammation and apoptosis via the E-prostanoid receptor 2 (EP2R). Our previous studies demonstrated that EP2R antagonists mitigate inflammation and microvascular dysfunction in streptozotocin (STZ)-induced DR. Given the paracrine role of extracellular vesicles (EVs) in DR, we hypothesized that EVs derived from human endothelial cells (ECs) may regulate the PGE2/EP2R pathway in DR. Using an STZ-induced diabetic mouse model, we administered intravitreal injections of AAV2-shEP2R and evaluated retinal histology, optical coherence tomography, and biochemical markers. EV morphology, size, and concentration from high glucose (HG)-treated ECs were analyzed. Small RNA expression in plasma EVs from DR patients was assessed via deep sequencing. EP2R inhibition via AAV2-mediated knockdown significantly reduced retinal vascular leakage, leukostasis, and retinal Müller cell (rMC) activation. MiRNA profiling revealed elevated levels of miR-423-5p and miR-21-5p in EVs from HG-treated ECs, which were suppressed in EVs from EP2R antagonist-treated cells. Notably, deep sequencing of plasma EVs from DR patients confirmed significant upregulation of these miRNAs compared to healthy controls. MiR-423-5p and miR-21-5p function as key paracrine mediators promoting Müller cell activation and retinal microvascular dysfunction in DR. These findings highlight the potential of circulating EVs as vehicles for miRNA-based therapeutic interventions in DR.

BACKGROUND Genome-wide association studies have been suggested single-nucleotide polymorphisms (SNPs) can influence susceptibility to high myopia (HM). To investigate the associations of multiple SNPs of 4 common genes and HM, we collected all related articles about these 4 common SNPs and risk of HM. MATERIAL AND METHODS PubMed and Wanfang databases were searched for articles published until Dec 10, 2025 using the keywords 'GJD2' or 'ZC3H11B' or 'MMP1' or 'MMP9', 'polymorphism' and 'myopia' or 'shortsightedness'. Odds ratios and 95% confidence intervals were used to examine the association between above 4 genes' SNPs and HM risk using Stata software. RESULTS We performed a meta-analysis of data from 15 published articles. There were 2 SNPs in the GJD2 gene, 4 SNPs in the ZC3H11B gene, 1 in SNP in the MMP1 gene, and 1 SNP in the MMP9 gene. After analyses using Stata, significant results were detected: rs3743123 in the GJD2 gene was associated with a decreased overall HM risk. Additionally, similar trends were detected in all 4 SNPs in the ZC3H11B gene: rs4373767, rs4428898, rs10779363and rs7544369. CONCLUSIONS Our results suggest that the GJD2 gene rs3743123 and ZC3H11B gene 4 SNPs (rs4373767, rs4428898, rs10779363, rs7544369) polymorphisms are associated with risk of HM. Our results need to be confirmed by larger studies and mechanism research, which may aid in the early identification and prognostic evaluation of HM.

Diabetic retinopathy (DR) is a leading cause of vision loss in working-age adults and often progresses to proliferative diabetic retinopathy (PDR) with irreversible complications. Anti-vascular endothelial growth factor (VEGF) therapy remains the first-line treatment; however, resistance poses a significant challenge, necessitating alternative therapeutic targets. This study explores the role of angiopoietin-like protein 4 (ANGPTL4) in PDR pathogenesis, emphasizing vascular-immune-lymphatic interactions. We found significantly elevated ANGPTL4 and VEGF-C levels in the vitreous humor of patients with PDR, which were not affected by anti-VEGF therapy. In vivo, full-length ANGPTL4 and its C-terminal fragment promoted pathological angiogenesis and lymphatic-like remodeling in diabetic murine retinas, characterized by increased lymphatic vessel endothelial hyaluronan receptor 1, prospero homeobox 1, and VEGF receptor 3 (VEGFR3) expression. Single-cell sequencing further revealed ANGPTL4-driven immune dysregulation, with abnormal infiltration of CD4+ T cells and dendritic cells. Knockdown of ANGPTL4 in mice with oxygen-induced retinopathy alleviated retinal hypoxia, neovascularization, and vascular leakage. Mechanistically, retinal hypoxia markedly increased ANGPTL4 expression levels in the retina, which activated the activator protein-1 (AP-1) transcription factor complex and promoted Cd83 transcription in mouse heart microvascular endothelial cells. Additionally, ANGPTL4 bound to neuropilin-1 (NRP1)/VEGFR3, driving human lymphatic endothelial cell proliferation and lymphatic vessel ingrowth from the optic nerve sheath into the retina, a finding that suggests a novel pathway independent of angiopoietin-Tie signaling. These findings establish ANGPTL4 as a key mediator of immune-vascular interactions in PDR and a potential therapeutic target to address both pathological angiogenesis and lymphatic dysfunction. ARTICLE HIGHLIGHTS:Some patients with proliferative diabetic retinopathy (PDR) have poor responses to anti-vascular endothelial growth factor (anti-VEGF) therapy. This situation highlights the need for additional therapeutic approaches. In proliferative diabetic retinopathy, what is the role of ANGPTL4 that differs from VEGF? We found that ANGPTL4 is elevated in the vitreous humor of patients with PDR who are poorly responsive to anti-VEGF therapy. ANGPTL4, particularly its C-terminal fragment, causes retinal lymphatic-like remodeling in diabetic mice. This study provides novel insights into the complex interplay between immune activation, neovascularization, and lymphatic-like remodeling in PDR. Our findings deepen our understanding of PDR pathophysiology and propose a promising therapeutic target.

Age-related macular degeneration involves the gradual degeneration of retinal pigment epithelium (RPE) cells. A better understanding of the molecular mechanism underlying RPE impairment is beneficial to the treatment of AMD. Here, we identify VDAC1 oligomerization as a critical initiator of RPE cell degeneration and death in AMD development. Using in vitro and in vivo models, we demonstrate that VDAC1 forms oligomers that promote mitochondrial membrane permeabilization and facilitates the leakage of mitochondrial DNA (mtDNA). Cytosolic mtDNA serves as a potent stimulator of cGAS-STING pathway. Strikingly, we find that STING activation promotes assembly of the PANoptosome complex, which integrates components of pyroptosis (NLRP3), apoptosis (Caspase-8), and necroptosis (RIPK3). Pharmacological inhibition of either VDAC1 oligomerization or STING activation preserves mitochondrial integrity, suppresses mtDNA release, inhibits PANoptosis, and restores RPE function. Blockade of the VDAC1-mtDNA-STING-PANoptosis axis alleviates RPE atrophy, retinal thinning, and AMD-like ocular pathologies in a sodium iodate-induced AMD mouse model. Going further, we show that O-GlcNAcylation of VDAC1 at threonine 165 (T165) promotes its oligomerization and accelerates disease progression. Mutation of T165 diminishes O-GlcNAc modification, reduces VDAC1 oligomer formation, and inhibits subsequent activation of cGAS-STING signaling and PANoptosis. Together, our findings uncover a mechanism by which VDAC1 oligomerization-mediated activation of PANoptosis during AMD. This work identifies VDAC1 oligomerization and its regulatory O-GlcNAcylation as promising targets for therapeutic intervention and provides mechanistic insights into how mitochondrial stress links innate immunity and inflammatory cell death in retinal degenerative disease.

Diabetic retinopathy (DR) is a major cause of vision loss in working-age adults with diabetes. Increasing evidence implicates neuroinflammation as a vital element in the disease process of DR, yet the molecular mechanisms by which neuroinflammation activation occurs are not fully understood. This study shows that elevated glucose levels enhance O-GlcNAcylation of voltage-dependent anion channel 1 (VDAC1) at threonine 165. This modification promotes VDAC1 oligomerization, facilitating cytosolic translocation of mtDNA. The cytosolic mtDNA activates Z-DNA binding protein 1, leading to its activation and subsequent inflammatory responses. Importantly, mtDNA levels in the vitreous fluid of patients with DR were higher, and mtDNA levels were positively correlated with the retinal thickness and negatively correlated with visual acuity. Taken together, our findings reveal a hyperglycemia-driven signaling axis in Müller cells that couples metabolic dysregulation with neuroinflammation, offering mechanistic insights and therapeutic opportunities for DR. Article Highlights The limited efficacy of anti-VEGF therapy in diabetic retinopathy (DR) highlights the importance of nonvascular mechanisms in disease progression. Hyperglycemia is a key driver of neuroinflammation in DR. Hyperglycemia results in VDAC1 O-GlcNAcylation in Müller glia, leading to mtDNA release and ZBP1 activation, thereby linking metabolic stress to neuroinflammation in DR. Targeting VDAC1-mediated mtDNA release or using vitreous mtDNA as a biomarker may enable earlier diagnosis and novel therapeutic strategies for DR.

Nonexudative age-related macular degeneration (dry AMD) is characterized by the progressive degeneration of retinal pigment epithelial (RPE) cells and photoreceptors, resulting in central vision loss. The disease is primarily marked by the accumulation of drusen and RPE atrophy. Given the emerging role of miR-21-5p in various ocular diseases, including diabetic retinopathy, glaucoma, pterygium, and choroidal neovascularization, we hypothesized that miR-21-5p may also impact RPE cell integrity in AMD. To test this hypothesis, we employed a rat model of dry AMD induced by sodium iodate (NaIO3) and evaluated the effects of miR-21-5p modulation via intravitreal injections of miR-21-5p agomir or antagomir. Comprehensive assessments were performed using optical coherence tomography (OCT), fundus imaging, histopathology, and biochemical markers. Our results demonstrated an upregulation of miR-21-5p in response to NaIO3 treatment. Administration of miR-21-5p agomir exacerbated RPE damage, while pretreatment with miR-21-5p antagomir mitigated these detrimental effects. Furthermore, in vitro experiments revealed that miR-21-5p regulates necroptosis in CoCl2-treated RPE cells by targeting Pellino1 (Peli1) via its 3' untranslated region, thereby inhibiting Peli1 expression. Overexpression of Peli1 effectively counteracted the necroptotic effects induced by CoCl2. These findings highlight the potential of miR-21-5p as a therapeutic target in dry AMD, expanding our understanding of miRNA-mediated regulation of RPE cells and suggesting new avenues for treatment strategies.

Age-related macular degeneration (AMD) is the leading cause of central vision impairment among the elderly. Geographic atrophy is a defining characteristic of AMD, but the detailed mechanism for massive loss of retinal pigment epithelium (RPE) cells is not fully understood. In this study, we found that Z-DNA binding protein 1 (ZBP1), a sensor for dsDNA, is able to induce RPE cell PANoptosis. Silencing ZBP1 efficiently alleviates RPE degeneration and AMD symptoms. Mechanistically, mitochondrial permeability transition pore (mPTP) opening stimulated by Ca2+ overload can trigger the releasing of mtDNA, which leads to ZBP1 activation and PANoptosis. Importantly, our findings reveal a significant role of aberrant formation of mitochondria-associated ER membranes (MAMs) in AMD. MAMs act as conduits for transferring Ca2+ from the ER to mitochondria through the VDAC1/GRP75/IP3R1 complex. Furthermore, our results indicate that GRP75 O-GlcNAcylation is involved in MAM formation. Genetic suppression of GRP75 attenuates PANoptosis and AMD progression. In summary, our study sheds light on the intricate organelle interplay underlying AMD and presents insights into potential avenues for AMD intervention.

Diabetic retinopathy (DR) is widely acknowledged as an ocular complication of diabetes mellitus involving retinal inflammation and secondary neuro/microvascular degeneration. Müller glial cells play a crucial role in regulating retinal homeostasis and neuroinflammation within the retina. Farnesoid X nuclear receptor (FXR) has emerged as a potential regulator of metabolic homeostasis and inflammatory responses as a bile acid nuclear receptor. However, its precise role in DR remains unclear. In order to investigate the effect of FXR on DR, we employed Sprague‐Dawley rats treated with streptozotocin (STZ) and human Müller glial cells treated with advanced glycation end products (AGEs) or high glucose with palmitate (HG + PA). Our investigations revealed downregulation of FXR in DR. Furthermore, we demonstrated that activating FXR could mitigate the progression of DR, with its protective effects linked to the inhibition of inflammatory responses within Müller cells. Mechanistically, FXR could ameliorate mitochondrial dysfunction and suppress the opening of the mitochondrial permeability transition pore. This action blocked the release of mitochondrial DNA (mtDNA) from the mitochondria into the cytoplasm, thereby inhibiting the abnormal activation of the cGAS/STING pathway in DR. Further studies revealed that FXR upregulates mitochondrial transcription factor A (TFAM) by modulating ATF4/NRF1, ultimately enhancing mitochondrial function. Knockdown of FXR reversed the above effects. Additionally, FXR activation effectively rescued mitochondrial dysfunction, as evidenced by Tunicamycin (TUN)‐mediated assays, further validating our findings. In summary, our findings suggest that targeting FXR may offer promising strategies for future therapeutic interventions in the treatment of DR.

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes mellitus (DM) and remains the leading cause of blindness among the working-age population. Neurodegeneration, microvascular dysfunction, gliosis, and neovascularization are key hallmarks of DR. Emerging evidence has highlighted the involvement of protein post-translational modifications (PTMs) in DR progression. PTMs, including glycosylation, phosphorylation, ubiquitination, methylation, and acetylation, regulate protein stability, localization, and activity in response to hyperglycemic stress and oxidative damage, thereby perturbing the function of retinal vascular endothelial cells, neurons, and glial cells. A systematic literature search was performed in PubMed for studies published up to June 2025, using a combination of the term "Diabetic retinopathy" with keywords related to post-translational modifications, including "glycosylation", "phosphorylation", "ubiquitination", "methylation", "acetylation", and "SUMOylation". Eligible studies were limited to English-language publications that specifically examined the interaction between PTMs and DR, including both original research and review articles. Studies were excluded if they only mentioned PTMs and DR without investigating the direct relationship between them. This review did not involve formal statistical analysis or meta-analytic techniques. In this review, we first outlined the physiological roles of PTMs in vascular leakage, neovascularization, reactive gliosis, and retinal neuronal degeneration during DR. Next, we examined the contributions and interplay of distinct PTM types in these pathological events. Lastly, we explored the potential of PTMs as biomarkers and therapeutic targets in DR. A deeper understanding of the role of PTMs in DR may provide novel mechanistic insights and facilitate early diagnosis and treatment of DR.

Age-related macular degeneration (AMD) is a common threat to vision among the elderly, which is marked by retinal pigment epithelium (RPE) degeneration and geographic atrophy. Progressive loss of RPE cells is a defining hallmark of dry AMD, and although ferroptosis has emerged as a key pathogenic mechanism, its upstream triggers remain poorly understood. Here, we identify an organelle crosstalk-based mechanism that drives ferroptosis in RPE. We demonstrate that glucose-regulated protein 75 (GRP75), a critical protein in forming mitochondria-associated endoplasmic reticulum membranes (MAMs), was an upstream signal modulator of ferroptosis in RPE cells. GRP75 expression was significantly upregulated in NaIO 3 -induced AMD models. Mechanistically, GRP75 upregulation enhanced calcium transfer from endoplasmic reticulum to mitochondria via the IP3R1-GRP75-VDAC1 complex, leading to mitochondrial Ca 2+ overload, triggering mitochondrial permeability transition pore (mPTP) opening, and subsequent mtDNA leakage. Released mtDNA activated the cGAS-STING signaling and lead to the recruitment and activation of TBK1. Subsequently, TBK1 phosphorylated p62/SQSTM1 and initiated GPX4 degradation via both autophagy-lysosome and ubiquitin-proteasome systems. As a key negative regulator of ferroptosis, GPX4 degradation markedly accelerates RPE cell ferroptosis and promotes AMD progression. Knockdown of GRP75 effectively preserved GPX4 stability, attenuated lipid peroxidation, and restored retinal neurodegeneration in vivo . These findings establish GRP75 as a central mediator in ferroptosis and define a new ferroptosis suppression mechanism which may represent new strategies for therapeutic intervention in AMD and other ferroptosis-associated diseases.

Purpose Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly individuals. Retinal pigment epithelium (RPE) ferroptosis is a significant pathogenetic component in AMD. This study aims to elucidate the role and mechanisms of fatty acid desaturase 1 (FADS1) in ferroptosis as well as AMD progression. Methods An integrated bioinformatics analysis based on the array of data from the GEO database was conducted to identify candidates involved in ferroptosis during AMD. Subsequently, cellular and mouse models of AMD were developed using sodium iodate (NaIO3) to confirm the altered expression of FADS1. After treatment with a FADS1 inhibitor, cell survival, lipid peroxidation, and indicators of AMD were assessed in vitro and in vivo models. Further, immunofluorescence, immunohistochemistry, and swept-source OCT imaging were performed to assess the impacts of pharmacological inhibition of transcription factor specificity protein 1 (Sp1) on FADS1 and ferroptosis. Results FADS1 expression was upregulated in AMD patients and in vitro and in vivo models of AMD. Its pharmacological inhibition had decreased mitochondrial ROS formation, lipid peroxidation, and ferroptosis as well as increased RPE cell function in ARPE-19 cells and C57BL/6J mouse models of AMD. Mechanistically, Sp1 was identified as a key transcription factor of FADS1. Moreover, Sp1 inhibition downregulated FADS1 expression consequently attenuating FADS1-mediated ferroptosis as well as AMD phenotypes. Conclusion For the first time, we demonstrated that Sp1 regulates FADS1-mediated ferroptosis in RPE cells. Our findings provide novel insights into the progression and treatment of AMD.

Proliferation and transdifferentiation of the retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy (PVR); however, the critical regulators of this process remain to be elucidated. Here, we investigated the role of tenascin-C in PVR development. In vitro, exposure of human ARPE-19 (hRPE) cells to TGF-β2 increased tenascin-C expression. Tenascin-C was shown to be involved in TGF-β2-induced transdifferentiation of hRPE cells, which was inhibited by pretreatment with tenascin-C siRNA. In PVR mouse models, a marked increase in the expression of tenascin-C mRNA and protein was observed. Additionally, immunofluorescence analysis demonstrated a dramatic increase in the colocalization of tenascin-C with RPE65 or α-smooth muscle actin(α-SMA) in the epiretinal membranes of patients with PVR. There was also abundant expression of integrin αV and β-catenin in the PVR membranes. ICG-001, a β-catenin inhibitor, efficiently attenuated PVR progression in a PVR animal model. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of PVR via the integrin αV and β-catenin pathways. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of epiretinal membrane development associated with PVR.

Cigarette smoke (CS) is an important indoor air pollutant associated with an increased risk of ocular surface disease. As the eye's outermost layer, the cornea is highly sensitive to air pollutants like CS. However, the specific mechanisms linking CS exposure to corneal dysfunction have not been fully elucidated. In the present study, we found that CS exposure damages corneal epithelial cells, accompanied by increased iron (Fe2+) levels and lipid peroxidation, both hallmarks of ferroptosis. Ferroptosis inhibitors, including Ferrostatin-1 (Fer-1) and Deferoxamine mesylate (DFO), protect against CS-induced cell damage. To understand the underlying mechanisms, we investigated how CS affects iron and lipid metabolism. Our results showed that CS could upregulate intracellular iron levels by increasing TFRC expression and promote lipid peroxidation by increasing ACSL4 expression. Silencing ACSL4 or TFRC expression prevented CS-induced ferroptosis. Furthermore, we found that the upregulation of TFRC and ACSL4 was driven by increased YAP transcription. Pharmacological or genetic inhibition of YAP effectively prevented corneal epithelial cell ferroptosis under CS stimulation. Additionally, our results suggest that CS exposure could increase O-GlcNAc transferase activity, leading to YAP O-GlcNAcylation. This glycosylation of YAP interfered with its K48-linked ubiquitination, resulting in YAP stabilization. Collectively, we found that CS exposure induces corneal epithelial cell ferroptosis via the YAP O-GlcNAcylation, and provide evidence that CS exposure is a strong risk factor for ocular surface disease.

A 73-year-old male patient was suffering from aphakia due to ocular trauma. Capsular implantation of a posterior chamber intraocular lens (PCIOL) was impossible in the absence of capsular support. Three-point transscleral suture fixation was used. The technique was performed under retrobulbar anesthesia. A three-looped haptics one-piece foldable PCIOL was suspended in the eye with one haptic at 6 o’clock and tied by a cow-hitch knot, and the haptics at 2 o’clock and 10 o’clock were threaded by another suture. The patient was followed up for 6 months postoperatively, and the postoperative logarithm of the minimum angle of resolution at the final follow-up was 0.3. The intraocular lens remained well positioned and stable. No complications, such as suture loosening, hypotony, chronic inflammation, or retinal detachment, were observed during the postsurgery follow-up period.

The intricate interaction network necessary for essential physiological functions underscores the interdependence among eukaryotic cells. Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs), specialized junctions between mitochondria and the ER, were recently discovered. These junctions participate in various cellular processes, including calcium level regulation, lipid metabolism, mitochondrial integrity maintenance, autophagy, and inflammatory responses via modulating the structure and molecular composition of various cellular components. Therefore, MAMs contribute to the pathophysiology of numerous ocular disorders, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD) and glaucoma. In addition to providing a concise overview of the architectural and functional aspects of MAMs, this review explores the key pathogenetic pathways involving MAMs in the development of several ocular disorders.

Background Thyroid-associated orbitopathy (TAO) is a disease associated with autoimmune thyroid disorders and it can lead to proptosis, diplopia, and vision-threatening compressive optic neuropathy. To comprehensively understand the molecular mechanisms underlying orbital adipogenesis in TAO, we characterize the intrinsic molecular properties of orbital adipose/connective tissue from patients with TAO and control individuals. Methods RNA sequencing analysis (RNA-seq) was performed to measure the gene expression of orbital adipose/connective tissues of TAO patients. Differentially expressed genes (DEGs) were detected and analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA). The protein–protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified by the Cytoscape plug-in, cytoHubba. We validated several top DEGs through quantitative real-time polymerase chain reaction (qRT–PCR). Results We identified 183 DEGs in adipose tissue between TAO patients (n = 3) and control patients (n = 3) through RNA sequencing, including 114 upregulated genes and 69 downregulated genes. The PPI network of these DEGs had 202 nodes and 743 edges. PCR-based validation results of orbital adipose tissue showed multiple top-ranked genes in TAO patients (n = 4) are immune and inflammatory response genes compared with the control individual (n = 4). They include ceruloplasmin isoform x3 (CP), alkaline tissue-nonspecific isozyme isoform x1 (ALPL), and angiotensinogen (AGT), which were overrepresented by 2.27- to 6.40-fold. Meanwhile, protein mab-21-like 1 (MAB21L1), phosphoinositide 3-kinase gamma-subunit (PIK3C2G), and clavesin-2 (CLVS2) decreased by 2.6% to 32.8%. R-spondin 1 (RSPO1), which is related to oogonia differentiation and developmental angiogenesis, was significantly downregulated in the orbital muscle tissues of patients with TAO compared with the control groups (P = 0.024). Conclusions Our results suggest that there are genetic differences in orbital adipose-connective tissues derived from TAO patients. The upregulation of the inflammatory response in orbital fat of TAO may be consistent with the clinical phenotype like eyelid edema, exophthalmos, and excess tearing. Downregulation of MAB21L1, PIK3C2G, and CLVS2 in TAO tissue demonstrates dysregulation of differentiation, oxidative stress, and developmental pathways.

糖尿病微血管并发症作为糖尿病最常见的慢性并发症,是引起患者发生残疾、死亡的主要原因,但目前其发病机制尚不明确.近期研究表明,自噬作为机体重要的内源性防御机制,广泛参与调控糖尿病视网膜病变、糖尿病肾病、糖尿病周围神经病变等糖尿病微血管病变.本文就细胞自噬与3 种糖尿病微血管并发症关系的研究进展进行综述,为临床预防和治疗提供思路.