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Experimental Eye Research Sep 2023Our previous research shown that tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) is elevated in the plasma extracellular vesicles and vitreous humor in diabetic...
Our previous research shown that tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) is elevated in the plasma extracellular vesicles and vitreous humor in diabetic retinopathy (DR). TNFAIP8 also significantly increases the viability of human retinal microvascular endothelial cells (HRMECs) and promotes cell migration and tube formation in vitro. To comprehensively explore its role in DR, we investigated the effect of TNFAIP8 on DR development using an animal model in this study. A TNFAIP8-overexpressing adeno-associated virus (AAV) vector and streptozotocin-induced mouse model was used. The AAV-TNFAIP8 vector was injected into the mice intravitreally, and the effect was evaluated. The evaluation included analysis of retinal structure and function using electroretinography, optical coherence tomography, and histological assessment. The influence of TNFAIP8 on the avascular area, retinal leukostasis, and the expression levels of inflammatory factors was also determined. TNFAIP8 significantly decreased a/b-wave amplitude and retinal thickness in diabetic mice. Histological assessment showed that TNFAIP8 aggravated pathological abnormalities with distorted organization of the retina. TNFAIP8 also significantly increased the avascular area, leukostasis, and the expression of inflammatory factors, such as TNFα, IL1β, ICAM1, and GFAP, in the retina. The results of this study support the role of TNFAIP8 in DR pathogenesis. A mechanistic understanding of TNFAIP8 may offer novel therapeutic strategies.
Topics: Mice; Humans; Animals; Diabetic Retinopathy; Tumor Necrosis Factor-alpha; Diabetes Mellitus, Experimental; Factor VIII; Endothelial Cells; Leukostasis; Retina; Apoptosis Regulatory Proteins
PubMed: 37451566
DOI: 10.1016/j.exer.2023.109572 -
BMC Medical Genomics Oct 2023This study aims to investigate the potential bidirectional causal relationship between myopia and vitreous disorders from a genetic perspective, as vitreous disorders...
PURPOSE
This study aims to investigate the potential bidirectional causal relationship between myopia and vitreous disorders from a genetic perspective, as vitreous disorders have been found to be closely associated with myopia development.
METHODS
To achieve this, a two-sample Mendelian randomization (MR) design was employed. The study utilized pooled statistics from independent genome-wide association studies. Myopia was chosen as the exposure factor, while five different vitreous disorders were considered as outcomes. The primary analytical method was the inverse variance weighting (IVW) method, supplemented by sensitivity analysis.
RESULTS
The study yielded significant findings indicating a positive association between myopia and vitreous disorders. The genetic prediction of myopia consistently demonstrated a positive correlation with vitreous disorders, as evidenced by IVW (odds ratio [OR] = 18.387; P < 0.01), MR Egger (OR = 2784.954; P < 0.01), weighted median (OR = 30.284; P < 0.01), and weighted mode (OR = 57.381; P < 0.01). All sensitivity analyses further validated these associations. Furthermore, a significant association was observed between myopia and other unspecified vitreous body disorders (IVW: OR = 57.729; P < 0.01).
CONCLUSION
Studies mainly conducted in European populations have confirmed that myopia, extending beyond early high myopia, plays a crucial role in influencing vitreous disorders and that there is a unidirectional causal relationship between myopia and vitreous disorders. Additionally, a causal relationship was identified between myopia and other unspecified vitreous disordes. These findings introduce fresh perspectives for the clinical management of unspecified vitreous disorders and contribute to the understanding of the effect of myopia on vitreous disorders. Myopia prevention and treatment will aid in slowing down the process of vitreous liquefaction and subsequently decrease the incidence of malignant eye conditions.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Myopia; Odds Ratio; Syndrome
PubMed: 37814298
DOI: 10.1186/s12920-023-01673-x -
American Journal of Ophthalmology Jun 2024To assess the consistencies of anti-Toxocara IgG (T-IgG) and Goldmann-Witmer coefficient (GWC) between paired aqueous humor (AH) and vitreous samples from patients with...
PURPOSE
To assess the consistencies of anti-Toxocara IgG (T-IgG) and Goldmann-Witmer coefficient (GWC) between paired aqueous humor (AH) and vitreous samples from patients with clinically-suspected ocular toxocariasis (OT).
DESIGN
Inter-test reliability assessment.
METHODS
A total of 47 patients with clinically-suspected OT who underwent vitrectomy were included. AH, vitreous and serum samples from each patient were collected and levels of specific T-IgG in them were detected. The association and agreement of T-IgG and GWC between AH and vitreous were evaluated. The area under the receiver operating characteristic curve (AUROC) was generated to assess the diagnostic performance of AH.
RESULTS
The T-IgG levels and GWC values in vitreous were higher than those in AH (P = 0.023 and P = 0.029, respectively), but similar positivity rates in the T-IgG (P = 1.000) and GWC>3 (P = 1.000) were apparent between vitreous and AH. In addition, there was a positive correlations between the AH and vitreous T-IgG levels (r = 0.944, P < 0.001) and the GWC values (r = 0.455, P = 0.022). Moreover, the consistencies between AH and vitreous samples in their T-IgG and GWC positivity rates were almost perfect (both, κ = 0.915, 95% CI, 0.799-1.000) in both. The AUROC reached 0.991, with a 95% confidence interval of 0.971-1.000. The best cut-off value for accurate OT diagnosis was found at 1.434, yielding 96% sensitivity and 100% specificity.
CONCLUSIONS
Our findings demonstrate that AH and vitreous samples had significant correlations and perfect agreements for both T-IgG and GWC, suggesting that the AH may serve as a proxy for vitreous to provide a safer, earlier, and more convenient screening of OT.
PubMed: 38871266
DOI: 10.1016/j.ajo.2024.05.035 -
Experimental Eye Research Oct 2023Previous studies have reported that inflammatory cytokine levels increase in the intraocular fluids (aqueous humor and vitreous) of highly myopic eyes, However, there...
Previous studies have reported that inflammatory cytokine levels increase in the intraocular fluids (aqueous humor and vitreous) of highly myopic eyes, However, there has been currently no study revealing the levels of inflammatory cytokines in tear. Therefore, this study aimed to determine tear cytokine levels of highly myopic eyes, and their relationships with myopic macular degeneration (MMD). This case-control study screened inflammatory cytokines of tear samples from 132 highly myopic and 105 emmetropic eyes using a multiplex cytokine antibody array, and cytokines showing significant intergroup differences were further validated using ProQuantum immunoassays in tear samples from another 60 highly myopic and 60 emmetropic eyes. Ultra-widefield fundus photographs of eyes were classified according to the meta-analyses of the Pathologic Myopia Classification. Associations between tear cytokine levels and MMD category were investigated. As a result, tear levels of interleukin (IL)-6, IL-13 and monocyte chemoattractant protein (MCP)-1 were screened significantly higher in highly myopic eyes than in emmetropic controls (IL-6: 11.70 ± 16.81 versus 8.22 ± 10.76 pg/mL; MCP-1: 63.60 ± 54.40 versus 33.87 ± 43.82 pg/mL; both P < 0.05). Validation assays further demonstrated the elevated concentrations of IL-6 and MCP-1 (IL-6: 13.97 ± 8.41 versus 8.06 ± 7.94 pg/mL, P < 0.001; MCP-1: 32.69 ± 8.41 versus 18.07 ± 8.41 pg/mL, P = 0.003). Tear levels of IL-6 and MCP-1 differed significantly among MMD categories (both P < 0.05). The area under receiver operating characteristic curve were 0.783 and 0.682 respectively (both P < 0.05), when using tear IL-6 and MCP-1 levels to predict the presence of MMD (category ≥2). The ordered logistic regression model also indicated that longer axial length, and higher IL-6 and MCP-1 tear levels were independent predictors of higher MMD category. In our study, highly myopic eyes presented significantly higher levels of tear IL-6 and MCP-1, which may also serve as potential biomarkers for MMD.
Topics: Humans; Cytokines; Interleukin-6; Case-Control Studies; Myopia, Degenerative; Macular Degeneration; Biomarkers; Fundus Oculi
PubMed: 37704045
DOI: 10.1016/j.exer.2023.109648 -
International Ophthalmology May 2024To evaluate the levels of anxiety and depression in patients with symptomatic vitreous floaters and to determine the possible correlations of psychological implications...
PURPOSE
To evaluate the levels of anxiety and depression in patients with symptomatic vitreous floaters and to determine the possible correlations of psychological implications with the symptoms duration and possible improvement, the degree of posterior vitreous detachment, and the discomfort severity.
METHODS
Ninety patients complaining for floaters and fifty-seven age- and gender-matched healthy-control subjects were recruited. Every participant underwent a complete ophthalmological examination, including funduscopy and optical coherence tomography scans, while clinical and demographic data were also gathered. The Patient Health Questionnaire-9 (PHQ-9), the Zung Depression Inventory-Self-Rating Depression Scale (Zung SDS), and the Hospital Anxiety and Depression Scale (HADS) were completed by everyone.
RESULTS
Between the studied groups, no significant differences were detected regarding the clinical and demographic data (p > 0.05). The patients with floaters had significantly higher scores of PHQ-9, Zung SDS, HADS Anxiety, and HADS Depression (p < 0.001). After adjustment for several confounders, PHQ-9 (p = 0.041), Zung SDS (p = 0.003), and HADS Anxiety (p = 0.036) values remained significantly impaired. Among the patients, PHQ-9 and Zung SDS scores were significantly elevated in the patients with floaters duration less than 4 weeks (p < 0.05). Finally, anxiety and depression were significantly correlated with the symptoms duration and intensity, with the floater-associated discomfort, and with the stage of posterior vitreous detachment.
CONCLUSION
Vitreous floaters have a negative impact on patients' psychological status, by the terms of enhanced depressive and anxiety levels. To the best of our knowledge, our study is the first in the literature to elaborate the aforementioned association, by assessing three different questionnaires simultaneously.
Topics: Humans; Male; Female; Middle Aged; Vitreous Body; Depression; Adult; Anxiety; Eye Diseases; Tomography, Optical Coherence; Surveys and Questionnaires; Aged; Case-Control Studies; Vitreous Detachment; Vision Disorders
PubMed: 38713290
DOI: 10.1007/s10792-024-03006-y -
Molecular Vision 2023Increased inflammatory factor levels have been reported in the vitreous humor (VH) of diabetic retinopathy and neovascular age-related macular degeneration, ocular...
PURPOSE
Increased inflammatory factor levels have been reported in the vitreous humor (VH) of diabetic retinopathy and neovascular age-related macular degeneration, ocular diseases generally associated with the formation of new retinal blood vessels and leakage. However, the levels of inflammatory mediators are less known in retinal degeneration without neovascularization. Human retinitis pigmentosa (RP) and animal models of light-induced retinal degeneration (LIRD) share several features, such as photoreceptor death and retinal inflammation. Here, we aimed to determine the levels of inflammatory factors in the VH of the LIRD mouse model.
METHODS
LIRD was induced by exposing BALB/c mice to white light (15,000 lx, 2 h), and the mice were recovered for 2 days before analysis (n = 50 mice). We assessed retinal morphology using optical coherence tomography and hematoxylin and eosin staining; retinal cell viability was determined using terminal deoxynucleotidyl transferase dUTP nick-end labeling, and retinal responses were measured based on electroretinogram signals. Total retinal RNAs were extracted and subjected to RNA sequencing analysis. VH samples from control (n = 4) and LIRD mice (n = 9) were assayed in triplicate for a panel of four inflammatory mediators using the Simple Plex Cartridge on an Ella System.
RESULTS
Retinal degeneration, photoreceptor death, infiltration of microglia/macrophages into the photoreceptor layer, and loss of a- and b-waves were obviously detected after LIRD. RNA sequencing revealed that light damage (LD) led to the significant upregulation of inflammatory factors in mouse retinas. In the VH, LD increased the total protein concentration. Dramatic induction of CCL2 (~3000 fold) and IL6 (~10 fold) was detected in VH in response to LD. Increased but not significant levels of TNFα and IL1β were also detected in light-exposed VH.
CONCLUSIONS
Given that the LIRD model mimics RP pathogenesis in some aspects, these results suggest a causative link between retinal degeneration and VH inflammation in RP progression, and the increased CCL2 level in VH may reflect similar elevated CCL2 expression in the degenerative retina.
Topics: Mice; Humans; Animals; Retinal Degeneration; Vitreous Body; Retina; Retinitis Pigmentosa; Inflammation; Disease Models, Animal; Inflammation Mediators
PubMed: 38222454
DOI: No ID Found -
Journal of Neuroinflammation Dec 2023Neuroinflammation and mitochondrial dysfunction play crucial roles in retinal ischemia and reperfusion (IR) injury. Recent studies have identified mitochondrial function...
BACKGROUND
Neuroinflammation and mitochondrial dysfunction play crucial roles in retinal ischemia and reperfusion (IR) injury. Recent studies have identified mitochondrial function as a promising target for immunomodulation. Empagliflozin (EMPA), an anti-diabetic drug, has exhibited great potential as both an anti-inflammatory agent and a protector of mitochondrial health. This study aimed to assess the therapeutic efficacy of EMPA in retinal IR injury.
METHODS
To evaluate the protective effects of EMPA, the drug was injected into the vitreous body of mice post-retinal IR. Single-cell RNA sequencing (scRNA-seq) analysis was conducted to uncover the underlying mechanisms, and the results were further validated through in vivo and in vitro experiments.
RESULTS
EMPA effectively protected retinal ganglion cells (RGCs) from IR injury by attenuating local retinal inflammation. The scRNA-seq analysis revealed that EMPA downregulated the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) signaling pathway and restored mitochondrial dynamics by upregulating the expression of mitochondrial fusion-related genes, Mitofusin 1 (Mfn1) and optic atrophy 1 (Opa1). These findings were further corroborated by Western blotting. In vitro experiments provided additional insights, demonstrating that EMPA suppressed lipopolysaccharide (LPS)-induced cell inflammation and NLRP3 inflammasome activation. Moreover, EMPA enhanced mitochondrial fusion, neutralized mitochondrial reactive oxygen species (mtROS), and restored mitochondrial membrane potential (MMP) in BV2 microglia. Notably, genetic ablation of Mfn1 or Opa1 abolished the anti-inflammatory effects of EMPA.
CONCLUSIONS
Our findings highlight the positive contribution of Mfn1 and Opa1 to the anti-inflammatory therapeutic effect of EMPA. By restoring mitochondrial dynamics, EMPA effectively mitigates microglia-mediated neuroinflammation and prevents RGC loss in retinal IR injury.
Topics: Mice; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Neuroinflammatory Diseases; Microglia; Reperfusion Injury; Ischemia; Anti-Inflammatory Agents; GTP Phosphohydrolases
PubMed: 38082266
DOI: 10.1186/s12974-023-02982-9 -
Journal of Controlled Release :... Jan 2024Nanoscale extracellular vesicles (EVs), consisting of exomers, exosomes and microvesicles/ectosomes, have been extensively investigated in the last 20 years, although... (Review)
Review
Nanoscale extracellular vesicles (EVs), consisting of exomers, exosomes and microvesicles/ectosomes, have been extensively investigated in the last 20 years, although their biological role is still something of a mystery. EVs are involved in the transfer of lipids, nucleic acids and proteins from donor to recipient cells or distant organs as well as regulating cell-cell communication and signaling. Thus, EVs are important in intercellular communication and this is not limited to sister cells, but may also mediate the crosstalk between different cell types even over long distances. EVs play crucial functions in both cellular homeostasis and the pathogenesis of diseases, and since their contents reflect the status of the donor cell, they represent an additional valuable source of information for characterizing complex biological processes. Recent advances in isolation and analytical methods have led to substantial improvements in both characterizing and engineering EVs, leading to their use either as novel biomarkers for disease diagnosis/prognosis or even as novel therapies. Due to their capacity to carry biomolecules, various EV-based therapeutic applications have been devised for several pathological conditions, including eye diseases. In the eye, EVs have been detected in the retina, aqueous humor, vitreous body and also in tears. Experiences with other forms of intraocular drug applications have opened new ways to use EVs in the treatment of retinal diseases. We here provide a comprehensive summary of the main in vitro, in vivo, and ex vivo literature-based studies on EVs' role in ocular physiological and pathological conditions. We have focused on age-related macular degeneration, diabetic retinopathy, glaucoma, which are common eye diseases leading to permanent blindness, if not treated properly. In addition, the putative use of EVs in retinitis pigmentosa and other retinopathies is discussed. Finally, we have reviewed the potential of EVs as therapeutic tools and/or biomarkers in the above-mentioned retinal disorders. Evidence emerging from experimental disease models and human material strongly suggests future diagnostic and/or therapeutic exploitation of these biological agents in various ocular disorders with a good possibility to improve the patient's quality of life.
Topics: Humans; Quality of Life; Extracellular Vesicles; Biomarkers; Retina; Retinal Diseases; Eye Diseases
PubMed: 38013069
DOI: 10.1016/j.jconrel.2023.11.035 -
Graefe's Archive For Clinical and... Aug 2023Foldable capsular vitreous body (FCVB) is an emerging vitreous substitute that has been recently introduced to treat various advanced vitreoretinal conditions including... (Review)
Review
PURPOSE
Foldable capsular vitreous body (FCVB) is an emerging vitreous substitute that has been recently introduced to treat various advanced vitreoretinal conditions including severe ocular trauma, complicated retinal detachment (RD), and proliferative vitreoretinopathy.
METHODS
Review protocol was prospectively registered at PROSPERO (CRD42022342310). A systematic literature search using PubMed, Ovid MEDLINE, and Google Scholar for articles published until May 2022 was performed. The search included the following keywords: foldable capsular vitreous body, FCVB, artificial vitreous substitutes, and artificial vitreous implants. Outcomes included indications of FCVB, anatomical success rates, postoperative intraocular pressure (IOP), best-corrected visual acuity (BCVA), and complications.
RESULTS
A total of 17 studies that utilized FCVB up to May 2022 were included. FCVB was used intraocularly as a tamponade or extraocularly as a macular/scleral buckle for various retinal conditions including severe ocular trauma, simple and complex RD, silicone oil-dependent eyes, and highly myopic eyes with foveoschisis. FCVB was reported to be successfully implanted in the vitreous cavity of all patients. Final retinal reattachment rate ranged from 30 to 100%. Postoperative IOP improved or was maintained in most eyes, with low postoperative complication rates. Improvement in BCVA ranged from 0 to 100% of subjects.
CONCLUSION
Indications of FCVB implantation have recently widened to include multiple advanced ocular conditions such as complex RD, but also include simpler conditions as uncomplicated RD. FCVB implantation showed good visual and anatomical outcomes, few IOP fluctuations, and a good safety profile. Larger comparative studies are required to further evaluate FCVB implantation.
Topics: Vitreous Body; Retinal Detachment; Vitrectomy; Eye Injuries; Vitreoretinopathy, Proliferative; Humans; Orbital Implants; Intraocular Pressure
PubMed: 36795160
DOI: 10.1007/s00417-023-05995-5 -
Ocular Immunology and Inflammation Sep 2023Endogenous endophthalmitis (EE) is an uncommon but potentially devastating ocular infection involving the inner layers of the eye. The global incidence of EE is on the...
Endogenous endophthalmitis (EE) is an uncommon but potentially devastating ocular infection involving the inner layers of the eye. The global incidence of EE is on the rise. Common ocular signs and symptoms associated with EE include conjunctival injection, ocular pain, and reduced visual acuity. On clinical examination, a history of prior or coexisting systemic infections, symptoms (e.g., fever, malaise), and localizing features may be noted. Clinical diagnosis is often challenging, resulting in critical delays that contribute to a poor prognosis. Blood cultures and ocular fluid samples can aid in conforming causative pathogen(s), after which empirical antibiotic therapy, both systemic and intravitreal, should be instated. The use of steroids to suppress inflammation remains controversial. Surgical options include pars plana vitrectomy. Overall prognosis varies depending on host and pathogen factors, and early diagnosis and initiation of appropriate treatment are crucial.
Topics: Humans; Vitreous Body; Retrospective Studies; Endophthalmitis; Vitrectomy; Eye Infections, Fungal; Anti-Bacterial Agents
PubMed: 36306406
DOI: 10.1080/09273948.2022.2126863