ABSTRACT
The precise role and innate immunological mechanisms underlying lymphangiogenesis in pterygium remain unclear. This study aimed to investigate the presence of M1 and M2 macrophages and their correlation with pro-lymphangiogenic activation and lymphatic endothelial expression in human pterygium stromal tissues. We analyzed human pterygium and subject-matched normal conjunctival tissues for the expression of these factors and conducted in vitro experiments to assess interactions between macrophages and pterygium fibroblasts. Myeloid and M1 macrophage markers were upregulated in pterygium. M1 macrophages were associated with the upregulation of pro-lymphangiogenic vascular endothelial growth factor C (Vegfc) in pterygium tissues and induced inflammatory signals in pterygium fibroblasts. In contrast, lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1) expression was associated with M2 markers but not with M1 markers. Notably, the clinical severity of pterygium was inversely correlated with the expression of the M2 marker Cd163. These findings suggest that M1 and M2 macrophages play distinct roles in the pathogenesis of pterygium, with M1 macrophages enhancing lymphangiogenic stimulation and inflammatory responses, while M2 macrophages are associated with Lyve1 expression and reduced severity of pterygium. Understanding these mechanisms may advance our current understanding of lymphatic biology in pterygium.
Subject(s)
Conjunctiva , Lymphangiogenesis , Macrophages , Pterygium , Humans , Pterygium/metabolism , Pterygium/pathology , Macrophages/metabolism , Male , Female , Middle Aged , Conjunctiva/metabolism , Conjunctiva/pathology , Fibroblasts/metabolism , Fibroblasts/pathology , Vascular Endothelial Growth Factor C/metabolism , Vesicular Transport Proteins/metabolism , Macrophage Activation , Lymphatic Vessels/pathology , Lymphatic Vessels/metabolism , Cells, Cultured , Aged , Antigens, CD/metabolism , Biomarkers/metabolism , AdultABSTRACT
BACKGROUND: Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent ß-blocker. METHODS: Of these, 176 patients used a ß-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent ß-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan-Meier survival analysis. RESULTS: Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent ß-blocker-usage groups, respectively. Kaplan-Meier survival analysis indicated that half of the allergies in the concurrent ß-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent ß-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent ß-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent ß-blocker-usage group. CONCLUSIONS: Concurrent use of ß-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of ß-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.
Subject(s)
Adrenergic beta-Antagonists , Brimonidine Tartrate , Drug Combinations , Glaucoma , Ophthalmic Solutions , Sulfonamides , Thiazines , Humans , Male , Female , Retrospective Studies , Brimonidine Tartrate/administration & dosage , Brimonidine Tartrate/therapeutic use , Brimonidine Tartrate/adverse effects , Aged , Adrenergic beta-Antagonists/therapeutic use , Adrenergic beta-Antagonists/administration & dosage , Thiazines/administration & dosage , Thiazines/therapeutic use , Thiazines/adverse effects , Middle Aged , Prevalence , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Glaucoma/epidemiology , Glaucoma/drug therapy , Drug Hypersensitivity/epidemiology , Carbonic Anhydrase Inhibitors/administration & dosage , Carbonic Anhydrase Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/administration & dosage , Drug Therapy, Combination , Intraocular Pressure/physiology , Intraocular Pressure/drug effects , Aged, 80 and overABSTRACT
Glaucoma is a vision-threatening disorder characterized by progressive death of retinal ganglion cells (RGCs), although little is known about therapeutic milestones. Due to its complex and multifactorial pathogenesis, multipronged therapeutic approach is needed. Angiogenin (ANG), now called ribonuclease (RNase) 5, has been previously known as angiogenic factor and more recently its biologic activity is extended to promoting cell survival via its ribonucleolytic activity. Here, we revealed the defect of ANG in human glaucomatous trabecular meshwork (TM) cells and identified novel multiple functions of ANG as an anti-glaucomatous strategy. ANG was highly expressed in normal eyes and normal TM cells compared to glaucomatous TM cells. ANG induced intraocular pressure (IOP) lowering in rat models of both normal and elevated IOP, and as a possible mechanism, activated Akt-mediated signals for nitric oxide (NO) production, an important regulator of IOP in glaucomatous TM cell. Moreover, we demonstrated ANG-induced production of matrix metalloproteinase (MMP)-1 and -3 and rho-kinase inhibition for TM remodeling. For anti-glaucomatous defense optimization, ANG not only elicited immune-modulative pathways via indolamine 2,3-dioxygenase (IDO) activation in TM cells and suppression of Jurkat T cells, but also rescued neural stem cells (NSCs) from apoptosis induced by glaucomatous stress. These results demonstrate that novel multi-functional effects of ANG may have benefits against glaucoma in ocular tissues.
Subject(s)
Apoptosis , Glaucoma/physiopathology , Intraocular Pressure , Neural Stem Cells/pathology , Ribonuclease, Pancreatic/metabolism , Trabecular Meshwork/physiopathology , Animals , Cell Line , Cells, Cultured , Glaucoma/metabolism , Glaucoma/pathology , Humans , Jurkat Cells , Male , Neural Stem Cells/metabolism , Rats, Sprague-Dawley , Ribonuclease, Pancreatic/analysis , Trabecular Meshwork/cytology , Trabecular Meshwork/metabolism , Trabecular Meshwork/pathologyABSTRACT
The clinical manifestations of pterygium are characterized by rapid growth and postoperative recurrences. We had previously proposed that hypoxia-inducible factor (HIF)-1α recruits progenitor cells during the development and progression of pterygia. Recently, it was reported that various stimuli, including inflammation, could activate HIF-1α even under normoxic conditions. The ocular surface directly faces external environments, and is thus frequently exposed to inflammatory insults. First, we examined the gene expression of HIF-1α, its downstream molecule, vascular endothelial growth factor (VEGF)-A, and VEGF receptor (VEGFR)-2 in corneal and conjunctival cells compared with cultured human umbilical vein endothelial cells. Corneal fibroblasts had high expression of VEGFR-2 in the presence of TNF-α, and HIF-1α was activated by TNF-α in diverse ocular surface cells. The HIF-1α/VEGF/VEGFR signaling pathway in response to TNF-α was evaluated in cultured human pterygium fibroblasts (HPFs) at the gene and protein levels and was compared to treatment with cobalt chloride (CoCl2), a hypoxic mimetic, to exclude the effect of hypoxia. Although VEGF-A expression was not changed by TNF-α, expression of HIF-1α and VEGFR-2 was enhanced in HPFs treated with TNF-α, independent of hypoxia conditioning. In addition, VEGF-C gene expression was activated solely by TNF-α in HPF, but VEGF-B levels were not significantly affected. These results may provide mechanistic explanations for the uniquely vigorous proliferation of pterygium fibrovascular tissue during TNF-α-induced ocular surface inflammation.
Subject(s)
Fibroblasts/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Pterygium/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Cell Hypoxia/physiology , Cells, Cultured , Cornea/cytology , Fibroblasts/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Hypoxia/metabolism , RNA, Messenger/metabolism , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation/drug effects , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor B/metabolism , Vascular Endothelial Growth Factor C/metabolismABSTRACT
Activation of fibroblasts is a vital process during wound healing. However, if prolonged and exaggerated, profibrotic pathways lead to tissue fibrosis or scarring and further organ malfunction. Although the pathogenesis of pterygium is known to be multi-factorial, additional studies are needed to better understand the pathways initiated by fibroblast activation for the purpose of therapeutic translation. Regarding pterygium as a possible systemic disorder, we discuss the different cell types that pterygium fibroblasts originate from. These may include bone marrow-derived progenitor cells, cells undergoing epithelial-mesenchymal transition (EMT), and local resident stromal cells. We also describe how pterygium fibroblasts can be activated and perpetuate profibrotic signaling elicited by various proliferative drivers, immune-inflammation, and novel factors such as stromal cell-derived factor-1 (SDF-1) as well as a known key fibrotic factor, transforming growth factor-beta (TGF-ß). Finally, epigenetic modification is discussed to explain inherited susceptibility to pterygium.
Subject(s)
Fibroblasts/pathology , Myofibroblasts/pathology , Pterygium/pathology , Cytokines/metabolism , Epigenesis, Genetic , Epithelial-Mesenchymal Transition , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Myofibroblasts/immunology , Pterygium/genetics , Pterygium/immunology , Pterygium/metabolismABSTRACT
BACKGROUND: Postoperative adhesion is one of the major complications of strabismus surgery and result in motility dysfunction that brings unpredictable surgical outcomes. However, there was no definitely accepted treatment method to prevent postoperative adhesion. METHODS: A prospective, randomized, controlled experimental animal study was performed. Both eyes of each of 14 New Zealand White rabbits underwent superior rectus muscle recession. After the surgical procedure, the subjects were divided randomly into two groups; 0.5 % tranilast ophthalmic solutions and fluoroquinolone antibiotic eye drops were administered to the group tranilast (N = 14), while the group control (N = 14) received fluoroquinolone eye drops only. Five weeks after surgery, we evaluated gross adhesions with a numeric score (0 to 4). In addition, histopathologic examination with hematoxylin & eosin staining, Masson's-trichrome staining, and anti-transforming growth factor beta 1 (TGF-ß1) immuno-histochemical staining were done. RESULTS: The group tranilast showed significantly less gross adhesion and inflammation than the group control (P = 0.01 and P < 0.001, respectively). Masson's-trichrome staining revealed that post-operative collagen deposition was more prominent in the group control than the group tranilast (P < 0.001). Moreover, remarkable TGF-ß1 expression was observed in areas with excessive collagen deposition. CONCLUSIONS: Instillation of 0.5 % tranilast ophthalmic solution is a simple and effective method for preventing post-operative adhesion after strabismus surgery.
ABSTRACT
BACKGROUND: In 2014, the overall rate of smartphone use in Korea was 83 and 89.8 % in children and adolescents. The rate of smartphone use differs according to region (urban vs. rural) and age (younger grade vs. older grade). We investigated risk and protective factors associated with pediatric dry eye disease (DED) in relation to smartphone use rate according to region and age. METHODS: We enrolled 916 children and performed an ocular exam that included slit lamp exam and tear break-up time. A questionnaire administered to children and their families consisted of video display terminal (VDT) use, outdoor activity, learning, and modified ocular surface disease index (OSDI) score. DED was defined based on the International Dry Eye Workshop guidelines (Objective signs: punctate epithelial erosion or short tear break-up time; subjective symptoms: modified OSDI score) We performed statistical analysis of risk factors and protective factors in children divided into groups as follows: DED vs. control, urban vs. rural, younger grade (1st to 3rd) vs. older grade (4th to 6th). RESULTS: A total of 6.6 % of children were included in the DED group, and 8.3 % of children in the urban group were diagnosed with DED compared to 2.8 % in the rural group (P = 0.03). The rate of smartphone use was 61.3 % in the urban group and 51.0 % in the rural group (P = 0.04). In total, 9.1 % of children in the older-grade group were diagnosed with DED compared to 4 % in the younger-grade group (P = 0.03). The rate of smartphone use was 65.1 % in older-grade children and 50.9 % in younger-grade children (P < 0.001). The mean daily duration of smartphone use was longer in the DED group than controls (logistic regression analysis, P < 0.001, OR = 13.07), and the mean daily duration of outdoor activities was shorter in the DED group than controls (logistic regression analysis, P < 0.01, OR = 0.33). After cessation of smartphone use for 4 weeks in the DED group, both subjective symptoms and objective signs had improved. CONCLUSIONS: Smartphone use in children was strongly associated with pediatric DED; however, outdoor activity appeared to be protective against pediatric DED. Older-grade students in urban environments had DED risk factors (long duration of smartphone use), and a short duration of outdoor activity time. Therefore, close observation and caution are needed when older children in urban areas use smartphones.
Subject(s)
Dry Eye Syndromes/etiology , Smartphone , Age Factors , Case-Control Studies , Child , Cross-Sectional Studies , Dry Eye Syndromes/epidemiology , Dry Eye Syndromes/prevention & control , Female , Humans , Logistic Models , Male , Prevalence , Recreation , Republic of Korea/epidemiology , Risk Factors , Rural Population/statistics & numerical data , Sex Factors , Urban Population/statistics & numerical data , Visual AcuityABSTRACT
BACKGROUND: Angiogenin (ANG), a component of tears, is involved in the innate immune system and is related with inflammatory disease. We investigated whether ANG has an immune modulatory function in human corneal fibroblasts (HCFs). METHODS: HCFs were cultured from excised corneal tissues. The gene or protein expression levels of interleukin (IL)-1beta (ß), IL-4, IL-6, IL-8, IL-10, complements, toll-like receptor (TLR)4, myeloid differentiation primary response gene (MYD)88, TANK-binding kinase (TBK)1, IkappaB kinase-epsilon (IKK-ε) and nuclear factor-kappaB (NF-κB) were analyzed with or without ANG treatment in tumor necrosis factor-alpha (TNF-α)- or lipopolysaccharide (LPS)-induced inflammatory HCFs by real-time polymerase chain reaction (PCR), Western blotting and immunocytochemistry. Inflammatory cytokine profiles with or without ANG were evaluated through immunodot blot analysis in inflammatory HCFs. Corneal neovascularization and opacity in a rat model of corneal alkali burn were evaluated after application of ANG eye drops. RESULTS: ANG decreased the mRNA levels of IL-1ß, IL-6, IL-8, TNF-α receptor (TNFR)1, 2, TLR4, MYD88, and complement components except for C1r and C1s and elevated the mRNA expression of IL-4 and IL-10. Increased signal intensity of IL-6, IL-8 and monocyte chemotactic protein (MCP)-1 and MCP-2 induced by TNF-α or LPS was weakened by ANG treatment. ANG reduced the protein levels of IKK-ε by either TNF-α and LPS, and decreased TBK1 production induced by TNF-α, but not induced by LPS. The expression of NF-κB in the nuclei was decreased after ANG treatment. ANG application lowered corneal neovascularization and opacity in rats compared to controls. CONCLUSION: These results demonstrate that ANG reduces the inflammatory response induced by TNF-α or LPS in HCFs through common suppression of IKK-ε-mediated activation of NF-κB. This may support the targeting of immune-mediated corneal inflammation by using ANG.
Subject(s)
Angiogenesis Inducing Agents/pharmacology , Cornea/drug effects , Corneal Neovascularization/drug therapy , Corneal Neovascularization/immunology , Corneal Opacity/drug therapy , Corneal Opacity/immunology , Fibroblasts/drug effects , Immunity, Innate/drug effects , Ribonuclease, Pancreatic/pharmacology , Animals , Blotting, Western , Burns, Chemical/drug therapy , Burns, Chemical/immunology , Chemokines/metabolism , Cornea/metabolism , Cornea/pathology , Cytokines/metabolism , Disease Models, Animal , Eye Burns/drug therapy , Eye Burns/immunology , Fibroblasts/metabolism , Humans , Immunohistochemistry , Interleukins/metabolism , Male , Polymerase Chain Reaction/methods , RNA, Messenger/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
The aim of this study was to provide an understanding of how residents in apartment buildings perceive and react to impact sounds coming from the upstairs neighbours' dwellings. Based on existing theoretical and empirical studies on environmental noise, a conceptual model was developed to explain relationships among noise annoyance and non-acoustic factors. The model was then tested using structural equation modelling with survey data from residents living in apartment buildings (N = 487). The findings showed that the conceptual model was consistent with other models developed for environmental noises. The results indicated that annoyance induced by floor impact noise was associated with perceived disturbance, coping, and self-reported health complaints. Noise sensitivity had a direct impact on perceived disturbance and an indirect impact on annoyance, and moderating variables affected the non-acoustic factors. Exposure to footstep noises increased the impact size of noise sensitivity to disturbance. Predictability, marital status, and house ownership were found to influence the relationship between attitudes towards authorities and coping. In addition, a negative attitude towards neighbours (i.e., the noise source) moderated the positive relationship between annoyance and coping.
ABSTRACT
Angiogenin (ANG) is reportedly multifunctional, with roles in angiogenesis and autoimmune diseases. This protein is involved in the innate immune system and has been implicated in several inflammatory diseases. Although ANG may be involved in the anti-inflammatory response, there is no evidence that it has direct anti-inflammatory effects. In this study we sought to determine whether ANG has an anti-inflammatory effect in human corneal fibroblasts (HCFs) exposed to media containing tumor necrosis factor-alpha (TNF-α). We found that ANG reduced the mRNA expression of interleukin-1 beta (IL-1ß), -6, -8 and TNF-α receptors (TNFR) 1 and 2. In contrast, ANG increased the mRNA expression of IL-4 and -10. Protein levels of TANK-binding kinase 1 (TBK1) were reduced by ANG in HCFs treated with TNF-α. Moreover, ANG diminished the expression of IL-6 and -8 and monocyte chemotactic protein- (MCP-) 1. The protein expression of nuclear factor-κB (NF-κB) was downregulated by ANG treatment. These findings suggest that ANG suppressed the TNF-α-induced inflammatory response in HCFs through inhibition of TBK1-mediated NF-κB nuclear translocation. These novel results are likely to play a significant role in the selection of immune-mediated inflammatory therapeutic targets and may shed light on the pathogenesis of immune-mediated inflammatory diseases.
Subject(s)
Cornea/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Protein Serine-Threonine Kinases/metabolism , Ribonuclease, Pancreatic/pharmacology , Cells, Cultured , Chemokine CCL2/metabolism , Humans , Interleukin-6/metabolism , Interleukin-8/metabolism , NF-kappa B/metabolism , Protein Serine-Threonine Kinases/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The purpose of this study was to elucidate the origin and cellular composition of retrocorneal membranes (RCMs) associated with chemical burns using immunohistochemical staining for primitive cell markers. Six cases of RCMs were collected during penetrating keratoplasty. We examined RCMs with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS) staining and immunohistochemical analysis using monoclonal antibodies against hematopoietic stem cells (CD34, CD133, c-kit), mesenchymal stem cells (beta-1-integrin, TGF-ß, vimentin, hSTRO-1), fibroblasts (FGF-ß, α-smooth muscle actin), and corneal endothelial cells (type IV collagen, CD133, VEGF, VEGFR1). Histologic analysis of RCMs revealed an organized assembly of spindle-shaped cells, pigment-laden cells, and thin collagenous matrix structures. RCMs were positive for markers of mesenchymal stem cells including beta-1-integrin, TGF-ß, vimentin, and hSTRO-1. Fibroblast markers were also positive, including FGF-ß and α-smooth muscle actin (SMA). In contrast, immunohistochemical staining was negative for hematopoietic stem cell markers including CD34, CD133 and c-kit as well as corneal endothelial cell markers such as type IV collagen, CD133 except VEGF and VEGFR1. Pigment-laden cells did not stain with any antibodies. The results of this study suggest that RCMs consist of a thin collagen matrix and fibroblast-like cells and may be a possible neogenetic structure produced from a lineage of bone marrow-derived mesenchymal stem cells.
Subject(s)
Cornea/cytology , Stem Cells/metabolism , Adult , Aged , Antigens, CD/metabolism , Cornea/pathology , Cytokines/metabolism , Endothelial Cells/cytology , Endothelial Cells/metabolism , Female , Fibroblasts/cytology , Fibroblasts/metabolism , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Humans , Immunohistochemistry , Intercellular Signaling Peptides and Proteins/metabolism , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Middle Aged , Stem Cells/cytologyABSTRACT
PURPOSE: To propose the optimal value of baseline corneal astigmatism and pterygial morphological profiles for primary pterygium surgery to restore the corneal optical properties. METHODS: We analysed 93 eyes from 84 subjects with nasal-only primary pterygium who underwent pterygium excision with conjunctival-limbal autograft and were assessed perioperatively using anterior segment swept-source optical coherence tomography (AS SS-OCT). We collected data on anterior corneal astigmatism (ACA) and root mean square (RMS) values for anterior corneal lower- (LoA) and higher-order aberrations (HoA) as corneal optical properties using AS SS-OCT. Using preoperative ACA and four pterygial morphological profiles (horizontal invasion length [HIL], height, thickness and the ratio of residual corneal thickness [RCT] to central corneal thickness [CCT]) measured in AS SS-OCT, we plotted receiver operating characteristic (ROC) curves. These curves aimed to determine cut-off values predicting a perioperative decrease exceeding 50% in ACA, RMS LoA and RMS HoA, as well as postoperative residual ACA higher than 1.25D. RESULTS: Preoperative ACA > 1.42D (AUC = 0.934) and >3.60D (AUC = 0.946) proved most effective in identifying subjects with perioperative decrease exceeding in ACA and RMS LoA, respectively. HIL > 3.34 mm (AUC = 0.941) was most effective in distinguishing subjects with perioperative reduction exceeding 50% in RMS HoA. Preoperative ACA > 5.78D (AUC = 0.776) and HIL > 5.03 mm (AUC = 0.700) significantly distinguished subjects with postoperative residual ACA higher than 1.25D. CONCLUSION: Optimizing the restoration of corneal astigmatism and aberrations after pterygium surgery may be facilitated by determining the optimal surgical timing based on preoperative ACA and HIL values.
Subject(s)
Conjunctiva , Limbus Corneae , Pterygium , Tomography, Optical Coherence , Humans , Pterygium/surgery , Pterygium/diagnosis , Male , Female , Conjunctiva/transplantation , Middle Aged , Tomography, Optical Coherence/methods , Aged , Limbus Corneae/surgery , Retrospective Studies , Cornea/surgery , Autografts , Visual Acuity , Ophthalmologic Surgical Procedures/methods , Astigmatism/surgery , Astigmatism/physiopathology , Astigmatism/diagnosis , Adult , Transplantation, Autologous , Follow-Up Studies , Refraction, Ocular/physiology , ROC CurveABSTRACT
This study aimed to investigate the changes in clinical parameters of dry eye disease and meibomian gland dysfunction in both the operated and untreated fellow eyes of patients who underwent unilateral cataract surgery with the short-term administration of anti-inflammatory eye drops in the surgical eye. The medical charts of 57 consecutive patients who underwent unilateral cataract surgery and received 1% prednisolone acetate and non-steroidal anti-inflammatory drug (NSAID, 0.1% bromfenac sodium) eye drops were reviewed. The preoperative ocular surface disease index questionnaire score (38.9 ± 20.5) decreased significantly to 15.2 ± 16.4 at post-surgical 1 week and further to 12.8 ± 11.4 after 1 month. Although meibum quality grade increased and corneal sensitivity decreased at 1 week in operated eyes, corneal erosion scores and Sjogren's International Collaborative Clinical Alliance ocular staining scores even improved over a month in the untreated fellow eyes. The tear matrix metalloproteinase (MMP)-9 grade decreased in both operated eyes and untreated fellow eyes after 1 month from surgery. In conclusion, the short-term topical anti-inflammatory treatment using steroid and NSAID eye drops in the operated eye after cataract surgery decreased subjective ocular surface discomfort and improved ocular surface staining scores and tear MMP-9 expression in the untreated fellow eyes.
Subject(s)
Cataract Extraction , Cataract , Dry Eye Syndromes , Humans , Ophthalmic Solutions/therapeutic use , Meibomian Glands/metabolism , Cataract Extraction/adverse effects , Tears/metabolism , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/etiology , Dry Eye Syndromes/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Cataract/metabolismABSTRACT
The protein epidermal growth factor (EGF), which plays a crucial role in promoting cell proliferation and survival, has recently demonstrated potential in reducing inflammation. In this study, we examined the impact of EGF on the anti-inflammatory and anti-proliferative properties of pterygium, a prevalent hypervascular proliferative disease affecting the ocular surface. In surgically excised tissues, markers for fibrotic and inflammatory signals, including VIM, ACTA2, FAP, MMP2, VCAM1, ICAM1, CD86, IL6, and IL1B were upregulated in the pterygium body stroma compared to the normal conjunctival stroma. EGF exerted anti-inflammatory and anti-vasculogenic effects on pterygial fibroblasts when co-cultured with M1 macrophages. Moreover, exosomes derived from EGF-preconditioned M1 macrophages suppressed the heightened inflammatory and vasculogenic signals in pterygial fibroblasts induced by exosomes from M1 macrophages. Paradoxically, the proliferation of pterygial fibroblasts was inhibited by EGF in the in vitro microenvironment with M1 macrophages, despite EGF being known as a growth factor. EGF-preconditioning of M1 macrophages rescued the increased proliferation of pterygial fibroblasts induced by exosomes from M1 macrophages. In conclusion, our findings demonstrate that EGF effectively mitigates inflammation and proliferation in pterygial fibroblasts within a microenvironment containing M1 macrophages.
Subject(s)
Cell Proliferation , Epidermal Growth Factor , Fibroblasts , Inflammation , Macrophages , Pterygium , Fibroblasts/metabolism , Fibroblasts/drug effects , Humans , Epidermal Growth Factor/pharmacology , Epidermal Growth Factor/metabolism , Macrophages/metabolism , Macrophages/drug effects , Cell Proliferation/drug effects , Pterygium/metabolism , Pterygium/pathology , Inflammation/metabolism , Inflammation/pathology , Inflammation/drug therapy , Exosomes/metabolism , Cells, Cultured , Male , Coculture Techniques , Cellular Microenvironment/drug effects , Female , Middle Aged , Conjunctiva/metabolism , Conjunctiva/pathology , Conjunctiva/drug effectsABSTRACT
Epidermal Growth Factor (EGF), a protein pivotal in cell proliferation and survival, has recently shown promise in alleviating inflammation. This study investigates EGF's impact on M1 macrophages, exploring its potential for anti-inflammatory and anti-vasculogenic interactions with corneal endothelial cells (CECs). Polarized M1 macrophages treated with EGF exhibited a suppression of gene expressions related to inflammatory and vasculogenic signals. The anti-inflammatory effects of EGF were observed in co-culture systems with human CECs (HCECs), showcasing its ability to alter macrophage phenotypes. Exosomes derived from EGF-treated M1 macrophages demonstrated enriched proteomic profiles related to immune system regulation and inflammation inhibition. When applied as eye drops in murine corneas, EGF-conditioned M1 macrophage-derived exosomes effectively reduced inflammation and increased M2-related ARG1 expression. This study highlights EGF's potential in mitigating inflammation in M1 macrophages and its delivery through exosomes to cultured HCECs and murine corneas, suggesting a novel therapeutic avenue for ocular surface anti-inflammatory treatments.
ABSTRACT
In this study, we compared the dichotomous and 5-scale grading systems for point-of-care immunoassay of tear matrix metalloproteinase (MMP)-9 in dry eye disease (DED) patients and identified the optimal dichotomous system to correlate with DED parameters. We included 167 DED patients without primary Sjogren's syndrome (pSS) (Non-SS DED) and 70 DED patients with pSS (SS DED). We graded MMP-9 expression in InflammaDry® (Quidel, San Diego, CA, USA) using a 5-scale grading system and dichotomous grading systems with four different cut-off grades (D1 to D4 systems). The only DED parameter that showed a significant correlation with the 5-scale grading method was tear osmolarity (Tosm). In both groups, subjects with positive MMP-9 had lower tear secretion and higher Tosm than those with negative MMP-9 according to the D2 dichotomous system. Tosm determined D2 positivity at cutoffs > 340.5 and > 317.5 mOsm/L in the Non-SS DED and SS DED groups, respectively. Tear secretion < 10.5 mm or tear break-up time < 5.5 s stratified D2 positivity in the Non-SS DED group. In conclusion, the dichotomous grading system of InflammaDry reflects ocular surface indices better than the 5-scale grading system and may be more practical in real clinical circumstances.
Subject(s)
Dry Eye Syndromes , Lacerations , Humans , Matrix Metalloproteinase 9/metabolism , Point-of-Care Systems , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/metabolism , Tears/metabolism , ImmunoassayABSTRACT
The indoor environment has been recognized as a crucial factor that can influence health and wellbeing of occupants. This is particularly true in hospital settings, where various environmental attributes can significantly affect patients' recovery and staff members' productivity. The present study aimed to investigate how occupants in hospitals perceived indoor environment, focusing specifically on COVID-19 hospitals across Republic of Korea. The study recruited two groups of participants: patients (n = 100) who had been hospitalized in COVID-19 hospitals and staff members (n = 103) who worked in COVID-19 hospitals. The data collected from the participants were analyzed using multiple regression models to determine which environmental attributes significantly affected their perception of the indoor environment. The study revealed that satisfaction with indoor acoustic environment and odor were significant predictors for how patients perceived the indoor environment as helpful for their recovery from COVID-19. On the other hand, odor was also the significant factor affecting staff members' perceived helpfulness for work. The results suggested that different environmental attributes can have a significant impact on the perception of the indoor environment, depending on the characteristics of occupancy. The study's findings provided insights into the certain environmental factors that COVID-19 hospitals can prioritize. These insights can help policymakers and hospital administrators to develop strategies to create hospital environments that meet the needs of both groups. The study also suggested that further research is needed to investigate additional factors affecting occupants' perception of the indoor environment in hospital settings.
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has had a major influence on working patterns worldwide, given the various lockdown periods and the shift to remote working. As people's noise perception is known to be closely linked with their work performance and job satisfaction, investigating the noise perception in indoor spaces, especially in situations where people work from home, is crucial; however, studies on this aspect are limited. Thus, here, this study aimed to investigate the relationship between indoor noise perception and remote work during the pandemic. The study assessed how people who worked from home perceived indoor noise, and how it related with their work performance and job satisfaction. A social survey was conducted with respondents who worked from home during the pandemic in South Korea. A total of 1,093 valid responses were used for data analysis. Structural equation modeling was used as a multivariate data analysis method to simultaneously estimate multiple and interrelated relationships. The results showed that indoor noise disturbance significantly affected annoyance and work performance. Annoyance with indoor noise affected job satisfaction. Job satisfaction was found to have a significant impact on work performance, particularly on two dimensions of the work performance that are crucial for achieving organizations' goals. Moreover, one dimension of the work performance had a significant impact on annoyance. The study proposed that reducing negative perception of indoor noise and improvement of job satisfaction can lead to the maximization of one's work performance when working from home.
Subject(s)
COVID-19 , Pandemics , Humans , Teleworking , COVID-19/epidemiology , Communicable Disease Control , Perception , Job SatisfactionABSTRACT
This study aimed to investigate the impact of ocular demodicosis on dry eye disease (DED) and meibomian gland dysfunction (MGD) across different age populations: young (20 to < 40), middle-aged (40 to < 60), and elderly (≥ 60), based on the retrospective medical chart review. In each age subgroup, Demodex infestation and its count were correlated with clinical parameters of DED and MGD. Among the total of 351 subjects, 52.7% had ocular demodicosis, with a mean of 2.31 ± 1.39 mites per four eyelashes (0.58 per lash) in a unilateral eye. In the age subgroup 1 (age < 40; N = 44), subjects with Demodex had significantly higher meibum quality grades. In subgroup 2 (40 ≤ age < 60; N = 122), subjects with Demodex had higher ocular surface disease index scores and higher MG expressibility grades. However, in subgroup 3 (age ≥ 60; N = 185), demographics and all parameters did not differ according to Demodex infestation. Moreover, the number of mites did not correlate with MGD severity in any of the subgroups. In conclusion, age may act as a significant confounding factor in the relationship between ocular Demodex infestation and clinical features of DED and MGD, despite older patients aged 60 years and above being at a higher risk of Demodex infestation and experiencing more severe MGD.
Subject(s)
Dry Eye Syndromes , Eye Infections, Parasitic , Meibomian Gland Dysfunction , Mite Infestations , Mites , Animals , Aged , Middle Aged , Humans , Mite Infestations/complications , Mite Infestations/epidemiology , Retrospective Studies , Meibomian GlandsABSTRACT
PRCIS: Although Omidenepag isopropyl drops elicited stable intraocular pressure reductions in NTG patients, transient changes in refraction and corneal endothelial cells, significant increase of central corneal thickness, and corneal erosion should be considered. PURPOSE: To analyze the efficacy and safety of 0.002% omidenepag Isopropyl (OMDI) eye drops in patients with normal tension glaucoma (NTG). METHODS: Medical records for 62 eyes treated with OMDI for ≥6 months were analyzed. Intraocular pressure (IOP), refraction, keratometry, central corneal thickness (CCT), endothelial cell count, coefficient of variation of endothelial cell area (CV), corneal erosion, and central retinal thickness were compared at baseline and 1, 3, and 6 months. RESULTS: IOP significantly decreased from 13.4±3.8 to 11.9±3.0, 11.7±2.9, and 12.2±3.3 mm Hg at each follow-up ( P <0.001). Endothelial cell count did not change, but CV transiently increased from 12.6 to 17.0 at 1 month, CCT increased from 531.5 to 538.4 µm, myopia changed from -1.5 to -1.9 D, and keratometry changed from 44.5 to 44.7 D. CV, myopia, and keratometry recovered to baseline at 6 months; however, CCT remained high. Significant corneal erosion was observed at 6 months. Central retinal thickness changes were not observed. There were improvements in prostaglandin-associated skin pigmentation (86.7%), eyelash elongation (40.0%), and deepening of the upper eyelid sulcus and ptosis (~30%) at 3 months after exchange to OMDI. Adverse reactions were corneal erosion (27.4%), corneal thickening (21.0%), conjunctival hyperemia (11.3%), photophobia (5.7%), blurred vision (5.7%), and anterior chamber cells (4.8%). CONCLUSIONS: OMDI eye drops elicited significant and stable IOP reductions after 6 months in NTG patients with low IOP. However, transient myopic and corneal endothelial cell changes, development of corneal thickening, and corneal erosion should be considered when using OMDI.