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1.
Rom J Ophthalmol ; 68(2): 191-197, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006336

RESUMO

Lacrimal gland lymphomas are rare orbital tumors, constituting a minor fraction of all orbital and ocular adnexal malignancies. This case study presents an 83-year-old male with bilateral lacrimal gland tumors, more prominent in the left orbit, causing decreased visual acuity, red eye, excessive tearing, and diplopia. Initial ophthalmological evaluations and imaging suggested bilateral lacrimal gland lymphoma, confirmed by histopathology as diffuse large B-cell non-Hodgkin lymphoma of the MALT type. Due to the significant tumor size and risk of visual function loss, surgical intervention was performed, followed by corticosteroid therapy. Postoperatively, a marked improvement in symptoms and a reduction in tumor size were observed. This case underscores the importance of comprehensive diagnostic approaches, including clinical, imaging, and histopathological evaluations, highlighting the need for a multidisciplinary approach in managing rare orbital tumors like lacrimal gland lymphoma. The patient's postoperative and follow-up care included oncological management to monitor and ensure long-term disease control and patient well-being. Abbreviations: RE = right eye, LE = left eye, CT = Computer tomography, MRI = Magnetic Resonance Imaging, TOD = intraocular pressure of right eye, TOS = intraocular pressure of left eye, US = ultrasound.


Assuntos
Doenças do Aparelho Lacrimal , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Humanos , Masculino , Idoso de 80 Anos ou mais , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/cirurgia , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/cirurgia , Neoplasias Oculares/terapia , Aparelho Lacrimal/patologia , Aparelho Lacrimal/cirurgia , Aparelho Lacrimal/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/cirurgia , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/cirurgia , Acuidade Visual , Procedimentos Cirúrgicos Oftalmológicos/métodos , Biópsia
2.
Medicine (Baltimore) ; 103(28): e38784, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996104

RESUMO

Ocular surface homeostasis plays a vital role in maintaining of eye health. Dry eye disease is one of the prominent and typical manifestations of disruption of ocular surface homeostasis that leads to the worsening of ocular surface homeostasis that leads to the worsening of ocular surface disease when it interacts with other pathogenic factors. However, disruption in ocular surface homeostasis in children is often overlooked because of the current methods of assessing ocular surface homeostasis. This review summarizes the main factors affecting ocular surface homeostasis in children, with the aim of drawing the attention of clinicians to the disruption of ocular surface homeostasis in children when dealing with such diseases. Ocular surface homeostasis involves several interrelated components, each of which plays a nonnegligible role in ocular surface homeostasis. Unlike adults, children have a stronger lacrimal gland secretion capacity and milder symptoms when there is a slight disruption of the ocular surface homeostasis. In addition, children's expressive abilities were weaker. Therefore, dry eye in children is often ignored by doctors and parents, and clinicians should pay more attention to the protection of ocular surface homeostasis when treating children with these diseases. Therefore, there is a need for diagnostic criteria for dry eye disease specific to children.


Assuntos
Síndromes do Olho Seco , Homeostase , Humanos , Homeostase/fisiologia , Criança , Síndromes do Olho Seco/terapia , Síndromes do Olho Seco/fisiopatologia , Síndromes do Olho Seco/etiologia , Lágrimas/metabolismo , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/fisiopatologia
3.
Invest Ophthalmol Vis Sci ; 65(8): 26, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39017634

RESUMO

Purpose: CD25KO mice are a model of Sjögren disease (SjD) driven by autoreactive T cells. Cathepsin S (CTSS) is a protease crucial for major histocompatibility complex class II presentation that primes T cells. We investigated if a diet containing CTSS inhibitor would improve autoimmune signs in CD25KO mice. Methods: Four-week female CD25KO mice were randomly chosen to receive chow containing a CTSS inhibitor (R05461111, 262.5 mg/kg chow) or standard chow for 4 weeks. Cornea sensitivity was measured. Inflammatory score was assessed in lacrimal gland (LG) histologic sections. Flow cytometry of LG and ocular draining lymph nodes (dLNs) investigated expression of Th1 and Th17 cells. Expression of inflammatory, T- and B-cell, and apoptotic markers in the LG were assessed with quantitative PCR. The life span of mice receiving CTSS inhibitor or standard chow was compared. CD4+ T cells from both groups were isolated from spleens and adoptively transferred into RAG1KO female recipients. Results: Mice receiving CTSS inhibitor had better cornea sensitivity and improved LG inflammatory scores. There was a significant decrease in the frequency of CD4+ immune cells and a significant increase in the frequency of CD8+ immune cells in the dLNs of CTSS inhibitor mice. There was a significant decrease in Th1 and Th17 cells in CTSS inhibitor mice in both LGs and dLNs. Ifng, Ciita, and Casp8 mRNA in CTSS inhibitor mice decreased. Mice that received the CTSS inhibitor lived 30% longer. Adoptive transfer recipients with CTSS inhibitor-treated CD4+ T cells had improved cornea sensitivity and lower inflammation scores. Conclusions: Inhibiting CTSS could be a potential venue for the treatment of SjD in the eye and LG.


Assuntos
Catepsinas , Modelos Animais de Doenças , Citometria de Fluxo , Aparelho Lacrimal , Camundongos Knockout , Síndrome de Sjogren , Animais , Camundongos , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/tratamento farmacológico , Feminino , Catepsinas/antagonistas & inibidores , Catepsinas/metabolismo , Catepsinas/genética , Aparelho Lacrimal/patologia , Aparelho Lacrimal/metabolismo , Camundongos Endogâmicos C57BL , Transferência Adotiva , Células Th17/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Células Th1/imunologia , Subunidade alfa de Receptor de Interleucina-2
4.
PLoS One ; 19(7): e0305717, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38959275

RESUMO

BACKGROUND: The present study reviewed the clinicopathological features and outcomes of bilateral lacrimal gland lesions. METHODS: The data of 113 patients who underwent lacrimal gland biopsy at the West China Hospital of Sichuan University, China, between January 1, 2010, and December 31, 2021, are presented in this case series. The patients all presented with bilateral lacrimal gland lesions. The collected data included patient demographics, clinical features, the results of laboratory examinations, imaging presentations, histopathological diagnoses, treatments, and outcomes. RESULTS: The mean age of the 113 enrolled patients was 47.4 ± 14.9 years (range, 11-77 years) with a predominance of females (54.9%, n = 62). The lacrimal gland was the source of the majority of biopsy tissue (98.2%, n = 111). The most prevalent etiology was immunoglobulin G4-related ophthalmic disease (IgG4-ROD) (32.7%, n = 37), followed by idiopathic orbital inflammation (IOI) (28.3%, n = 32), mucosa-associated lymphoid tissue (MALT) lymphoma (17.7%, n = 20), reactive lymphoid hyperplasia (RLH) (10.6%, n = 12), and mantle cell lymphoma (4.4%, n = 5). Patients with IOI were significantly younger than those with IgG4-ROD and MALT lymphoma (t = 2.932, P = 0.005; t = 3.865, P<0.001, respectively). Systemic symptoms were more prevalent among patients with IgG4-ROD (χ2 = 7.916, P = 0.005). The majority of patients were treated with surgery (53.1%, n = 60), with surgery combined with corticosteroid therapy (21.2%, n = 24) being the second most common treatment. The majority of patients (91.2%, n = 103) attained complete resolution, stable disease, or significant improvement. CONCLUSION: In conclusion, there are several aetiologies associated with bilateral lacrimal gland lesions, the most prevalent being IgG4-ROD, IOI, and MALT lymphoma. Systemic symptoms were more common in patients with IgG4-ROD. The majority of patients who presented with bilateral lesions of the lacrimal glands responded satisfactorily to treatment, with favorable results.


Assuntos
Doenças do Aparelho Lacrimal , Aparelho Lacrimal , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Aparelho Lacrimal/patologia , Criança , Adulto Jovem , Doenças do Aparelho Lacrimal/patologia , Estudos Retrospectivos , Biópsia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , China/epidemiologia , Resultado do Tratamento , Doença Relacionada a Imunoglobulina G4/patologia , Doença Relacionada a Imunoglobulina G4/complicações
5.
Zhonghua Yan Ke Za Zhi ; 60(7): 623-624, 2024 Jul 11.
Artigo em Chinês | MEDLINE | ID: mdl-38955764

RESUMO

A 35-year-old female presented with a chief complaint of exudates from the outer corner of the left eye for more than half a year after cosmetic lateral canthoplasty. A fistula was seen in the skin of the left eye 5 mm from the lateral canthus, with clear fluid inside it. Left eyelid fistula was diagnosed and surgically removed. The histopathological examination confirmed that the tissue connected with the fistula was lacrimal gland tissue. No recurrence was found during the 2-month follow-up.


Assuntos
Pálpebras , Humanos , Feminino , Adulto , Pálpebras/cirurgia , Doenças Palpebrais/etiologia , Doenças Palpebrais/cirurgia , Aparelho Lacrimal/cirurgia , Blefaroplastia/efeitos adversos , Blefaroplastia/métodos , Fístula/etiologia , Fístula/cirurgia , Complicações Pós-Operatórias/etiologia
6.
Invest Ophthalmol Vis Sci ; 65(6): 1, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829671

RESUMO

Purpose: Loss of function of the lacrimal gland (LG), which produces the aqueous tear film, is implicated in age-related dry eye. To better understand this deterioration, we evaluated changes in lipid metabolism and inflammation in LGs from an aging model. Methods: LG sections from female C57BL/6J mice of different ages (young, 2-3 months; intermediate, 10-14 months; old,  ≥24 months) were stained with Oil Red-O or Toluidine blue to detect lipids. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis and western blotting of LG lysates determined differences in the expression of genes and proteins related to lipid metabolism. A photobleaching protocol to quench age-related autofluorescence was used in LG sections to evaluate changes in immunofluorescence associated with NPC1, NPC2, CTSL, and macrophages (F4/80, CD11b) with age using confocal fluorescence microscopy. Results: Old LGs showed increased lipids prominent in basal aggregates in acinar cells and in extra-acinar sites. LG gene expression of Npc1, Npc2, Lipa, and Mcoln2, encoding proteins involved in lipid metabolism, was increased with age. NPC1 was also significantly increased in old LGs by western blotting. In photobleached LG sections, confocal fluorescence microscopy imaging of NPC1, NPC2, and CTSL immunofluorescence showed age-associated enrichment in macrophages labeled to detect F4/80. Although mononuclear macrophages were detectable in LG at all ages, this novel multinucleate macrophage population containing NPC1, NPC2, and CTSL and enriched in F4/80 and some CD11b was increased with age at extra-acinar sites. Conclusions: Lipid-metabolizing proteins enriched in F4/80-positive multinucleated macrophages are increased in old LGs adjacent to sites of lipid deposition in acini.


Assuntos
Envelhecimento , Western Blotting , Aparelho Lacrimal , Metabolismo dos Lipídeos , Macrófagos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Animais , Feminino , Envelhecimento/fisiologia , Camundongos , Metabolismo dos Lipídeos/fisiologia , Macrófagos/metabolismo , Aparelho Lacrimal/metabolismo , Microscopia Confocal , Modelos Animais de Doenças , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia
7.
Int Ophthalmol ; 44(1): 271, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38914728

RESUMO

OBJECTIVE: This research conducted a comprehensive evaluation of the effectiveness of ultrasonic elastography (USE) in detecting lacrimal gland involvement in individuals suffering from primary Sjögren's syndrome (pSS). METHODS: A comprehensive search was undertaken across multiple databases including PubMed, the Cochrane Library, EMBASE, Wanfang, Web of Science, and the Chinese National Knowledge Infrastructure, to gather relevant literature pertaining to the application of USE in diagnosing pSS from January 1, 2000, to October 1, 2023. Pooled data were used to calculate sensitivity, specificity, and diagnostic odds ratios. Several summary metrics were used to evaluate SWE's performance in detecting pSS, including the area under the receiver operating characteristic curve, diagnostic odds ratios, sensitivities, and specificities. RESULTS: Five pertinent studies included a total of 273 patients. Shear wave elastography (SWE) demonstrated a pooled sensitivity of 0.88 (95% CI 0.77-0.94) and specificity of 0.94 (95% CI 0.88-0.98), with an area under the receiver operating characteristic curve of 0.97 (95% CI 0.95-0.98). SWE exhibited a positive likelihood ratio of 15.86 (95% CI 6.99-36.00) and a negative likelihood ratio of 0.13 (95% CI 0.07-0.25). No evidence of publication bias was observed (p = 0.70). CONCLUSION: SWE demonstrates a remarkable degree of precision in detecting lacrimal gland involvement in individuals suffering from pSS.


Assuntos
Técnicas de Imagem por Elasticidade , Aparelho Lacrimal , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Aparelho Lacrimal/diagnóstico por imagem , Curva ROC
8.
Int Ophthalmol ; 44(1): 257, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38909080

RESUMO

PURPOSE: The most prevalent lacrimal apparatus dysfunctions associated with differentiated thyroid cancer(DTC) after I-131 therapy are dry eye and nasolacrimal duct obstruction(NLDO), leading to ocular discomfort and lower quality of life for patients. It is crucial to diagnose and manage lacrimal apparatus dysfunction associated with I-131 therapy for DTC. Therefore, this review aims to comprehensively summarize and analyze the advances in mechanisms and therapeutic options underlying lacrimal apparatus dysfunction induced by I-131 therapy for DTC. METHODS: A comprehensive search of CNKI, PubMed, and Wed of Science was performed from the database to December of 2023. Key search terms were "Thyroid cancer", "I-131", "Complications", "Dry eye", "Epiphora", "Tear", "Nasolacrimal duct" and "NLDO". RESULTS: The research indicates that I-131 therapy for DTC causes damage to the lacrimal glands and nasolacrimal duct system, resulting in symptoms such as dry eye, epiphora, and mucoid secretions. Moreover, recent research has focused on exploring relevant risk factors of the condition and experimental and clinical treatments. However, there is some controversy regarding the mechanisms involved, whether it is due to the passive flow of I-131 in tears, active uptake of I-131 by the sodium-iodide symporter (NIS) in the lacrimal sac and nasolacrimal duct, or secondary metabolic and hormonal disturbances caused by I-131. CONCLUSION: It is crucial for early detection and preventive measures by ophthalmologists and the need for further studies to elucidate the mechanisms underlying the disease.


Assuntos
Radioisótopos do Iodo , Doenças do Aparelho Lacrimal , Aparelho Lacrimal , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Doenças do Aparelho Lacrimal/etiologia , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/fisiopatologia , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/fisiopatologia , Lesões por Radiação/etiologia , Lesões por Radiação/diagnóstico , Lesões por Radiação/fisiopatologia , Qualidade de Vida , Ducto Nasolacrimal/efeitos da radiação
9.
J. optom. (Internet) ; 17(2): [100488], Abr-Jun, 2024. tab, graf
Artigo em Inglês | IBECS | ID: ibc-231623

RESUMO

Purpose: As ocular dryness and glaucoma are more prevalent with increasing age, understanding how the tear film affects tonometry is important. The present study aims to understand the impact that changes in the tear film have on intraocular pressure (IOP), corneal hysteresis, and corneal resistance factor measurements. Methods: Cross-sectional research was conducted and 37 patients were assessed. The tear film lipid layer and the non-invasive break-up time (NIBUT) were evaluated using the Tearscope Plus (Keeler, Windsor, UK). Dry eye symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. IOP was measured using rebound tonometry and the Ocular Response Analyzer (ORA, Reichert). Corneal biomechanical properties were measured using ORA. Results: It was found that an increase in the IOP measured with the iCare was directly correlated with the subclass that evaluated symptomatology associated with environmental factors (r = 0.414, p<0.05, Spearman). Goldmann-correlated IOP (IOPg) and Corneal-compensated IOP (IOPcc) values were statistically significantly different between the various interferometric patterns (p<0.05). It was also found that an increase in the corneal biomechanical properties measured with ORA was directly correlated with the overall scores obtained when using the OSDI and some of its subclasses. Conclusions: Tear film interferometric patterns were shown to have some impact on the IOP measured using ORA. The IOP measured with iCare seems to be related to the symptomatology obtained from OSDI. Corneal biomechanical properties were related to the OSDI total score and some of its subclasses. An increase in symptomatology was associated with an increase in the measured biomechanical properties of the cornea.(AU)


Assuntos
Humanos , Masculino , Feminino , Optometria , Aparelho Lacrimal , Visão Ocular , Síndromes do Olho Seco , Glaucoma , Pressão Intraocular
10.
Exp Eye Res ; 244: 109937, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782179

RESUMO

Sjögren's syndrome (SS) dry eye can cause ocular surface inflammation and lacrimal gland (LG) damage, leading to discomfort and potential vision problems. The existing treatment options for SS dry eye are currently constrained. We investigated the possible therapeutic effect and the underlying mechanism of AS101 in autoimmune dry eye. AS101 was injected subconjunctivally into a rabbit model of autoimmune dacryoadenitis and its therapeutic effects were determined by evaluating clinical and histological scores. The expressions of effector T cells (Teff)/regulatory T cells (Treg)-related transcription factors and cytokines, inflammation mediators, and transcription factor NFATc2 were measured by quantitative real-time PCR and/or Western blot both in vivo and in vitro. Additionally, the role of NFATc2 in the immunomodulatory effects of AS101 on T cells was explored by co-culturing activated peripheral blood lymphocytes (PBLs) transfected with NFATc2 overexpression lentiviral plasmid with AS101. AS101 treatment potently ameliorated the clinical severity and reduced the inflammation of LG. Further investigation revealed that AS101 treatment led to decreased expression of Th1-related genes (T-bet and IFN-γ) and Th17-related genes (RORC, IL-17A, IL-17F, and GM-CSF) and increased expression of Treg-related gene Foxp3 in vivo and in vitro. Meanwhile, AS101 suppressed the expression of TNF-α, IL-1ß, IL-23, IL-6, MMP-2, and MMP-9. Mechanistically, AS101 downregulated the expression of NFATc2 in inflamed LGs. Overexpression of NFATc2 in activated PBLs partially blunted the effect of AS101 on Teff suppression and Treg promotion. In conclusion, AS101 is a potential regulator of Teff/Treg cell balance and could be an effective treatment agent for SS dry eye.


Assuntos
Dacriocistite , Fatores de Transcrição NFATC , Síndrome de Sjogren , Animais , Feminino , Coelhos , Doenças Autoimunes/imunologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/metabolismo , Western Blotting , Citocinas/metabolismo , Dacriocistite/tratamento farmacológico , Dacriocistite/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Fatores de Transcrição NFATC/metabolismo , Fatores de Transcrição NFATC/genética , Reação em Cadeia da Polimerase em Tempo Real , Linfócitos T Reguladores/imunologia , Síndrome de Sjogren/tratamento farmacológico
11.
Clin Immunol ; 264: 110260, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788885

RESUMO

Sjögren's disease (SjD) is a chronic autoimmune disease characterized by focal lymphocytic inflammation in lacrimal and salivary glands. We recently identified IL-27 as a requisite signal for the spontaneous SjD-like manifestations in nonobese diabetic (NOD) mice. Here, we define T cell-intrinsic effects of IL-27 in lacrimal gland disease in NOD mice. IL-27 receptor was required by both CD4 T effector (Te) cells and CD8 T cells to mediate focal inflammation. Intrinsic IL-27 signaling was associated with PD-1 and ICOS expressing T follicular helper (Tfh)-like CD4 Te cells within lacrimal glands, including subsets defined by CD73 or CD39 expression. CD8 T cells capable of IL-27 signaling also expressed PD-1 with subsets expressing ICOS and CD73 demonstrating a T follicular cytotoxic (Tfc)-like cell phenotype and others expressing a CD39hi exhausted-like phenotype. These findings suggest IL-27 is a key early signal driving a follicular-type response in lacrimal gland inflammation in NOD mice.


Assuntos
Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Aparelho Lacrimal , Camundongos Endogâmicos NOD , Síndrome de Sjogren , Animais , Síndrome de Sjogren/imunologia , Camundongos , Linfócitos T CD8-Positivos/imunologia , Aparelho Lacrimal/imunologia , Aparelho Lacrimal/patologia , Interleucinas/imunologia , Interleucinas/metabolismo , Linfócitos T CD4-Positivos/imunologia , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Feminino , Transdução de Sinais/imunologia , Receptores de Interleucina/imunologia , Interleucina-27/metabolismo , Interleucina-27/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Apirase/imunologia , Apirase/metabolismo
12.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 111-118, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38814228

RESUMO

Bioinformatics analysis was performed to reveal the underlying pathogenesis of type 2 diabetes (T2DM) dry eye(DE) and to predict the core targets and potential pathways for electroacupuncture (EA) treatment of T2DM DE, in which key targets such as Toll-likereceptor4 (TLR4), NF-κB and Tumor necrosis factor-α (TNF-α) may be involved. Next, streptozotocin and a high-fat diet were used to generate T2DM-DE rats. Randomly picked EA, fluorometholone, model, and sham EA groups were created from successfully modelled T2DM DE rats. Six more rats were chosen as the blank group from among the normal rats. The results of DE index showed that EA improved the ocular surface symptoms.HE staining showed that EA attenuated the pathological changes in the cornea, conjunctiva and lacrimal gland of T2DM DE rats. EA decreased the expression of TLR4, MyD88, P-NF-κB P65, and TNF-α in the cornea, conjunctiva, and lacrimal gland, in accordance with immunofluorescence and Western blot data. Thus, EA reduced ocular surface symptoms and improved pathological changes of cornea, conjunctiva, and lacrimal gland induced by T2DM DE inT2DM DE rats, and the mechanism may be related to the inhibition of overactivation of the TLR4/NF-κB signaling pathway by EA and thus attenuating ocular surface inflammation.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Síndromes do Olho Seco , Eletroacupuntura , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Animais , Receptor 4 Toll-Like/metabolismo , Eletroacupuntura/métodos , NF-kappa B/metabolismo , Síndromes do Olho Seco/terapia , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Ratos Sprague-Dawley , Ratos , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Córnea/patologia , Córnea/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo
13.
Ocul Surf ; 33: 64-73, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38705236

RESUMO

PURPOSE: Polyunsaturated fatty acids (PUFA) are a source of bioactive lipids regulating inflammation and its resolution. METHODS: Changes in PUFA metabolism were compared between lacrimal glands (LGs) from young and aged C57BL/6 J mice using a targeted lipidomics assay, as was the gene expression of enzymes involved in the metabolism of these lipids. RESULTS: Global reduction in PUFAs and their metabolites was observed in aged LGs compared to young controls, averaging between 25 and 66 % across all analytes. ꞷ-6 arachidonic acid (AA) metabolites were all reduced in aged LGs, where the changes in prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) were statistically significant. Several other 5-lipoxygenase (5-LOX) mediated metabolites were significantly reduced in the aged LGs, including D-series resolvins (e.g., RvD4, RvD5, and RvD6). Along with the RvDs, several ꞷ-3 docosahexaenoic acid (DHA) metabolites such as 14-HDHA, neuroprotectin D1 (NPD1), Maresin 2 (MaR2), and MaR 1 metabolite (22-COOH-MaR1) were significantly reduced in aged LGs. Similarly, ꞷ-3 eicosapentaenoic acid (EPA) and its metabolites were significantly reduced in aged LGs, where the most significantly reduced was 18-HEPE. Using metabolite ratios (product:precursor) for specific metabolic conversions as surrogate enzymatic measures, reduced 12-LOX activity was identified in aged LGs. CONCLUSION: In this study, global reduction of PUFAs and their metabolites was found in the LGs of aged female C57BL/6 J compared to young controls. A consistent reduction was observed across all detected lipid analytes except for ꞷ-3 docosapentaenoic acid (DPA) and its special pro-resolving mediator (SPM) metabolites in aged mice, suggesting an increased risk for LG inflammation.


Assuntos
Envelhecimento , Ácidos Graxos Insaturados , Aparelho Lacrimal , Camundongos Endogâmicos C57BL , Animais , Camundongos , Ácidos Graxos Insaturados/metabolismo , Envelhecimento/metabolismo , Aparelho Lacrimal/metabolismo , Metabolismo dos Lipídeos/fisiologia , Feminino , Lipidômica/métodos
14.
Ocul Surf ; 33: 50-63, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38703817

RESUMO

PURPOSE: To investigate the global transcriptional landscape of lacrimal gland cell populations in the GVHD mouse model. METHODS: Single-cell RNA sequencing and further bioinformatic analysis of dissociated lacrimal gland (LG) cells from the mouse model were performed. Parts of transcriptional results were confirmed by immunofluorescence staining. RESULTS: We identified 23 cell populations belonging to 11 cell types. In GVHD LG, the proportion of acinar cells, myoepithelial cells, and endothelial cells was remarkably decreased, while T cells and macrophages were significantly expanded. Gene expression analysis indicated decreased secretion function, extracellular matrix (ECM) synthesis, and increased chemokines of myoepithelial cells. A newly described epithelial population named Lrg1high epithelial cells, expressing distinct gene signatures, was exclusively identified in GVHD LG. The fibroblasts exhibited an inflammation gene pattern. The gene pattern of endothelial cells suggested an increased ability to recruit immune cells and damaged cell-cell junctions. T cells were mainly comprised of Th2 cells and effective memory CD8+ T cells. GVHD macrophages exhibited a Th2 cell-linked pattern. CONCLUSIONS: This single-cell atlas uncovered alterations of proportion and gene expression patterns of cell populations and constructed cell-cell communication networks of GVHD LG. These data may provide some new insight into understanding the development of ocular GVHD.


Assuntos
Modelos Animais de Doenças , Doença Enxerto-Hospedeiro , Aparelho Lacrimal , Animais , Camundongos , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/metabolismo , Análise de Célula Única/métodos , Camundongos Endogâmicos C57BL , Análise de Sequência de RNA/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Camundongos Endogâmicos BALB C
15.
Exp Eye Res ; 244: 109949, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38815791

RESUMO

PURPOSE: The current study used various techniques to develop a rabbit animal model of lacrimal gland damage caused by scarring conjunctivitis in the periglandular area. METHODS: Left eyes of New Zealand white rabbits were injected with 0.1 ml of 1M NaOH subconjunctivally around superior and inferior lacrimal gland orifices (Group 1, n = 4), touched with 1M NaOH for 100 s to the superior and inferior fornices with conjunctival denuding (Group 2; n = 4), and electrocauterization to the ductal opening area (Group 3; n = 4). The ocular surface staining, Schirmer I, lacrimal gland, and conjunctival changes were observed at baseline,1, 4, 8, and 12 weeks. The degree of glandular inflammation, conjunctival fibrosis (Masson Trichrome), and goblet cell density (PAS) were also assessed. RESULTS: At 12 weeks, the lacrimal glands of group 1 rabbits with periglandular injection showed severe inflammation with mean four foci/10HPF and a significant mean reduction in the Schirmer values by 7.6 mm (P = 0.007). Lacrimal glands had diffuse acinar atrophy, loss of myoepithelial cells, and ductular dilatation. The overlying conjunctiva showed fibrosis, goblet cell loss, and corneal vascularization in the inferotemporal quadrant. No lacrimal gland or ocular surface changes were observed in groups 2 and 3 at 12 weeks, except for localized subconjunctival fibrosis. CONCLUSION: Periglandular injection of 0.1 ml of 1M NaOH induced extensive lacrimal gland damage with reduced secretion and scarring in the subconjunctival plane compared to direct cauterization or direct NaOH contact to the ductal orifices of the rabbit lacrimal gland.


Assuntos
Cicatriz , Túnica Conjuntiva , Conjuntivite , Modelos Animais de Doenças , Síndromes do Olho Seco , Células Caliciformes , Lágrimas , Animais , Coelhos , Síndromes do Olho Seco/metabolismo , Cicatriz/patologia , Células Caliciformes/patologia , Túnica Conjuntiva/patologia , Lágrimas/metabolismo , Conjuntivite/patologia , Aparelho Lacrimal/patologia , Hidróxido de Sódio/toxicidade , Fibrose , Masculino , Contagem de Células , Feminino , Eletrocoagulação
16.
Int Ophthalmol ; 44(1): 224, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744721

RESUMO

BACKGROUND: The pigtail was used to create an opening at the lower punctal site in grade 0 stenosis with insertion of self-retaining tube and Mitomycin C (MMC). METHODS: The patients with acquired lower punctal stenosis (grade 0) were divided randomly into equal groups, Group A: were treated with pigtail and MMC 0.02% and Group B: were treated with pigtail alone. The pigtail was inserted through the upper punctum until its tip reached the occluded punctum, this site was incised with a scalpel (No. 11). A self-retaining bicanalicular tube was then placed. RESULTS: Results of 36 eyes from 26 patients were included. No differences were observed between both groups regarding epiphora score, FDD test and punctal size preoperatively. The postoperative epiphora score, there were significant differences at 1 month (P = 0.035), 3 months (P = 0.005), and 6 months after removal (P < 0.001). The FDD test, there were significant differences at 6 months (P = 0.045), 1 month (P = 0.021), 3 months (P = 0.012), and 6 months post tube removal (P = 0.005). The punctal size, both groups differed at 1 month (P = 0.045), 3 months (P = 0.03), and 6 months post tube removal (P = 0.005). Only one case (5.5%) at each group showed extrusion of the tube. CONCLUSION: The pigtail probe, bicanalicular stent and MMC can be an effective method in treatment of severe punctal stenosis.


Assuntos
Intubação , Obstrução dos Ductos Lacrimais , Mitomicina , Humanos , Mitomicina/administração & dosagem , Masculino , Feminino , Obstrução dos Ductos Lacrimais/terapia , Obstrução dos Ductos Lacrimais/diagnóstico , Pessoa de Meia-Idade , Intubação/métodos , Intubação/instrumentação , Idoso , Resultado do Tratamento , Dacriocistorinostomia/métodos , Aparelho Lacrimal/cirurgia , Adulto , Seguimentos , Stents , Estudos Prospectivos , Alquilantes/administração & dosagem
17.
Exp Biol Med (Maywood) ; 249: 10175, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756167

RESUMO

Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) and the structures responsible for maintaining tear homeostasis, is not completely known. It has been shown that the Opioid Growth Factor Receptor (OGFr), and its ligand, Opioid Growth Factor (OGF), is dysregulated in the ocular surface of diabetic rats leading to overproduction of the inhibitory growth peptide OGF. The opioid antagonist naltrexone hydrochloride (NTX) blocks the OGF-OGFr pathway, and complete blockade following systemic or topical treatment with NTX restores the rate of re-epithelialization of corneal epithelial wounds, normalizes corneal sensitivity, and reverses dry eye in diabetic animal models. These effects occur rapidly and within days of initiating treatment. The present study was designed to understand mechanisms related to the fast reversal (<5 days) of dry eye by NTX in type 1 diabetes (T1D) by investigating dysregulation of the LFU. The approach involved examination of the morphology of the LFU before and after NTX treatment. Male and female adult Sprague-Dawley rats were rendered hyperglycemic with streptozotocin, and after 6 weeks rats were considered to be a T1D model. Rats received topical NTX twice daily to one eye for 10 days. During the period of treatment, tear production and corneal sensitivity were recorded. On day 11, animals were euthanized and orbital tissues including conjunctiva, eyelids, and lacrimal glands, were removed and processed for histologic examination including immunohistochemistry. Male and female T1D rats had significantly decreased tear production and corneal insensitivity, significantly decreased number and size of lacrimal gland acini, decreased expression of aquaporin-5 (AQP5) protein and decreased goblet cell size. Thus, 10 days of NTX treatment restored tear production and corneal sensitivity to normal values, increased AQP5 expression, and restored the surface area of goblet cells to normal. NTX had no effect on the number of lacrimal gland acini or the number of conjunctival goblet cells. In summary, blockade of the OGF-OGFr pathway with NTX reversed corneal and lacrimal gland complications and restored some components of tear homeostasis confirming the efficacy of topical NTX as a treatment for ocular defects in diabetes.


Assuntos
Aquaporina 5 , Diabetes Mellitus Experimental , Aparelho Lacrimal , Naltrexona , Lágrimas , Animais , Masculino , Ratos , Administração Tópica , Aquaporina 5/metabolismo , Diabetes Mellitus Experimental/complicações , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/patologia , Síndromes do Olho Seco/metabolismo , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/efeitos dos fármacos , Aparelho Lacrimal/patologia , Naltrexona/farmacologia , Ratos Sprague-Dawley , Lágrimas/metabolismo , Lágrimas/efeitos dos fármacos
18.
Ann Anat ; 255: 152272, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38697581

RESUMO

The ocular system is in constant interaction with the environment and with numerous pathogens. The ATP-binding cassette (ABC) transporters represent one of the largest groups among the transmembrane proteins. Their relevance has been demonstrated for their defense function against biotic and abiotic stress factors, for metabolic processes in tumors and for their importance in the development of resistance to drugs. The aim of this study was to analyze which ABC transporters are expressed at the ocular surface and in the human lacrimal apparatus. Using RT-PCR, all ABC transporters known to date in humans were examined in tissue samples from human cornea, conjunctiva, meibomian glands and lacrimal glands. The RT-PCR analyses revealed the presence of all ABC transporters in the samples examined, although the results for some of the 48 transporters known in human and analyzed were different in the various tissues. The present results provide information on the expression of ABC transporters at the mRNA level on the ocular surface and in the lacrimal system. Their detection forms the basis for follow-up studies at the protein level, which will provide more information about their physiological significance at the ocular surface and in the lacrimal system and which may explain pathological effects such as drug resistance.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Túnica Conjuntiva , Córnea , Aparelho Lacrimal , Humanos , Aparelho Lacrimal/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Córnea/metabolismo , Túnica Conjuntiva/metabolismo , Glândulas Tarsais/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Ann Anat ; 255: 152274, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38740350

RESUMO

BACKGROUND: To investigate the geometric morphological differences of the lacrimal punctum by analyzing its shape in relation to age and sex in a normal population. METHODS: 960 high-magnification slit-lamp images were obtained from 320 puncta of normal asymptomatic Indian individuals across eight decades of life. Using advanced geometric morphometric techniques, including Elliptic Fourier Analysis and Principal Component Analysis, the intricate details of the lacrimal punctum's shape in a diverse population sample were categorized by age and sex. High-resolution images of the lacrimal punctum underwent standardization for scale and orientation, followed by precise landmark identification and coordinate data extraction. RESULTS: The geometric morphometry of the lacrimal punctum shows significant changes as one ages. However, the gender differences, in isolation, without consideration of age, remain subtle and are not pronounced. Interestingly, detailed Principal Component scores analysis revealed potential sex- and age-related variations specifically for the left and right lower puncta, which warrant further investigation. These changes could reflect unique aging changes in the proximal lacrimal drainage system. CONCLUSION: The study is a starting point for geometric morphometric analysis of the lacrimal punctum and provides valuable insights into the punctal changes in size, orientation, and overall morphology across different age groups and between sexes. These findings highlight the significance of considering individual age-wise anatomical variations to better understand the lacrimal punctum.


Assuntos
Aparelho Lacrimal , Análise de Componente Principal , Humanos , Masculino , Feminino , Adulto , Aparelho Lacrimal/anatomia & histologia , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , Envelhecimento , Caracteres Sexuais , Criança , Valores de Referência
20.
Int Ophthalmol ; 44(1): 213, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700596

RESUMO

PURPOSE: This study aimed to explore the diagnostic value of whole-orbit-based multiparametric assessment on Dixon MRI for the evaluation of the thyroid eye disease (TED) activity. METHODS: The retrospective study enrolled patients diagnosed as TED and obtained their axial and coronal Dixon MRI scans. Multiparameters were assessed, including water fraction (WF), fat fraction (FF) of extraocular muscles (EOMs), orbital fat (OF), and lacrimal gland (LG). The thickness of OF and herniation of LG were also measured. Univariable and multivariable logistic regression was applied to construct prediction models based on single or multiple structures. Receiver operating characteristic (ROC) curve analysis was also implemented. RESULTS: Univariable logistic analysis revealed significant differences in water fraction (WF) of the superior rectus (P = 0.018), fat fraction (FF) of the medial rectus (P = 0.029), WF of OF (P = 0.004), and herniation of LG (P = 0.012) between the active and inactive TED phases. Multivariable logistic analysis and corresponding receiver operating characteristic curve (ROC) analysis of each structure attained the area under the curve (AUC) values of 0.774, 0.771, and 0.729 for EOMs, OF, and LG, respectively, while the combination of the four imaging parameters generated a final AUC of 0.909. CONCLUSIONS: Dixon MRI may be used for fine multiparametric assessment of multiple orbital structures. The whole-orbit-based model improves the diagnostic performance of TED activity evaluation.


Assuntos
Oftalmopatia de Graves , Músculos Oculomotores , Órbita , Curva ROC , Humanos , Masculino , Feminino , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/diagnóstico por imagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Órbita/diagnóstico por imagem , Órbita/patologia , Músculos Oculomotores/diagnóstico por imagem , Músculos Oculomotores/patologia , Adulto , Idoso , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Imageamento por Ressonância Magnética/métodos , Aparelho Lacrimal/diagnóstico por imagem , Aparelho Lacrimal/patologia
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