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1.
Int J Nanomedicine ; 19: 4045-4060, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736656

RESUMEN

Purpose: Dry eye disease (DED) is a multifactorial ocular surface disease with a rising incidence. Therefore, it is urgent to construct a reliable and efficient drug delivery system for DED treatment. Methods: In this work, we loaded C-dots nanozyme into a thermosensitive in situ gel to create C-dots@Gel, presenting a promising composite ocular drug delivery system to manage DED. Results: This composite ocular drug delivery system (C-dots@Gel) demonstrated the ability to enhance adherence to the corneal surface and extend the ocular surface retention time, thereby enhancing bioavailability. Furthermore, no discernible ocular surface irritation or systemic toxicity was observed. In the DED mouse model induced by benzalkonium chloride (BAC), it was verified that C-dots@Gel effectively mitigated DED by stabilizing the tear film, prolonging tear secretion, repairing corneal surface damage, and augmenting the population of conjunctival goblet cells. Conclusion: Compared to conventional dosage forms (C-dots), the C-dots@Gel could prolong exhibited enhanced retention time on the ocular surface and increased bioavailability, resulting in a satisfactory therapeutic outcome for DED.


Asunto(s)
Antioxidantes , Carbono , Córnea , Síndromes de Ojo Seco , Hidrogeles , Animales , Síndromes de Ojo Seco/tratamiento farmacológico , Ratones , Carbono/química , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacología , Antioxidantes/administración & dosificación , Hidrogeles/química , Hidrogeles/administración & dosificación , Hidrogeles/farmacocinética , Córnea/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Modelos Animales de Enfermedad , Disponibilidad Biológica , Lágrimas/efectos de los fármacos , Lágrimas/química , Compuestos de Benzalconio/química , Compuestos de Benzalconio/administración & dosificación , Compuestos de Benzalconio/farmacocinética , Femenino , Masculino , Temperatura , Puntos Cuánticos/química
2.
J Nanobiotechnology ; 22(1): 229, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720321

RESUMEN

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.


Asunto(s)
Síndromes de Ojo Seco , Soluciones Oftálmicas , Especies Reactivas de Oxígeno , Soluciones Oftálmicas/química , Soluciones Oftálmicas/farmacología , Síndromes de Ojo Seco/tratamiento farmacológico , Animales , Especies Reactivas de Oxígeno/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Córnea/efectos de los fármacos , Córnea/metabolismo , Alcohol Polivinílico/química , Humanos , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Boratos/química , Nanopartículas/química , Masculino
3.
Transl Vis Sci Technol ; 13(5): 13, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38767906

RESUMEN

Purpose: The purpose of this study was to conduct a large-scale genome-wide association study (GWAS) and construct a polygenic risk score (PRS) for risk stratification in patients with dry eye disease (DED) using the Taiwan Biobank (TWB) databases. Methods: This retrospective case-control study involved 40,112 subjects of Han Chinese ancestry, sourced from the publicly available TWB. Cases were patients with DED (n = 14,185), and controls were individuals without DED (n = 25,927). The patients with DED were further divided into 8072 young (<60 years old) and 6113 old participants (≥60 years old). Using PLINK (version 1.9) software, quality control was carried out, followed by logistic regression analysis with adjustments for sex, age, body mass index, depression, and manic episodes as covariates. We also built PRS prediction models using the standard clumping and thresholding method and evaluated their performance (area under the curve [AUC]) through five-fold cross-validation. Results: Eleven independent risk loci were identified for these patients with DED at the genome-wide significance levels, including DNAJB6, MAML3, LINC02267, DCHS1, SIRPB3P, HULC, MUC16, GAS2L3, and ZFPM2. Among these, MUC16 encodes mucin family protein. The PRS model incorporated 932 and 740 genetic loci for young and old populations, respectively. A higher PRS score indicated a greater DED risk, with the top 5% of PRS individuals having a 10-fold higher risk. After integrating these covariates into the PRS model, the area under the receiver operating curve (AUROC) increased from 0.509 and 0.537 to 0.600 and 0.648 for young and old populations, respectively, demonstrating the genetic-environmental interaction. Conclusions: Our study prompts potential candidates for the mechanism of DED and paves the way for more personalized medication in the future. Translational Relevance: Our study identified genes related to DED and constructed a PRS model to improve DED prediction.


Asunto(s)
Síndromes de Ojo Seco , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Herencia Multifactorial , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Síndromes de Ojo Seco/genética , Síndromes de Ojo Seco/epidemiología , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/genética , Adulto , Herencia Multifactorial/genética , Anciano , Factores de Riesgo , Medición de Riesgo/métodos , Polimorfismo de Nucleótido Simple , Taiwán/epidemiología , Puntuación de Riesgo Genético
4.
BMJ Open Ophthalmol ; 9(1)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702178

RESUMEN

BACKGROUND: Dry eye disease is the most commonplace multifractional ocular complication, which has already affected millions of people in the world. It is identified by the excessive buildup of reactive oxygen species, leading to substantial corneal epithelial cell demise and ocular surface inflammation attributed to TLR4. In this study, we aimed to identify potential compounds to treat of dry eye syndrome by exploring in silico methods. METHODS: In this research, molecular docking and dynamics simulation tests were used to examine the effects of selected compounds on TLR4 receptor. Compounds were extracted from different databases and were prepared and docked against TLR4 receptor via Autodock Vina. Celastrol, lumacaftor and nilotinib were selected for further molecular dynamics studies for a deeper understanding of molecular systems consisting of protein and ligands by using the Desmond module of the Schrodinger Suite. RESULTS: The docking results revealed that the compounds are having binding affinity in the range of -5.1 to -8.78 based on the binding affinity and three-dimensional interactions celastrol, lumacaftor and nilotinib were further studied for their activity by molecular dynamics. Among the three compounds, celastrol was the most stable based on molecular dynamics trajectory analysis from 100 ns in the catalytic pockets of 2Z63.pdb.pdb. Root mean square deviation of celastrol/2Z63 was in the range of 1.8-4.8 Å. CONCLUSION: In particular, Glu376 of TLR4 receptor is crucial for the identification and binding of lipopolysaccharides (LPS), which are part of Gram-negative bacteria's outer membrane. In our investigation, celastrol binds to Glu376, suggesting that celastrol may prevent the dry eye syndrome by inhibiting LPS's binding to TLR4.


Asunto(s)
Síndromes de Ojo Seco , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Triterpenos Pentacíclicos , Pirimidinas , Receptor Toll-Like 4 , Síndromes de Ojo Seco/tratamiento farmacológico , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/química , Humanos , Triterpenos Pentacíclicos/farmacología , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/uso terapéutico , Pirimidinas/farmacología , Pirimidinas/química , Pirimidinas/uso terapéutico , Triterpenos/farmacología , Triterpenos/química , Simulación por Computador , Ligandos , Aminopiridinas/farmacología , Aminopiridinas/química , Aminopiridinas/uso terapéutico
5.
J Nanobiotechnology ; 22(1): 233, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38725011

RESUMEN

BACKGROUND: Dry Eye Disease (DED) is a prevalent multifactorial ocular disease characterized by a vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the ocular surface, all of which lead to DED deterioration and impair the patients' quality of life and social functioning. Currently, anti-inflammatory drugs have shown promising efficacy in treating DED; however, such drugs are associated with side effects. The bioavailability of ocular drugs is less than 5% owing to factors such as rapid tear turnover and the presence of the corneal barrier. This calls for investigations to overcome these challenges associated with ocular drug administration. RESULTS: A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study. In terms of delivery, PHP-DPS@INS nanoparticles (NPs) overcame the ocular surface transport barrier by adopting the strategy of "ocular surface electrostatic adhesion-lysosomal site-directed escape". In terms of therapy, PHP-DPS@INS achieved mitochondrial targeting and antioxidant effects through SS-31 peptide, and exerted an anti-inflammatory effect by loading insulin to reduce mitochondrial inflammatory metabolites. Ultimately, the synergistic action of "anti-inflammation-antioxidation-mitochondrial function restoration" breaks the vicious cycle associated with DED. The PHP-DPS@INS demonstrated remarkable cellular uptake, lysosomal escape, and mitochondrial targeting in vitro. Targeted metabolomics analysis revealed that PHP-DPS@INS effectively normalized the elevated level of mitochondrial proinflammatory metabolite fumarate in an in vitro hypertonic model of DED, thereby reducing the levels of key inflammatory factors (IL-1ß, IL-6, and TNF-α). Additionally, PHP-DPS@INS strongly inhibited reactive oxygen species (ROS) production and facilitated mitochondrial structural repair. In vivo, the PHP-DPS@INS treatment significantly enhanced the adhesion duration and corneal permeability of the ocular surface in DED mice, thereby improving insulin bioavailability. It also restored tear secretion, suppressed ocular surface damage, and reduced inflammation in DED mice. Moreover, it demonstrated favorable safety profiles both in vitro and in vivo. CONCLUSION: In summary, this study successfully developed a comprehensive DED management nanosystem that overcame the ocular surface transmission barrier and disrupted the vicious cycle that lead to dry eye pathogenesis. Additionally, it pioneered the regulation of mitochondrial metabolites as an anti-inflammatory treatment for ocular conditions, presenting a safe, efficient, and innovative therapeutic strategy for DED and other inflammatory diseases.


Asunto(s)
Síndromes de Ojo Seco , Inflamación , Liposomas , Mitocondrias , Estrés Oxidativo , Síndromes de Ojo Seco/tratamiento farmacológico , Animales , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Liposomas/química , Inflamación/tratamiento farmacológico , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/química , Nanopartículas/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Córnea/metabolismo , Córnea/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Oligopéptidos
6.
Vestn Oftalmol ; 140(2): 102-111, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-38742506

RESUMEN

Dry eye disease (DED) is pathogenetically based on inflammation of the ocular surface. A step-by-step approach to DED treatment involves early initiation of anti-inflammatory therapy, including instillation of cyclosporine A (CsA). However, recommendations for the use of topical CsA in clinical practice are limited. This article presents an expert consensus on practical recommendations for the management of patients with DED, including indications, time of initiation and duration of CsA therapy, comparison of CsA forms currently registered in the Russian Federation, as well as issues of patient education.


Asunto(s)
Ciclosporina , Emulsiones , Humanos , Administración Oftálmica , Ciclosporina/administración & dosificación , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/etiología , Inmunosupresores/administración & dosificación , Soluciones Oftálmicas/administración & dosificación , Resultado del Tratamiento , Xeroftalmia/etiología , Xeroftalmia/tratamiento farmacológico , Xeroftalmia/diagnóstico
7.
Int Ophthalmol ; 44(1): 211, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696090

RESUMEN

PURPOSE: To evaluate the effects of sodium hyaluronate drops on dry eye parameters and corneal epithelial thickness following cataract surgery. METHODS: The study included 84 patients who underwent uncomplicated phacoemulsification. In Group A, 0.15% sodium hyaluronate drops were added to the postoperative antibiotic/anti-inflammatory treatment. In Group B, only antibiotic/anti-inflammatory treatment was applied. Preoperatively and at 1 week and 1 month postoperatively, all the patients were evaluated in respect of tear break-up time (TBUT), the Schirmer test under anesthesia, the corneal fluorescein staining (CFS) score, mean central corneal thickness (CCT) and mean central corneal epithelial thickness (CCET), and the two groups were compared. RESULTS: A statistically significant difference was determined between the two groups at postoperative 1 month in respect of TBUT, Schirmer test, CFS score, and CCET (p < 0.01). In Group A, a statistically significant increase was determined in the TBUT and Schirmer values at 1 month postoperatively (p < 0.01, p = 0.01, respectively) and in Group B, these values were decreased compared to preoperatively (p < 0.01). The CCET was determined to be significantly thinner in Group B 1 month postoperatively (p < 0.01). A significant increase in CCT was observed in both groups at postoperative 1 week (p < 0.01) and preoperative values were reached at 1 month postoperatively. CONCLUSION: In the patient group using sodium hyaluronate, significant differences were determined in all dry eye parameters and CCET. The use of hyaluronate sodium drops after cataract surgery was seen to improve dry eye parameters and contribute to a healthy ocular surface by ensuring continuity of the corneal epithelium.


Asunto(s)
Síndromes de Ojo Seco , Epitelio Corneal , Ácido Hialurónico , Soluciones Oftálmicas , Facoemulsificación , Humanos , Ácido Hialurónico/administración & dosificación , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/diagnóstico , Femenino , Masculino , Anciano , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/patología , Persona de Mediana Edad , Soluciones Oftálmicas/administración & dosificación , Facoemulsificación/métodos , Viscosuplementos/administración & dosificación , Estudios Prospectivos , Lágrimas/metabolismo , Complicaciones Posoperatorias/prevención & control , Extracción de Catarata/métodos
8.
Int Ophthalmol ; 44(1): 215, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38705919

RESUMEN

PURPOSE: There is limited literature on the ocular manifestations in patients with psoriasis. Therefore, this study aimed to identify the prevalence of and factors associated with ocular manifestations in adults with psoriasis. METHODS: This cross-sectional study included Brazilian adults with psoriasis. The dermatological evaluation included diagnosis, clinical form, Psoriasis Area and Severity Index (PASI) measurement, and location of the lesions. Patients underwent a full ophthalmological examination, including the Schirmer I test, Rose Bengala staining, and tear breakup time tests. The results were analyzed using chi-square and Pearson's linear correlation tests. RESULTS: Of the 130 patients assessed, 118 (90.8%) exhibited ocular abnormalities, with meibomian gland dysfunction (MGD) being the most prevalent (59.2%), followed by dry eye disease (DED) (56.2%). A significant correlation was observed between MGD and PASI (p = 0.05), and between MGD and certain treatment modalities. DED was significantly associated with PASI (p < 0.05). Concurrent use of acitretin was identified as an independent predictor of MGD (odds ratio [OR] = 3.5, p < 0.05), whereas PASI was a protective factor against DED (OR = 0.39, p < 0.01). CONCLUSION: Given the high prevalence of eye disease among individuals with psoriasis, routine ophthalmological assessments are recommended to prevent possible ocular complications.


Asunto(s)
Síndromes de Ojo Seco , Psoriasis , Humanos , Estudios Transversales , Masculino , Psoriasis/epidemiología , Psoriasis/complicaciones , Femenino , Brasil/epidemiología , Adulto , Persona de Mediana Edad , Prevalencia , Síndromes de Ojo Seco/epidemiología , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/diagnóstico , Disfunción de la Glándula de Meibomio/epidemiología , Disfunción de la Glándula de Meibomio/diagnóstico , Disfunción de la Glándula de Meibomio/etiología , Índice de Severidad de la Enfermedad , Anciano , Adulto Joven
9.
Exp Biol Med (Maywood) ; 249: 10175, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756167

RESUMEN

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.


Asunto(s)
Acuaporina 5 , Diabetes Mellitus Experimental , Aparato Lagrimal , Naltrexona , Ratas Sprague-Dawley , Lágrimas , Animales , Aparato Lagrimal/metabolismo , Aparato Lagrimal/efectos de los fármacos , Aparato Lagrimal/patología , Lágrimas/metabolismo , Lágrimas/efectos de los fármacos , Naltrexona/farmacología , Masculino , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Ratas , Acuaporina 5/metabolismo , Administración Tópica , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/patología , Síndromes de Ojo Seco/metabolismo
10.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38731998

RESUMEN

Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern.


Asunto(s)
Síndromes de Ojo Seco , Lipidómica , Lípidos , Disfunción de la Glándula de Meibomio , Glándulas Tarsales , Lágrimas , Humanos , Lipidómica/métodos , Glándulas Tarsales/metabolismo , Síndromes de Ojo Seco/metabolismo , Lágrimas/metabolismo , Lágrimas/química , Lípidos/análisis , Femenino , Masculino , Persona de Mediana Edad , Disfunción de la Glándula de Meibomio/metabolismo , Adulto , Anciano , Metabolismo de los Lípidos
12.
Cells ; 13(7)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38607061

RESUMEN

The lacrimal gland is crucial for maintaining ocular health by producing the aqueous component of the tear film, which hydrates and nourishes the ocular surface. Decreased production of this component results in dry eye disease, a condition affecting over 250 million people worldwide. However, the scarcity of primary human material for studying its underlying mechanisms and the absence of a cell model for human lacrimal gland epithelial cells present significant challenges. Here, we describe the generation of immortalized human lacrimal gland cell lines through the introduction of an SV40 antigen. We successfully isolated and characterized three cell clones from a female lacrimal gland donor, confirming their epithelial identity through genomic and protein analyses, including PCR, RNAseq, immunofluorescence and cultivation in a 3D spheroid model. Our findings represent a significant advancement, providing improved accessibility to investigate the molecular pathogenesis mechanisms of dry eye disease and potential therapeutic interventions. We identified the expression of typical epithelial cell marker genes and demonstrated the cells' capability to form 2D cell sheets and 3D spheroids. This establishment of immortalized human lacrimal gland cells with epithelial characteristics holds promise for future comprehensive studies, contributing to a deeper understanding of dry eye disease and its cellular mechanisms.


Asunto(s)
Síndromes de Ojo Seco , Aparato Lagrimal , Humanos , Femenino , Aparato Lagrimal/metabolismo , Lágrimas/metabolismo , Síndromes de Ojo Seco/metabolismo , Línea Celular
13.
Int Ophthalmol ; 44(1): 177, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622271

RESUMEN

PURPOSE: This review examined existing literature to determine various ocular manifestations of liver pathologies, with a focus on metabolic deficiencies as well as viral and immune liver conditions. METHODS: Recent data were compiled from PubMed from 2000 to 2020 using keywords that were relevant to the assessed pathologies. Ocular presentations of several liver pathologies were researched and then summarized in a comprehensive form. RESULTS: Several ocular manifestations of liver disease were related to vitamin A deficiency, as liver disease is associated with impaired vitamin A homeostasis. Alcoholic liver cirrhosis can result in vitamin A deficiency, presenting with Bitot spots, xerosis, and corneal necrosis. Congenital liver diseases such as mucopolysaccharidoses and peroxisomal disorders are also linked with ocular signs. Viral causes of liver disease have associations with conditions like retinal vasculitis, keratoconjunctivitis sicca, retinopathies, Mooren's ulcer, and Sjogren's syndrome. Autoimmune hepatitis has been linked to peripheral ulcerative keratitis and uveitis. CONCLUSIONS: Building strong associations between ocular and liver pathology will allow for early detection of such conditions, leading to the early implementation of management strategies. While this review outlines several of the existing connections between hepatic and ophthalmic disease, further research is needed in the area in order to strengthen these associations.


Asunto(s)
Úlcera de la Córnea , Síndromes de Ojo Seco , Queratoconjuntivitis Seca , Hepatopatías , Vasculitis Retiniana , Síndrome de Sjögren , Deficiencia de Vitamina A , Humanos , Deficiencia de Vitamina A/complicaciones , Queratoconjuntivitis Seca/etiología , Úlcera de la Córnea/diagnóstico , Síndrome de Sjögren/complicaciones , Síndromes de Ojo Seco/complicaciones , Hepatopatías/etiología , Hepatopatías/complicaciones , Vasculitis Retiniana/complicaciones
14.
Int Ophthalmol ; 44(1): 190, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38652333

RESUMEN

PURPOSE: Somatization is an important mental process that may causes medically unexplained and treatment-resistant somatic symptoms. The aim of the study is assess the presence of somatization in patients with dry eye disease (DED). METHODS: Eighty-eight patients with no objective DED finding and ongoing DED treatment were included in this prospective and observational study. Patients with subjective symptoms formed the symptom group and patients without subjective symptoms formed the control group. All patients were scored with the Turkish version of the Ocular Surface Disease Index (OSDI), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Symptom Checklist-90-R (SCL-90R) somatization subscale, Toronto Alexithymia Scale (TAS), Pain Catastrophizing Scale (PCS), and Symptom Interpretation Questionnaire (SIQ). RESULTS: Mean OSDI score was significantly higher in the symptom group than in the control group. The mean HAM-D and HAM-A outcomes did not differ between the groups. The mean SCL-90R somatization subscale, TAS, and PCS scores were significantly higher in the symptom group than in the control group. In the SIQ, somatic attributional style score was significantly higher in the symptom group than in the control group. The SCL-90R somatization subscale, PCS, and somatic attributional style scores had positive and mild-moderate correlation with OSDI scores in the symptom group. The TAS score had positive and moderate correlation with OSDI scores in all sample analyses. CONCLUSION: Somatization should be considered in patients with DED with chronic ocular surface symptoms. Presence of subjective symptoms resistant to treatment may be an indicator of somatization.


Asunto(s)
Síndromes de Ojo Seco , Trastornos Somatomorfos , Humanos , Síndromes de Ojo Seco/psicología , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/etiología , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Trastornos Somatomorfos/psicología , Trastornos Somatomorfos/diagnóstico , Adulto , Encuestas y Cuestionarios , Anciano
15.
BMC Ophthalmol ; 24(1): 152, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38581010

RESUMEN

OBJECTIVE: The purpose of this article is to systematically review the association between dry eye and sleep quality. METHODS: PubMed, EMBASE, Cochrane, Web of Science, and grey literature databases were searched for observational studies published before April 2023. Meta-analysis was performed using STAT15 software. RESULTS: A total of 21 studies with 419,218 participants were included. The results showed that the dry eye subjects had a worse sleep quality than the healthy population, with poorer subjective sleep quality, longer sleep latency, and a higher risk of unhealthy sleep duration such as insufficient sleep or excessive sleep. The Pittsburgh Sleep Quality Index (PSQI) scores of the dry eye subjects were significantly higher than those of the control subjects (WMD = 1.78, 95%CI: 1.06, 2.50, P < 0.001). The dry eye subjects scored higher than the control subjects in sleep quality, sleep latency, and sleep disturbance in PSQI; there was no difference between the dry eye individuals and control subjects in sleep duration, sleep efficiency, daytime dysfunction, and sleep medication scores. The risk of sleep disorders in the dry eye subjects was significantly higher than that in the non-dry eye subjects (RR = 2.20, 95%CI: 1.78, 2.72, P < 0.001); the risk of insufficient sleep in the dry eye subjects was higher than that in the control subjects (RR = 3.76, 95%CI: 3.15, 4.48, P < 0.001), and the prevalence of excessive sleepiness in dry eye subjects was higher than that in the control subjects (RR = 5.53, 95%CI: 3.83, 7.18, P < 0.001). The ESS scores of the dry eye subjects were significantly higher than those of the control subjects (WMD = 3.02, 95%CI: 2.43, 3.60, P < 0.01). CONCLUSION: Our meta-analysis suggests that individuals with dry eye have a worse sleep quality than the healthy population, with poorer subjective sleep quality, longer sleep latency, and higher risk of unhealthy sleep duration such as insufficient sleep or excessive sleepiness.


Asunto(s)
Síndromes de Ojo Seco , Trastornos del Sueño-Vigilia , Humanos , Calidad del Sueño , Privación de Sueño , Somnolencia , Síndromes de Ojo Seco/epidemiología , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/epidemiología , Sueño
16.
Invest Ophthalmol Vis Sci ; 65(4): 33, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38648040

RESUMEN

Purpose: The cGAS-STING pathway has been shown to be an important mediator of inflammation. There is emerging evidence of the importance of this signaling cascade in a variety of inflammatory diseases settings. Here, we present evidence that the mitochondrial DNA (mtDNA) damage-mediated cGAS-STING pathway plays an important role in the induction of inflammation in environmental dry eye (DE). Methods: RT-qPCR and Western blot were used to assess the induction of the cGAS-STING pathway and inflammatory cytokines in environmental DE mouse model, primary human corneal epithelial cells (pHCECs), and patients with DE. RNA sequencing was used to determine mRNA expression patterns of high osmotic pressure (HOP)-stimulated pHCECs. mtDNA was detected with electron microscopy, flow cytometry, and immunofluorescent staining. mtDNA was isolated and transfected into pHCECs for evaluating the activation of the cGAS-STING pathway. Results: The expression levels of cGAS, STING, TBK1, IRF3, and IFNß were significantly increased in an environmental DE model and HOP-stimulated pHCECs. The STING inhibitor decreased the expression of inflammatory factors in DE. An upregulation of STING-mediated immune responses and IRF3 expression mediated by TBK1 were observed in the HOP group. HOP stimulation induced mitochondrial oxidative damage and the leakage of mtDNA into the cytoplasm. Then, mtDNA activated the cGAS-STING pathway and induced intracytoplasmic STING translocated to the Golgi apparatus. Finally, we also found activated cGAS-STING signaling in the human conjunctival blot cell of patients with DE. Conclusions: Our findings suggest that the cGAS-STING pathway is activated by recognizing cytoplasmic mtDNA leading to STING translocation, further exacerbating the development of inflammation in environmental DE.


Asunto(s)
ADN Mitocondrial , Síndromes de Ojo Seco , Proteínas de la Membrana , Nucleotidiltransferasas , Transducción de Señal , Animales , Femenino , Humanos , Ratones , Western Blotting , Células Cultivadas , Modelos Animales de Enfermedad , ADN Mitocondrial/metabolismo , ADN Mitocondrial/fisiología , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/metabolismo , Epitelio Corneal/metabolismo , Citometría de Flujo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones Endogámicos C57BL , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/fisiología
17.
Front Cell Infect Microbiol ; 14: 1340075, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38628549

RESUMEN

Purpose: To determine the effects of EV-A71 (Enterovirus A71) infection on ocular surface and its mechanism. Methods: AG6 mice aged two to three weeks were randomly divided into control and EV-A71 infected groups. Slit-lamp observation, fluorescein staining, and phenol red thread test were used to assess symptoms of ocular surface at 4 dpi (days post infection). The pathological changes of cornea and lacrimal gland were observed by H&E staining, PAS staining, TUNEL assay, IHC staining and qRT-PCR. Corneas and lacrimal glands from mice were obtained and processed for RNA sequencing analysis. Newly diagnosed HFMD patients caused by EV-A71 were recruited and ensured they met the inclusion criteria. Ocular surface parameters (TMH and NIKBUT) were measured using the OCULUS Keratograph 5M. Tear samples were taken to examine Cxcl1 and IL-6 levels through the ELISA method. Results: Mice studies revealed that EV-A71 infection caused tear film instability, decreased tear secretions, decreased in lacrimal gland size, and distinct goblet cell loss. It also resulted in increased large vacuoles within acinar cells and structural damage in lacrimal gland. Apart from minor damage to the epidermis, there was no obvious inflammatory changes or apoptosis in the cornea. However, there were significant inflammatory injury and apoptosis in the lacrimal gland. RNA-seq analysis showed IL-17 and NF-κB signaling pathways were activated in the lacrimal glands of mice infected with EV-A71. In HFMD patients, the THM was in a low range and NITBUT was significantly shorter than the control group by Oculus Keratograph 5M. ELISA assay showed a higher tear Cxcl1 and IL-6 level in them. Conclusion: EV-A71 infection affected lacrimal gland structure and function and induced dry eye-like symptoms.


Asunto(s)
Síndromes de Ojo Seco , Enterovirus Humano A , Infecciones por Enterovirus , Enterovirus , Aparato Lagrimal , Humanos , Animales , Ratones , Interleucina-6 , Síndromes de Ojo Seco/etiología
18.
Lasers Med Sci ; 39(1): 111, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656565

RESUMEN

Intense pulsed light (IPL) is a non-laser, high-intensity light source that has been shown to play a valuable role in dermatology and has been adopted in ophthalmology for treating meibomian gland dysfunction (MGD). In this review, we discuss the mechanism of action of IPL, including its benefits in ophthalmology. IPL therapy has been shown to improve tear film stability, meibomian gland (MG) function, and subjective symptoms of ocular dryness in MGD patients. Moreover, emerging evidence suggests that IPL therapy is beneficial for other ocular surface diseases, such as blepharitis and chalazia. Hence, it can be inferred that IPL has potential as a therapeutic modality in future applications. Large clinical and experimental trials are needed to exploit the full potential of IPL as a treatment for recurrent chalazia, Sjögren's syndrome, and other causes of dry eye disease (DED). This paper reviews the published literature related to the application of IPL for treating ocular surface diseases.


Asunto(s)
Síndromes de Ojo Seco , Tratamiento de Luz Pulsada Intensa , Disfunción de la Glándula de Meibomio , Humanos , Tratamiento de Luz Pulsada Intensa/métodos , Síndromes de Ojo Seco/terapia , Disfunción de la Glándula de Meibomio/terapia , Blefaritis/terapia , Glándulas Tarsales
20.
J Refract Surg ; 40(4): e229-e238, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38593259

RESUMEN

PURPOSE: To evaluate the effects of topical 0.05% cyclosporine A on Ocular Surface Disease Index (OSDI) score and ocular surface parameters after small incision lenticule extraction (SMILE) for myopia. METHODS: In this study, 151 patients who underwent SMILE were randomized into the control group (71 eyes) and the 0.05% cyclosporine A group (80 eyes). Both groups received standard treatment during the 1 month after SMILE. Over the next 3 months, The control group continued standard therapy (0.3% sodium hyaluronate) and the 0.05% cyclosporine A group received additional 0.05% cyclosporine A. OSDI total and subscale scores, non-invasive tear break-up time (NIBUT), tear lipid layer thickness (LLT), and tear meniscus height (TMH) were assessed preoperatively and postoperatively. RESULTS: Compared to baseline, the OSDI scores significantly increased in both groups (P < .001). The 0.05% cyclosporine A group exhibited lower OSDI total scores after administering 0.05% cyclosporine A versus the control group (P = .026). At 1 month of follow-up, NIBUT, LLT, and TMH values significantly decreased in both groups compared to baseline (P < .05). The 0.05% cyclosporine A group exhibited higher NIBUT, LLT, and TMH versus the control group, returning to preoperative values after 2 months. Overall, the OSDI total score and NIBUT values during follow-up were not significantly different between the two groups; however, the LLT and TMH values were significantly different between the two groups (P < .001 and .041, respectively) by repeated measures analysis of variance. CONCLUSIONS: Topical 0.05% cyclosporine A was effective in relieving subjective dry eye symptoms and maintaining ocular surface stability in the early postoperative period of SMILE. [J Refract Surg. 2024;40(4):e229-e238.].


Asunto(s)
Síndromes de Ojo Seco , Queratomileusis por Láser In Situ , Miopía , Humanos , Ciclosporina/uso terapéutico , Miopía/cirugía , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/etiología , Lágrimas
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