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1.
Exp Eye Res ; 240: 109814, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38307190

RESUMEN

Neurotrophic keratopathy (NK) is a challenging disease with the reduced innervation to the cornea. To establish a genetic and stable mouse model of NK, we utilized the TRPV1-DTR mice with intraperitoneal injection of diphtheria toxin (DT) to selectively eliminate TRPV1 neurons. After DT administration, the mice exhibited robust ablation of TRPV1 neurons in the trigeminal ganglion, accompanied with reduced corneal sensation and nerve density, as well as the decreased calcitonin-gene-related peptide (CGRP) and substance P levels. According to disease progression of TRPV1 neuronal ablation, tear secretion was reduced from day 3, which followed by corneal epithelial punctate lesions from day 7. From day 11 to day 16, the mice exhibited persistent corneal epithelial defects and stromal edema. By day 21, corneal ulceration and stromal melting were observed with the abundant inflammatory cell infiltration, corneal neovascularization, and enhanced cell apoptosis. Moreover, subconjunctival injection of CGRP delayed the NK progression with the characteristics of reduced severe corneal epithelial lesions and corneal inflammation. In addition, the impairments of conjunctival goblet cells, lacrimal gland, and meibomian gland were identified by the diminished expression of MUC5AC, AQP5, and PPARγ, respectively. Therefore, these results suggest that the TRPV1-DTR mice may serve as a reliable animal model for the research of NK pathogenesis.


Asunto(s)
Distrofias Hereditarias de la Córnea , Queratitis , Enfermedades del Nervio Trigémino , Ratones , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Córnea/metabolismo , Neuronas/metabolismo , Modelos Animales de Enfermedad , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo
2.
Mol Biol Rep ; 51(1): 755, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874707

RESUMEN

BACKGROUND: Cataract contributes to visual impairment worldwide, and diabetes mellitus accelerates the formation and progression of cataract. Here we found that the expression level of miR-204-5p was diminished in the lens epithelium with anterior lens capsule of cataract patients compared to normal donors, and decreased more obviously in those of diabetic cataract (DC) patients. However, the contribution and mechanism of miR-204-5p during DC development remain elusive. METHODS AND RESULT: The mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model. CONCLUSIONS: Our results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC.


Asunto(s)
Catarata , Complicaciones de la Diabetes , Células Epiteliales , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina , MicroARNs , Mitocondrias , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Catarata/genética , Catarata/metabolismo , Catarata/patología , Mitocondrias/metabolismo , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Células Epiteliales/metabolismo , Complicaciones de la Diabetes/genética , Complicaciones de la Diabetes/metabolismo , Potencial de la Membrana Mitocondrial , Cristalino/metabolismo , Cristalino/patología , Masculino , Femenino , Persona de Mediana Edad
3.
Invest Ophthalmol Vis Sci ; 65(11): 36, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39312222

RESUMEN

Purpose: The purpose of this study was to investigate whether corneal lesions in mice with type 2 diabetes mellitus (T2D) infected with herpes simplex virus (HSV)-1 are more severe, and to elucidate the specific underlying mechanism. Methods: The corneas of control mice and T2D mice induced by a high-fat diet combined with streptozotocin were infected with the HSV-1 Mckrae strain to assess corneal infection, opacity, and HSV-1 replication. RNA sequencing of the corneal epithelium from wild-type and db/db mice (a genetic T2D mouse model) was conducted to identify the key gene affecting T2D infection. Immunofluorescence staining was performed on corneal sections from T2D mice and patients with T2D. The effect of small interfering RNA (siRNA) knockdown on corneal HSV-1 infection was evaluated in both in vitro and in vivo models. Results: T2D mice exhibited a more severe infection phenotype following HSV-1 infection, characterized by augmented corneal opacity scores, elevated viral titers, and transcripts compared to control mice. Transcriptome analysis of corneal epithelium revealed a hyperactive viral response in T2D mice, highlighting the differentially expressed gene Rtp4 (encoding receptor transporter protein 4). Receptor transporter protein 4 (RTP4) expression was enhanced in the corneal epithelium of T2D mice and patients with T2D. Virus binding assays demonstrated that RTP4 facilitated HSV-1 binding to human corneal epithelial cells. Silencing RTP4 alleviated HSV-1 infection in both in vitro and in vivo T2D models. Conclusions: The findings indicate that elevated RTP4 exacerbates HSV-1 infection by enhancing its binding to corneal epithelial cells, whereas Rtp4 knockdown mitigated corneal lesions in T2D mice. This implies RTP4 as a potential target for intervention in diabetic HSV-1 infection.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Epitelio Corneal , Herpesvirus Humano 1 , Queratitis Herpética , Ratones Endogámicos C57BL , Animales , Herpesvirus Humano 1/fisiología , Herpesvirus Humano 1/genética , Ratones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/genética , Queratitis Herpética/virología , Queratitis Herpética/metabolismo , Queratitis Herpética/patología , Diabetes Mellitus Experimental/virología , Epitelio Corneal/virología , Epitelio Corneal/metabolismo , Epitelio Corneal/patología , Humanos , Replicación Viral/fisiología , Proteínas de Transporte de Membrana/genética , Masculino , Modelos Animales de Enfermedad
4.
Adv Ophthalmol Pract Res ; 3(3): 134-140, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37846363

RESUMEN

Background: To report the clinical consequences and laboratory characteristics of late postoperative opacification of a hydrophilic acrylic intraocular lens (US-860UV IOL) as well as the prognosis of IOL replacement. Methods: Forty medical records (42 eyes) of patients with US-860UV IOL opacification reporting decreased or lost vision who underwent IOL explantation between 2017 and 2019 were reviewed. Explanted IOLs were analyzed by slit-lamp examination, confocal microscopy, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) at the Shandong Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University, and Qingdao University of Science and Technology, Qingdao, China. Results: The mean age of the 40 patients was 74.83 â€‹± â€‹7.57 (63-92) years. The mean interval between cataract surgery and diagnosis of opacification was 32.38 â€‹± â€‹8.76 (17-48) months. Systemic diseases were found without statistical correlations, the most frequent being arterial hypertension, coronary heart disease, and diabetes mellitus. Visual acuity improved from 1.42 â€‹± â€‹1.03 to 0.31 â€‹± â€‹0.16 (logMAR) after IOL replacement. SEM, EDS and alizarin red staining showed uniformly distributed, diffuse, milk-white opacification, with calcium and phosphorus deposits on the optic and haptic surfaces that could be dissolved in 1% HCl. Conclusions: Calcium and phosphorus deposition was the main cause of hydrophilic acrylic US-860UV IOL opacification. IOL replacement can safely and effectively improve the visual acuity of patients.

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