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1.
Am J Ophthalmol Case Rep ; 36: 102168, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39319201

RESUMEN

Purpose: We present a case of macular hole retinal detachment (MHRD) in a patient with Straatsma syndrome, a rare condition characterized by extensive unilateral myelinated retinal nerve fibers (MRNF), high myopia, and amblyopia. This study aimed to highlight the clinical presentations, diagnostic challenges, and success of surgical interventions. Observation: A 32-year-old Asian woman with a history of high myopia and poorly corrected vision in her right eye since childhood presented with a sudden loss of vision in the right eye. Examination revealed extensive MRNF and retinal detachment with a macular hole. A standard three-port pars plana vitrectomy was performed, and tight vitreous retinal adhesions were observed. PFCL-assisted inverted internal limiting membrane (ILM) flap technique was performed. Silicone oil was used owing to its tight vitreous retinal adhesion. Postoperatively, the macular hole was closed, the retina was reattached, and partial disappearance of the MRNF was observed. Conclusion and importance: This case report describes a successful surgical intervention for MHRD associated with Straatsma syndrome. The PFCL-assisted inverted ILM flap technique is effective for managing complicated cases of MHRD. The partial disappearance of MRNF after vitrectomy suggests potential nerve fiber layer damage, possibly due to retinal detachment or the use of silicone oil. This case highlights the unique features of MHRD, a rare disease associated with Straatsma syndrome.

2.
J Clin Med ; 13(11)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38892762

RESUMEN

Objectives: Ophthalmic three-dimensional (3D) digital surgery can reproduce high-definition surgical images; however, 3D digital surgery is limited by recording capacities. We examined the relationship between the minimum image quality required to reproduce surgical images and recording capacity. Methods: Patients who underwent simultaneous vitrectomy and cataract surgery by the same surgeon using a 3D digital surgery system at Juntendo University Urayasu Hospital between February and October 2021 were evaluated. Various quality (Q) and frame rate (FR) settings were used for each case. Four vitreous surgeons evaluated the reproducibility of recorded images of macular manipulation for epiretinal membrane (ERM) and macular hole (MH) cases and those of peripheral retinal manipulation for rhegmatogenous retinal detachment (RRD) cases. The video bitrate and minimum settings required to reproduce surgical images and factors affecting surgical image reproducibility were examined. Results: A total of 129 eyes of 129 patients were observed. The minimum image quality required to reproduce surgical images was 11.67 Mbps. The Q and FR for periretinal processing and Q for macular manipulation affected surgical image reproducibility (p = 0.025, p = 0.019, and p = 0.07, respectively). The minimum recording settings required to obtain highly reproducible images were Q = 3 and FR = 40. The total file size for vitrectomy video recordings with these settings was as compact as 3.17 GB for 28 min. Conclusions: During 3D digital surgery, highly reproducible surgical images can be obtained with a small storage capacity using settings of at least Q = 3 and FR = 40.

3.
Glia ; 71(10): 2372-2382, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37335016

RESUMEN

In the retina, microglia are resident immune cells that are essential for development and function. Retinal microglia play a central role in mediating pathological degeneration in diseases such as glaucoma, retinitis pigmentosa, age-related neurodegeneration, ischemic retinopathy, and diabetic retinopathy. Current models of mature human retinal organoids (ROs) derived from iPS cell (hiPSC) do not contain resident microglia integrated into retinal layers. Increasing cellular diversity in ROs by including resident microglia would more accurately represent the native retina and better model diseases in which microglia play a key role. In this study, we develop a new 3D in vitro tissue model of microglia-containing retinal organoids by co-culturing ROs and hiPSC-derived macrophage precursor cells (MPCs). We optimized the parameters for successful integration of MPCs into retinal organoids. We show that while in the ROs, MPCs migrate to the equivalent of the outer plexiform layer where retinal microglia cells reside in healthy retinal tissue. While there, they develop a mature morphology characterized by small cell bodies and long branching processes which is only observed in vivo. During this maturation process these MPCs cycle through an activated phase followed by a stable mature microglial phase as seen by the down regulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. Finally, we characterized mature ROs with integrated MPCs using RNAseq showing an enrichment of cell-type specific microglia markers. We propose that this co-culture system may be useful for understanding the pathogenesis of retinal diseases involving retinal microglia and for drug discovery directly in human tissue.


Asunto(s)
Células Madre Pluripotentes Inducidas , Enfermedades de la Retina , Humanos , Células Madre Pluripotentes Inducidas/patología , Microglía/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Retina , Enfermedades de la Retina/patología , Organoides/patología , Macrófagos/patología , Citocinas/metabolismo
4.
Jpn J Ophthalmol ; 67(4): 431-439, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37079165

RESUMEN

PURPOSE: Galectin-3 is a damage-associated molecular pattern (DAMPs), released from damaged or dying cells. In this study, we investigated the concentration and source of galectin-3 in the tears of patients with vernal keratoconjunctivitis (VKC) and evaluated whether the concentration of galectin-3 in tears represents a biomarker of corneal epithelial damage. STUDY DESIGN: Clinical and experimental. METHODS: We measured the concentration of galectin-3 in tear samples from 26 patients with VKC and 6 healthy controls by enzyme-linked immunosorbent assay (ELISA). The expression of galectin-3 in cultured human corneal epithelial cells (HCEs) stimulated with or without tryptase or chymase was investigated by polymerase chain reaction (PCR), ELISA, and Western blotting. We also estimated the concentration of galectin-3 in the supernatants of cultured HCEs induced to necrosis. Finally, we investigated whether recombinant galectin-3 induced the expression of various genes related to cell migration or the cell cycle in HCEs by using microarray analysis. RESULTS: High concentrations of galectin-3 were detected in the tears of patients with VKC. The concentration showed significant correlation with the severity of corneal epithelial damage. Stimulation of cultured HCEs with various concentrations of tryptase or chymase had no effect on the expression of galectin-3. However, high concentrations of galectin-3 were detected in the supernatants of necrotic HCEs. Recombinant human galectin-3 induced various cell migration- and cell cycle-related genes. CONCLUSION: The concentrations of galectin-3 in the tears of patients with VKC may represent a biomarker of the severity of corneal epithelial damage.


Asunto(s)
Conjuntivitis Alérgica , Humanos , Quimasas/metabolismo , Conjuntivitis Alérgica/diagnóstico , Conjuntivitis Alérgica/genética , Conjuntivitis Alérgica/metabolismo , Ensayo de Inmunoadsorción Enzimática , Galectina 3/genética , Galectina 3/metabolismo , Lágrimas/metabolismo , Triptasas/metabolismo
5.
Invest Ophthalmol Vis Sci ; 63(13): 26, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36580308

RESUMEN

Purpose: Vernal keratoconjunctivitis (VKC) is a severe, recurrent allergic conjunctivitis. Previously, we found high concentrations of oncostatin M (OSM) in the tears of patients with VKC. Here, we investigated the role of OSM in VKC by focusing on epithelial barrier function and IL-33 production. Methods: To assess the effect of OSM on the barrier function of human conjunctival epithelial cells (HConEpiCs), we measured transepithelial electrical resistance and dextran permeability. We also assessed expression of tight junction-related proteins such as E-cadherin and ZO-1 in HConEpiCs by Western blotting and immunofluorescence. Then we used immunohistochemistry to evaluate expression of Ki-67, E-cadherin, epithelial-mesenchymal transition-related proteins, and IL-33 in giant papillae (GPs) from patients with VKC. In addition, we used Western blotting, microarray, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay to examine whether OSM activates signal transducer and activator of transcription 1 (STAT1) or STAT3 and induces the expression of various genes in human conjunctival fibroblasts (HConFs). Results: OSM reduced expression of E-cadherin and ZO-1 in HConEpiCs, indicating barrier dysfunction. In immunohistochemistry, Ki-67 expression was present in the lower epithelial layer of the GPs, and E-cadherin expression was reduced in the superficial and lower layers; double staining revealed that GPs had a high number of fibroblasts expressing IL-33. In addition, in HConFs, OSM phosphorylated both STAT1 and STAT3 and induced IL-33. Conclusions: OSM has important roles in severe, prolonged allergic inflammation by inducing epithelial barrier dysfunction and IL-33 production by conjunctival fibroblasts.


Asunto(s)
Conjuntivitis Alérgica , Humanos , Conjuntivitis Alérgica/metabolismo , Oncostatina M/metabolismo , Oncostatina M/farmacología , Interleucina-33 , Antígeno Ki-67/metabolismo , ARN Mensajero/genética , Epitelio/metabolismo , Fibroblastos/metabolismo , Cadherinas/metabolismo
6.
BMC Ophthalmol ; 22(1): 458, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36447155

RESUMEN

BACKGROUND: Macular edema is found in more than half of branch retinal vein occlusion (BRVO) cases, leading to visual loss in most of these cases. Intravitreal injection of anti-vascular endothelial growth factor is currently the standard treatment for macular edema due to BRVO (BRVO-ME). The difference in the effects of aflibercept and ranibizumab on the choroid in BRVO-ME is unknown. Therefore, we analyzed the effects of intravitreal injection of ranibizumab and aflibercept on BRVO-ME. METHODS: We retrospectively observed changes in choroidal thickness in the subfoveal region in 36 patients with BRVO-ME who visited the Department of Ophthalmology at the Juntendo University Urayasu Hospital. The patients were treated with intravitreal injection of aflibercept or ranibizumab and followed up for 12 months or more. RESULTS: The observed point bifurcated into the affected and non-affected sides 500 µm from the fovea. The central macular thickness (CMT) and subfoveal choroidal thickness (SFCT) were 564.2 ± 268.5 µm and 228.8 ± 50.1 µm, respectively, in the ranibizumab group (16 patients, 16 eyes) and 542.4 ± 172.5 µm and 246.1 ± 59.1 µm, respectively, in the aflibercept group (20 patients, 20 eyes). The changes in CMT at 12 months were 324.0 ± 262.6 µm and 326.55 ± 187.2 µm in the ranibizumab and aflibercept groups, respectively, with no significant difference (p = 0.97). Similarly, the changes in SFCT over 12 months were not significant between the groups (ranibizumab, 41.9 ± 33.0 µm; aflibercept, 43.8 ± 43.8 µm, p = 0.89). CONCLUSION: The effects of ranibizumab and aflibercept on choroidal thickness in BRVO-ME were the same regardless of the site. Although BRVO is a retinal disease, we hope that we can further explore the mechanism of BRVO-ME by observing changes in the choroid in the future.


Asunto(s)
Edema Macular , Oclusión de la Vena Retiniana , Humanos , Ranibizumab/uso terapéutico , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Inyecciones Intravítreas , Estudios Retrospectivos , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Coroides
7.
JCI Insight ; 7(12)2022 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-35639473

RESUMEN

Disruption of the neurovascular unit (NVU) underlies the pathophysiology of various CNS diseases. One strategy to repair NVU dysfunction uses stem/progenitor cells to provide trophic support to the NVU's functionally coupled and interdependent vasculature and surrounding CNS parenchyma. A subset of endothelial progenitor cells, endothelial colony-forming cells (ECFCs) with high expression of the CD44 hyaluronan receptor (CD44hi), provides such neurovasculotrophic support via a paracrine mechanism. Here, we report that bioactive extracellular vesicles from CD44hi ECFCs (EVshi) are paracrine mediators, recapitulating the effects of intact cell therapy in murine models of ischemic/neurodegenerative retinopathy; vesicles from ECFCs with low expression levels of CD44 (EVslo) were ineffective. Small RNA sequencing comparing the microRNA cargo from EVshi and EVslo identified candidate microRNAs that contribute to these effects. EVshi may be used to repair NVU dysfunction through multiple mechanisms to stabilize hypoxic vasculature, promote vascular growth, and support neural cells.


Asunto(s)
Células Progenitoras Endoteliales , Vesículas Extracelulares , MicroARNs , Enfermedades de la Retina , Animales , Células Progenitoras Endoteliales/metabolismo , Vesículas Extracelulares/metabolismo , Isquemia/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Neovascularización Fisiológica/fisiología , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/terapia
8.
Glia ; 70(9): 1762-1776, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35611927

RESUMEN

Retinal neovascularization (NV) is the major cause of severe visual impairment in patients with ischemic eye diseases. While it is known that retinal microglia contribute to both physiological and pathological angiogenesis, the molecular mechanisms by which these glia regulate pathological NV have not been fully elucidated. In this study, we utilized a retinal microglia-specific Transforming Growth Factor-ß (Tgfß) receptor knock out mouse model and human iPSC-derived microglia to examine the role of Tgfß signaling in activated microglia during retinal NV. Using a tamoxifen-inducible, microglia-specific Tgfß receptor type 2 (Tgfßr2) knockout mouse [Tgfßr2 KO (ΔMG)] we show that Tgfß signaling in microglia actively represses leukostasis in retinal vessels. Furthermore, we show that Tgfß signaling represses expression of the pro-angiogenic factor, Insulin-like growth factor 1 (Igf1), independent of Vegf regulation. Using the mouse model of oxygen-induced retinopathy (OIR) we show that Tgfß signaling in activated microglia plays a role in hypoxia-induced NV where a loss in Tgfß signaling microglia exacerbates and prolongs retinal NV in OIR. Using human iPSC-derived microglia cells in an in vitro assay, we validate the role of Transforming Growth Factor-ß1 (Tgfß1) in regulating Igf1 expression in hypoxic conditions. Finally, we show that Tgfß signaling in microglia is essential for microglial homeostasis and that the disruption of Tgfß signaling in microglia exacerbates retinal NV in OIR by promoting leukostasis and Igf1 expression.


Asunto(s)
Leucostasis , Enfermedades de la Retina , Neovascularización Retiniana , Animales , Modelos Animales de Enfermedad , Hipoxia/complicaciones , Hipoxia/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Leucostasis/complicaciones , Leucostasis/metabolismo , Leucostasis/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , Neovascularización Patológica/metabolismo , Oxígeno/metabolismo , Enfermedades de la Retina/metabolismo , Neovascularización Retiniana/etiología , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Factor de Crecimiento Transformador beta/metabolismo
9.
Life (Basel) ; 12(2)2022 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-35207471

RESUMEN

Retinal diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP), are some of the leading causes of blindness all over the world [...].

10.
Life (Basel) ; 11(11)2021 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-34832995

RESUMEN

Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.

11.
Jpn J Ophthalmol ; 65(1): 144-153, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33403505

RESUMEN

PURPOSE: Vernal keratoconjunctivitis (VKC) is a severe and recurrent allergic conjunctivitis, the mechanism of which is not well understood. In this study, we investigated the role of oncostatin M (OSM) in the pathogenesis of VKC, with a focus on tissue remodeling. STUDY DESIGN: Clinical and experimental. PATIENTS AND METHODS: The OSM concentrations in tear fluid samples obtained from VKC patients and healthy controls were measured using ELISA, and the expression of OSM mRNA and protein in giant papillae resected from VKC patients was investigated using RT-PCR and immunohistochemistry, respectively. In cultured human conjunctival epithelial cells (HconEpiCs), expression of OSM receptor ß (OSMRß) was detected using immunocytochemical and FACS analyses. Finally, we investigated whether recombinant OSM activated STAT1 and STAT3 to induce the expression of various genes related to tissue remodeling in HconEpiCs, by using Western blot analysis, microarray analysis, and RT-PCR. RESULTS: The OSM concentration was higher in the tear fluid of VKC patients than in that of the healthy controls, and strong expression of OSM mRNA was found in the giant papillae. We also detected T cells expressing OSM in the giant papillae. In addition, HconEpiCs showed surface expression of OSMRß. Recombinant human OSM strongly activated both STAT1 and STAT3 in HconEpiCs and induced various tissue remodeling-related genes, including MMP-1, MMP-3, IL-24, IL-20, serpinB3, S100A7, tenascin C, and SOCS3. CONCLUSION: Our results suggest that OSM is one of the key molecules involved in remodeling of giant papillae in VKC.


Asunto(s)
Conjuntivitis Alérgica , Conjuntiva , Conjuntivitis Alérgica/diagnóstico , Humanos , Oncostatina M/genética , ARN Mensajero , Lágrimas
12.
Life (Basel) ; 11(2)2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33503815

RESUMEN

Diabetic macular edema (DME) is a common cause of visual impairment in patients with diabetes. Although intravitreal anti-vascular endothelial growth factor (VEGF) injections were efficacious in clinical trials, several patients exhibited a poor response. This study aimed to compare clinical features between patients who were susceptible to intravitreal anti-VEGF injections for DME and those who were not. A single-center, retrospective study of 102 such patients was conducted (123 eyes; mean ± standard deviation age, 63.4 ± 10.8 years; 57.8% males). Systemic and ocular data, assessed at baseline and after a month, were compared between good (>20% decrease in central macular thickness (CMT)) and poor (≤20% decrease in CMT) responders using the Mann-Whitney U test/Fisher's exact test. Eighty-one eyes (65.9%) were good responders. The glycosylated hemoglobin level was higher (p = 0.011) in poor (7.5% ± 0.94%) than in good (7.04% ± 1.19%) responders. The foveal avascular zone was larger (p = 0.0003) in poor (0.67 ± 0.33 µm2) than in good (0.47 ± 0.23 µm2) responders. The number of microaneurysms in the pericapillary network was higher (p = 0.0007) in poor (2.7 ± 2.2) than in good (1.4 ± 2.0) responders. Baseline glycemic control and macular ischemia may be associated with the short-term response to intravitreal anti-VEGF injections.

13.
Proc Natl Acad Sci U S A ; 117(45): 28297-28306, 2020 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-33106407

RESUMEN

Retinal neovascularization (NV), a leading cause of vision loss, results from localized hypoxia that stabilizes the hypoxia-inducible transcription factors HIF-1α and HIF-2α, enabling the expression of angiogenic factors and genes required to maintain homeostasis under conditions of oxygen stress. HIF transcriptional activity depends on the interaction between its intrinsically disordered C-terminal domain and the transcriptional coactivators CBP/p300. Much effort is currently directed at disrupting protein-protein interactions between disease-associated transcription factors like HIF and their cellular partners. The intrinsically disordered protein CITED2, a direct product of HIF-mediated transcription, functions as a hypersensitive negative regulator that attenuates the hypoxic response by competing allosterically with HIF-1α for binding to CBP/p300. Here, we show that a peptide fragment of CITED2 is taken up by retinal cells and efficiently regulates pathological angiogenesis in murine models of ischemic retinopathy. Both vaso-obliteration (VO) and NV were significantly inhibited in an oxygen-induced retinopathy (OIR) model following intravitreal injection of the CITED2 peptide. The CITED2 peptide localized to retinal neurons and glia, resulting in decreased expression of HIF target genes. Aflibercept, a commonly used anti-VEGF therapy for retinal neovascular diseases, rescued NV but not VO in OIR. However, a combination of the CITED2 peptide and a reduced dose of aflibercept significantly decreased both NV and VO. In contrast to anti-VEGF agents, the CITED2 peptide can rescue hypoxia-induced retinal NV by modulating the hypoxic response through direct competition with HIF for CBP/p300, suggesting a dual targeting strategy for treatment of ischemic retinal diseases and other neovascular disorders.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/efectos de los fármacos , Hipoxia/metabolismo , Péptidos/metabolismo , Proteínas Represoras/metabolismo , Neovascularización Retiniana/metabolismo , Transactivadores/metabolismo , Animales , Proteína p300 Asociada a E1A/metabolismo , Expresión Génica , Células HEK293 , Humanos , Proteínas Intrínsecamente Desordenadas/metabolismo , Ratones , Ratones Endogámicos C57BL , Oxígeno/metabolismo , Dominios y Motivos de Interacción de Proteínas , Proteínas Represoras/genética , Transactivadores/genética , Factores de Transcripción p300-CBP/metabolismo
14.
JCI Insight ; 5(12)2020 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-32437334

RESUMEN

Abnormal subretinal neovascularization is a characteristic of vision-threatening retinal diseases, including macular telangiectasia (MacTel) and retinal angiomatous proliferation (RAP). Subretinal neovascular tufts and photoreceptor dysfunction are observed in very-low-density lipoprotein receptor (Vldlr-/-) mutant mice. These changes mirror those observed in patients with MacTel and RAP, but the pathogenesis is largely unknown. In this study, we show that retinal microglia were closely associated with retinal neovascular tufts in Vldlr-/- mice and retinal tissue from patients with MacTel; ablation of microglia/macrophages dramatically prevented formation of retinal neovascular tufts and improved neuronal function, as assessed by electroretinography. Vldlr-/- mice with retinal pigmented epithelium-specific (RPE-specific) Vegfa had greatly reduced subretinal infiltration of microglia/macrophages, subsequently reducing neovascular tufts. These findings highlight the contribution of microglia/macrophages to the pathogenesis of neovascularization, provide valuable clues regarding potential causative cellular mechanisms for subretinal neovascularization in patients with MacTel and RAP and suggest that targeting microglia activation may be a therapeutic option in these diseases.


Asunto(s)
Degeneración Macular/patología , Microglía/patología , Neovascularización Retiniana/patología , Epitelio Pigmentado de la Retina/patología , Animales , Modelos Animales de Enfermedad , Ratones Noqueados , Neovascularización Patológica/patología , Retina/patología , Vasos Retinianos/patología
16.
Int Immunopharmacol ; 52: 70-76, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28866026

RESUMEN

A randomized clinical trial showed the beneficial effects of the selective peroxisome proliferator-activated receptor (PPAR)-α agonist, fenofibrate, in reducing the progression of diabetic retinopathy independent of serum lipid levels. All subtypes of PPAR (PPAR-α, PPAR-γ, and PPAR-ß/δ) have been reported to play a key role in microvascular inflammation and angiogenesis. Therefore, the agonistic function of fenofibrate against the PPAR-α has been suggested to contribute to its medicinal effect. Furthermore, bezafibrate is a fibrate drug commonly used as a lipid-lowering agent to treat hyperlipidemia and acts as a pan-agonist of all PPARs subtypes. However, the effects of bezafibrate in diabetic retinopathy remain unclear. Therefore, the purpose of this study was to investigate the effects of bezafibrate on retinal microvascular inflammation. Bezafibrate was not cytotoxic against human retinal microvascular endothelial cells (HRMECs) and human retinal pigment epithelial cells (ARPE-19 cells) treated with <100 and 200µM bezafibrate, respectively. In HRMECs, the expression levels of tumor necrosis factor (TNF)-α-induced monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 were significantly suppressed by bezafibrate in a dose-dependent manner. TNF-α-induced nuclear translocation of nuclear factor (NF)-κB p65 and cell migration were also significantly inhibited in bezafibrate-treated HRMECs. Furthermore, bezafibrate treatment significantly suppressed interleukin (IL)-1ß-induced vascular endothelial growth factor (VEGF) production in ARPE-19 cells. These results suggest that bezafibrate has beneficial effects on retinal microvascular inflammation. Our study demonstrates the therapeutic potential of bezafibrate for managing diabetic retinopathy.


Asunto(s)
Antiinflamatorios/farmacología , Bezafibrato/farmacología , Retinopatía Diabética/tratamiento farmacológico , Células Endoteliales/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Receptores Activados del Proliferador del Peroxisoma/agonistas , Retina/patología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Células Cultivadas , Quimiocina CCL2/metabolismo , Retinopatía Diabética/inmunología , Células Endoteliales/inmunología , Humanos , FN-kappa B/metabolismo , Epitelio Pigmentado de la Retina/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
17.
Mediators Inflamm ; 2017: 3124753, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28751819

RESUMEN

Numerous mast cells are present in the choroid, but the effects of mast cell mediators on retinal pigment epithelial (RPE) cells are not well understood. We investigated the influence of mast cell mediators on RPE cells in vitro, focusing on tryptase. Expression of receptors was examined by the reverse transcription polymerase chain reaction. We also assessed production of interleukin 8 and vascular endothelial growth factor (VEGF) after RPE cells were stimulated with mast cell mediators by using an antibody array and enzyme-linked immunosorbent assay. Furthermore, we investigated the influence of tryptase on RPE cell migration and integrity by the scratch assay and the transepithelial resistance. RPE cells expressed protease-activated receptor 2 (PAR2), histamine receptor 1, tumor necrosis factor-α (TNF-α) receptor 1, and CCR 1, 3, 4, 8, and 11. Tryptase, PAR2 agonists, histamine, and TNF-α all enhanced interleukin 8 production by RPE cells, while only tryptase enhanced VEGF production. Tryptase also enhanced expression of phosphorylated extracellular signal-regulated kinases 1/2, resulting in increased migration of RPE cells. However, tryptase did not alter epithelial integrity or the expression of zonula occludens-1 and junctional adhesion molecule-A by RPE cells. Mast cell mediators, especially tryptase, may influence RPE cell inflammation.


Asunto(s)
Células Epiteliales/citología , Células Epiteliales/metabolismo , Mastocitos/citología , Mastocitos/metabolismo , Pigmentos Retinianos/metabolismo , Triptasas/metabolismo , Línea Celular , Movimiento Celular/fisiología , Ensayo de Inmunoadsorción Enzimática , Liberación de Histamina/fisiología , Humanos , Inmunohistoquímica , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
18.
Clin Ophthalmol ; 11: 829-834, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28496301

RESUMEN

PURPOSE: The purpose of this study was to determine the short-term outcomes for patients who received intravitreal aflibercept (IVA) with or without intravitreal ranibizumab (IVR) for macular edema (ME) due to branch retinal vein occlusion (BRVO). PATIENTS AND METHODS: Patients received IVA for ME due to BRVO. Patients who initially received IVA were defined as the treatment-naïve group and those who were switched from IVR to IVA after ME recurrence were defined as the switching group. Patient outcomes were examined at 1 week and 1 month postinjection. RESULTS: Both groups comprised 27 eyes from 27 patients. There was a significant decrease in central macular thickness (CMT) at 1 week and 1 month postinjection in both groups. There was also a significant improvement in best-corrected visual acuity (BCVA) at 1 week and 1 month postinjection in the treatment-naïve group and 1 month in the switching group. Younger age was associated with a good BCVA at 1 month postinjection in the switching group, and the absence of epiretinal membrane was associated with a reduction in CMT at 1 month postinjection in the switching group. CONCLUSION: IVA is temporarily effective for treating ME due to BRVO regardless of a history of IVR use.

19.
Invest Ophthalmol Vis Sci ; 57(11): 4999-5005, 2016 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-27661853

RESUMEN

PURPOSE: The purpose of this study was to investigate whether fibrocytes participate in formation of the fibrovascular membrane (FVM) in patients with proliferative diabetic retinopathy (PDR). METHODS: Vitreous fluid and FVM samples were obtained during vitrectomy in patients with PDR. Samples from patients with macular hole or epiretinal membrane were used as controls. Vitreous fluid and FVM samples were subjected to immunohistochemical analysis. In addition, cells isolated from the vitreous fluid of PDR and control patients were cultured in serum-free medium. Fibrocytes were identified among these cells by morphological and immunohistochemical analyses. We examined the number of fibrocytes in PDR patients and control patients. Also, the concentrations of monocyte chemoattractant protein-1 (MCP-1), pentraxin3, and serum amyloid P (SAP) in vitreous fluid samples from PDR patients and control patients were determined by enzyme-linked immunosorbent assay. RESULTS: Fibrocytes were observed in the vitreous and FVM samples from PDR patients. Cells cultured from the vitreous samples of PDR patients were spindle shaped and expressed fibrocyte markers. TGF-ß1 induced differentiation of these cells into myofibroblasts. The number of fibrocytes was higher in samples from PDR patients than in samples from control patient. The vitreous fluid concentration of MCP-1 was significantly higher in PDR patients than in controls and showed a significant positive correlation with the number of fibrocytes from the vitreous fluid. Vitreous fluid concentrations of pentraxin3 and SAP were also higher in PDR patients than in control patients. CONCLUSIONS: These findings indicate that fibrocytes may be involved in development of the FVM in PDR.

20.
Clin Ophthalmol ; 10: 1161-5, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27382250

RESUMEN

PURPOSE: The purpose of this study was to determine the clinical efficacy of low-frequency intravitreal ranibizumab to treat macular edema due to retinal vein occlusion (RVO). PATIENTS AND METHODS: This was a retrospective examination of cases that received intravitreal ranibizumab for untreated RVO over a period of 12 months. Instead of the conventional three monthly injections, injections were given once during the introductory period. If the recurrence of macular edema was diagnosed during the monthly visit, additional injections were given as needed. There were 21 eyes of 21 patients with branch RVO (BRVO) and ten eyes of ten patients with central RVO (CRVO). The parameters examined included the number of injections over the 12-month period, improvements in best-corrected visual acuity (BCVA), and the central macular thickness (CMT). For BRVO, preinjection parameters that had an effect on the prognosis of BCVA after the 12-month period were also examined. RESULTS: The total mean number of injections over the 12-month period was 3.4 for CRVO and 2.1 for BRVO. For CRVO, the BCVA in log minimum angular resolution changed from a preinjection value of 0.80 to 0.55 at 12 months. For BRVO, the change was from 0.51 to 0.30. For all diseases, BCVA improved after 12 months compared with the preinjection values (P<0.05). There was improvement in the CMT, and the CRVO changed from 765.0 µm at preinjection to 253.5 µm 12 months later. BRVO changed from 524.1 to 250.1 µm, and pre-injection BCVA was associated with a prognosis of visual acuity after 12 months of the initial injection (P=0.0485). CONCLUSION: Even with a low number of injections during the introductory period, there were still improvements in both visual acuity and CMT in RVO patients after 12 months, indicating that it was an effective treatment.

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