RESUMO
SIGNIFICANCE: Central serous chorioretinopathy (CSC) is a common retinal disease that causes vision loss worldwide. Studying the imaging characteristics of CSC is helpful for the differential diagnosis of diseases. This study analyzed the differences between acute and chronic CSC and provide related information. PURPOSE: The aim of this study was to describe the optical coherence tomography features in patients with acute and chronic CSC. METHODS: Sixty-two eyes of 56 patients with CSC were included in the study. Optical coherence tomography was performed to observe the image features. The photoreceptor outer-segment (PROS) thickness above the pigment epithelium detachment (PED) coinciding with the leakage point in fundus fluorescein angiography was measured and compared with the mean PROS thickness outside the PED in acute cases. The SPSS 23.0 software (IBM Co., Chicago, IL) was used for statistical analysis. RESULTS: Of our 56 patients (62 eyes), 41 (73.21%) were male and 15 (26.79%) were female. There were 53 eyes (85.48%) with acute CSC and 9 eyes (14.52%) with chronic CSC. Besides other common features, the new feature of a high-reflection band in the outer nuclear layer was found to be limited to the macular detachment area. In acute cases, the mean PROS thickness above the retinal pigment epithelium layer protuberance coinciding with the leakage point was 22.7 ± 8.8 µm, which was less than the mean PROS thickness outside the PED at 64.3 ± 21.3 µm (P ≤ .001). CONCLUSIONS: The high-reflection band in the outer nuclear layer within the serous neurosensory detachment limited to the macular area was a new finding in CSC patients. This finding can be used as an imaging feature to aid in the diagnosis of CSC.
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Coriorretinopatia Serosa Central , Descolamento Retiniano , Coriorretinopatia Serosa Central/diagnóstico por imagem , Feminino , Angiofluoresceinografia/métodos , Humanos , Masculino , Retina , Descolamento Retiniano/diagnóstico por imagem , Epitélio Pigmentado da Retina/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: We report one case of rare acute macular neuroretinopathy (AMN) in an elderly patient with hypertension and one case of common paracentral acute middle maculopathy (PAMM) in a patient with diabetes mellitus to illustrate the difference between the two diseases. CASE PRESENTATION: This report describes two cases, one involving AMN and the other PAMM. The first patient was a 70-year-old man complaining of blurred vision for 3 days. He was examined with fundus photography, optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT); a diagnosis of AMN was established. The second patient was a 50-year-old woman who complained of decreased vision during the past month. She had had diabetes mellitus for 6 years. From the ophthalmic imaging examination, the patient was diagnosed with PAMM and non-proliferative diabetic retinopathy (NPDR). Both patients were treated with drugs for improving microcirculation and neurotrophic drugs; however, there was no significant improvement in visual acuity. CONCLUSIONS: AMN is more common in young patients and is rarely observed in elderly patients with systemic diseases. The OCTA examination has an auxiliary diagnostic value for deep retinal capillary network ischaemia. Meanwhile, OCT examination has important imaging value in differentiating AMN from PAMM and can help avoid missed diagnoses.
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Degeneração Macular , Doenças Retinianas , Síndrome dos Pontos Brancos , Doença Aguda , Idoso , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/diagnóstico , Tomografia de Coerência ÓpticaRESUMO
Diabetic retinopathy (DR) is a microvascular complication of diabetes and one of the most common causes of blindness in active stage. This study is performed to explore the effects of microRNA-21 (miR-21) on retinal vascular endothelial cell (RVEC) viability and angiogenesis in rats with DR via the phosphatidylinositiol 3-kinase/protein kinase B (PI3K/Akt)/vascular endothelial growth factor (VEGF) signaling pathway by binding to phosphatase and tensin homolog (PTEN). Sprague Dawley (SD) rats were used for establishment of DR models. Target relationship between miR-21 and PTEN was assessed by bioinformatics prediction in combination with dual-luciferase reporter gene assay. Identification of expression of miR-21, PTEN and PI3K/Akt/VEGF signaling pathway-related genes in the retinal tissues was then conducted. In order to assess the contributory role of miR-21 in DR, the RVECs were transfected with mimic or inhibitor of miR-21, or siRNA-PTEN, followed by the detection of expression of PTEN and PI3K/Akt/VEGF-related genes, as well as the measurement of cell viability, cell cycle and apoptosis. Increased expression of miR-21 and PI3K/Akt/VEGF related genes, along with a reduced expression of PTEN was observed in the retinal tissues of DR rats. PTEN was targeted and negatively regulated by miR-21, while the PI3K/Akt/VEGF signaling pathway was activated by miR-21. RVECs transfected with miR-21 inhibitor exhibited promoted viability and angiogenesis, and inhibited apoptosis. To conclude, our results indicated that miR-21 overexpression could potentially stimulate RVEC viability and angiogenesis in rats with DR through activation of the PI3K/Akt/VEGF signaling pathway via repressing PTEN expression, highlighting the potential of miR-21 as a target for DR treatment.
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Retinopatia Diabética/metabolismo , Células Endoteliais/patologia , MicroRNAs/genética , Neovascularização Patológica/prevenção & controle , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose , Western Blotting , Proliferação de Células , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/genética , Células Endoteliais/metabolismo , Repressão Epigenética/fisiologia , Citometria de Fluxo , Imuno-Histoquímica , Masculino , Neovascularização Patológica/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Vasos Retinianos/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia , Transfecção , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
PURPOSE: To identify the spectral domain optical coherence tomography predictors of visual prognosis in retinal vein occlusion macular edema after intravitreal conbercept injection. METHODS: Retrospective cohort study of 63 treatment-naive retinal vein occlusion macular edema eyes received pro re nata intravitreal conbercept with at least 3 months of follow-up. The best-corrected visual acuity (BCVA) and optical coherence tomography scans were recorded at baseline, 1 month, and 3 months after starting therapy. On spectral domain optical coherence tomography, the following lesions in the 1-mm-wide retinal area centered on the fovea: disorganization of the retinal inner layer extent, cysts, hyperreflective foci, microaneurysms, external limiting membrane or ellipsoid zone disruption, foveal bulge, and foveal depression were evaluated by masked graders. Regression analysis was used to determine independent predictors of BCVA at 1- and 3-month follow-up. RESULTS: The thicker central subfield thickness, greater extent of external limiting membrane disruption, and presence of hyperreflective foci >20 at baseline were correlated with the worse baseline BCVA (all P < 0.05). The greater extent of external limiting membrane disruption and presence of hyperreflective foci >20 at baseline were associated with poorer BCVA during follow-up (all P < 0.05). The central subfield thickness and extent of ellipsoid zone disruption at baseline and their changes over time were correlated with the 3-month BCVA improvement (all P < 0.05). Furthermore, changes in the ellipsoid zone disruption extent or central subfield thickness after 1 month identified eyes with a high likelihood of subsequent BCVA improvement or decline. CONCLUSION: The external limiting membrane status and hyperreflective foci >20 at baseline could be good predictors for short-term visual outcome, whereas the central subfield thickness and ellipsoid zone status at baseline and their changes over time may predict visual improvement in patients with retinal vein occlusion macular edema after intravitreal conbercept injection.
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Angiofluoresceinografia/métodos , Macula Lutea/patologia , Edema Macular/diagnóstico , Proteínas Recombinantes de Fusão/administração & dosagem , Oclusão da Veia Retiniana/complicações , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Feminino , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: To evaluate the etiology of lacrimal canalicular laceration and explore the possible risk factors influencing prognosis. METHODS: The data of 142 patients (142 eyes) with lacrimal canalicular lacerations who were surgically treated using canalicular anastomosis combined with bicanalicular stent intubation between March 2017 and March 2018 were reviewed. The analyzed data contained demographic information, types of trauma, injury locations, associated additional ocular injuries, and surgical outcomes at follow-up. The main outcome measures were anatomic success rate, functional success rate, and complications of surgery. RESULTS: The mean patient age was 42.07 years (ranging from 1 to 75 years). Among the 142 patients, 112 (78.87%) were males. Upper and lower canalicular lacerations were found in 14 (9.86%) and 112 (78.87%) patients, respectively. Meanwhile, both upper and lower canalicular lacerations were found in 16 (11.27%) patients. Electric bike accidents comprised the leading cause of injury, accounting for 76 (53.52%) cases. There were 100 (70.42%) patients who had lid lacerations without tarsal plate fracture and 42 (29.58%) patients who had lid lacerations with tarsal plate fractures. The anatomic success rate was 98.59% and the functional success rate was 83.8%. The functional reconstruction failure rates were higher in patients with indirect injuries, lid lacerations with tarsal plate fractures, and those with punctum splitting (P < 0.05). Surgical complications were detected in the form of lacrimal punctum ectropion in 3 (2.11%) patients, punctum splitting in 2 (1.41%) patients, and stent extrusion and loss in 2 (1.41%) patients. CONCLUSIONS: Electric bike accidents have become the leading cause of injury instead of motor vehicle accidents because of the changes in the lifestyles of people. Indirect injuries, lid lacerations with tarsal plate fractures, and those with punctum splitting were significantly more likely to lead to poor prognosis, as confirmed by the lower functional success rate of surgery.
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Lacerações , Aparelho Lacrimal , Adulto , Anastomose Cirúrgica , Feminino , Humanos , Intubação , Intubação Intratraqueal , Lacerações/cirurgia , Aparelho Lacrimal/cirurgia , Masculino , Prognóstico , Estudos Retrospectivos , StentsRESUMO
Diabetic retinopathy (DR) is a serious diabetic complication caused by both environmental and genetic factors. Molecular mechanisms of DR may lead to the discovery of reliable prognostic indicators. The current study aimed to clarify the mechanism of microRNA-183 (miR-183) in DR in relation to the PI3K/Akt/VEGF signaling pathway. Microarray-based gene expression profiling of DR was used to identify the differentially expressed genes. Sprague-Dawley rats were used for the establishment of DR models, and then miR-183 was altered by mimic or inhibitor or BTG1 was downregulated by siRNA to explore the regulatory mechanism of miR-183 in DR. Furthermore, the expression of miR-183, CD34, endothelial nitric oxide synthase (eNOS), BTG1 and the PI3K/Akt/VEGF signaling pathway-related genes as well as reactive oxygen species (ROS) level was determined, and the relationship between miR-183 and BTG1 was also verified. Cell growth, cell apoptosis, and angiogenesis were determined. Microarray analysis revealed the involvement of miR-183 in DR via the PI3K/Akt/VEGF signaling pathway by targeting BTG1. Upregulated miR-183 and downregulated BTG1 were observed in retinal tissues of DR rats. miR-183 overexpression activated the PI3K/Akt/VEGF signaling pathway, upregulated CD34, eNOS, and ROS, and inhibited BTG1. BTG1 was confirmed as a target gene of miR-183. miR-183 overexpression or BTG1 knockdown promoted cell growth and tube formation while it suppressed cell apoptosis of vascular endothelial cells in DR rats. In this study, we demonstrated that miR-183 silencing inhibiting cell growth and tube formation in vascular endothelial cells of DR rats via the PI3K/Akt/VEGF signaling pathway by upregulating BTG1.
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Retinopatia Diabética/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Animais , Antígenos CD34/genética , Antígenos CD34/metabolismo , Retinopatia Diabética/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , MicroRNAs/metabolismo , Análise em Microsséries , Proteínas de Neoplasias/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
SIGNIFICANCE: Pregnancy-induced hypertension is a unique yet common complication in pregnant women and may cause retinopathy. Optical coherence tomography (OCT) may help find the features of retinopathy that are difficult to observe through fundus examination. Not all patients can fully recover from retinopathy. PURPOSE: This report describes a case of pregnancy-induced hypertension with retinopathy and represents the features of retinopathy in OCT and fundus fluorescein angiography. CASE REPORT: A 29-year-old pregnant woman presented with bilateral blurred vision and xanthopsia 2 days before her induced labor; she was also diagnosed as pre-eclamptic in the obstetrics department. The vision in her right eye was 20/33, and that in her left eye was 20/20. Fundus fluorescein angiography showed scattered-dot hypofluorescence around the disc at an early stage, and needle-like hyperfluorescence gradually appeared near the disc with late-stage fluorescein leakage in both eyes. Optical coherence tomography revealed multiple shallow retinal detachments with hyperreflective bright spots in the outer retina and clumped hyperreflective materials on the retinal pigment epithelium (RPE). CONCLUSIONS: Typical findings and some tiny changes in the outer retina and RPE can be observed through spectral-domain OCT. The clumped hyperreflective deposits in the outer retina may be by-products of RPE swelling and necrosis that lead to barrier dysfunctions and fluid leakage. These described features may help diagnose retinopathy from pregnancy-induced hypertension. Although it is a self-limited disease, the disruptions in the ellipsoid and interdigitation zones may not fully recover and result in reduced visual dysfunction. Therefore, control of hypertension is indicated.
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Hipertensão Induzida pela Gravidez/diagnóstico por imagem , Descolamento Retiniano/diagnóstico por imagem , Epitélio Pigmentado da Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Angiofluoresceinografia/métodos , Humanos , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Nifedipino/uso terapêutico , Gravidez , Descolamento Retiniano/tratamento farmacológico , Epitélio Pigmentado da Retina/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Acuidade Visual/fisiologiaRESUMO
Objective: To investigate whether echinacoside (ECH) protects the retina against ischemia/reperfusion (I/R) injury and the underlying mechanisms. Methods: Adult male Wistar rats were randomly divided into four groups: sham, shamâ plusâ ECH, I/Râ plusâ vehicle, and I/Râ plusâ ECH. Before the retinal I/R injury produced by high intraocular pressure (HOP), ECH was administered (20 mg/kg daily) for 7 days. The level of retinal cell damage was evaluated using Fluoro-Gold (FG) retrograde labeling and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) analysis 7 days after I/R. Optic nerve histology was analyzed with transmission electron microscopy. Levels of retinal malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. The expression of apoptosis-associated factors (Apaf-1, Parp, and Bad) were analyzed with western blotting and quantitative real-time PCR (qPCR). The production of proinflammatory cytokines (tumor necrosis factor-α [TNFα], interleukin-1 beta [IL-1ß], and IL-6) was analyzed with enzyme-linked immunosorbent assay (ELISA) 7 days after the I/R injury as well. Results: The administration of ECH not only preserved retinal morphology but also attenuated retinal inflammation and apoptosis at 7 days after the I/R injury and decreased I/R-induced oxidative stress in the retina statistically significantly. Conclusions: ECH protected against I/R-induced retinal injury, via activation of antioxidant enzymes and suppression of inflammation. Therefore, ECH could be a potential therapeutic candidate for the treatment and management of I/R retinal diseases.
Assuntos
Antioxidantes/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicosídeos/farmacologia , Nervo Óptico/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Retina/efeitos dos fármacos , Animais , Fator Apoptótico 1 Ativador de Proteases/genética , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Catalase/genética , Catalase/metabolismo , Modelos Animais de Doenças , Esquema de Medicação , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Masculino , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Nervo Óptico/metabolismo , Nervo Óptico/patologia , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Retina/metabolismo , Retina/patologia , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína de Morte Celular Associada a bcl/genética , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
BACKGROUND: Spectral domain optical coherence tomography (SD-OCT) is proposed as a way of predicting the development and likelihood of retinal astrocytic hamartoma (RAH) in tuberous sclerosis complex (TSC) in elderly patients. CASE PRESENTATION: This report describes a case of RAH in TSC in an elderly patient. The patient was a 62-year-old woman and experienced pain in the lower left abdomen for two years. Bilateral renal angiomyolipoma, multiple hepatic angiomyolipoma and multiple pulmonary nodules were demonstrated using computed tomography (CT). Brain CT showed bilateral multiple calcification near by the cella lateralis. A clinical diagnosis of TSC was made. Visual acuity (decimal) in the right and left eye was determined to be 0.6 and 0.8, respectively. SD-OCT revealed a retinal tumour in the inner layer of the retina in the right fundus and a pre-retinal membrane which may have evolved later. CONCLUSIONS: A routine ophthalmic examination is advised for patients suspected of having TSC to prevent this condition from being overlooked. In addition, an OCT examination can be used to predict the development and likelihood of RAH.
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Astrócitos/patologia , Hamartoma/etiologia , Doenças Retinianas/etiologia , Esclerose Tuberosa/complicações , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
PURPOSE: This study used optical coherence tomography scanning and 3D reconstruction of the macular region in high myopia to examine more thoroughly and carefully the differences between high myopia-related macular complications with and without dome-shape macula (DSM) and to determine whether the DSM's fine structure has an effect on them. METHODS: Retrospective analysis of the medical records of 345 eyes with high myopia who underwent an optical coherence tomography (OCT) examination. They were divided into the DSM group (69 eyes) and the group without DSM (276 eyes). Macular complications between the two groups were compared. The height of the DSM and the diameter of the dome base were measured. And then the association between DSM type, protrusion height and macular problems were analyzed. RESULTS: Epiretinal membrane (ERM) and extrafoveal schisis occurred more frequently in the DSM group, but the was no statistically significant difference in the frequency of foveal schisis between the two groups. The majority of eyes in the DSM categorization had a horizontal oval-shaped domain. In the DSM group, there was no evident difference in the percentage of eyes with macular complications in the groups below 150â um and above 150â um. CONCLUSIONS: OCT examination-based fine macular structure analysis reveals that DSM affects various macular problems in distinct ways. DSM could increase the risk of extrafoveal schisis and ERM while decreasing the risk of foveal schisis. The height of the DSM had no obvious impact on the prevalence of macular complications.
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Retinal ischemia plays a central role in several retinal diseases. The pathogenesis of retinal ischemia involves changes in gene expression. Valproic acid (VPA), a broad-spectrum histone deacetylase inhibitor, is an anticonvulsant and mood-stabilizing drug with neuroprotective effects. Here, we investigated whether VPA protects the retina and optic nerve axon from ischemic damage in a rat model and determined a possible protective mechanism. Adult male Wistar rats were randomized into sham, ischemia/reperfusion (I/R)-plus-vehicle, and I/R-plus-VPA groups. Rats received subcutaneous injections of 300 mg/kg VPA or phosphate-buffered saline twice a day after retinal ischemia induced by acute high intraocular pressure. Twenty-four hours after I/R, retinal neuron apoptosis was evaluated using the TUNEL assay. The expression of heat-shock protein 70 (Hsp70), activated-caspase-3, and apoptotic-protease-activating factor-1 (apaf-1), acetylation levels of histone H3, release of cytochrome c, and interaction between Hsp70 and apaf-1 were analyzed by immunoblotting analysis in all groups; the transcriptional activation of the Hsp70 gene and interaction between the Hsp70 promoter with p300 or HDAC1 were analyzed using chromatin immunoprecipitation assay. Seven days after I/R, the histological changes in the retina were evaluated using hematoxylin and eosin staining, and optic nerve axon damage was evaluated using toluidine blue staining and transmission electron microscopy. The density of retinal ganglion cells (RGCs) was analyzed using Fluoro-Gold retrograde labeling at 7, 14, 21 days after I/R. VPA markedly attenuated I/R-induced retinal neuron apoptosis, damage to RGCs, and morphological injury to the retina and optic nerve axons. VPA resulted in the upregulation of Hsp70 and hyperacetylation of histone H3, accompanied by Hsp70 promoter hyperacetylation, which may result from increased p300 recruitment to the Hsp70 promoter. Furthermore, VPA increased the binding between Hsp70 and apaf-1 to block apoptosome formation and reduced the release of cytochrome c and activation of caspase-3 in the retina after I/R. Therefore, VPA-mediated neuroprotection against I/R injury in the retina may involve cytoprotective Hsp70 induction via transcriptional activation and inhibition of the mitochondria-mediated apoptosis pathway.
Assuntos
Inibidores de Histona Desacetilases/farmacologia , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Doenças Retinianas/prevenção & controle , Células Ganglionares da Retina/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Ácido Valproico/farmacologia , Acetilação , Animais , Apoptose/efeitos dos fármacos , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Axônios/efeitos dos fármacos , Axônios/metabolismo , Axônios/patologia , Caspase 3/metabolismo , Citocromos c/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Histona Desacetilases/metabolismo , Histonas/metabolismo , Marcação In Situ das Extremidades Cortadas , Injeções Subcutâneas , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologiaRESUMO
Proliferative diabetic retinopathy, the primary cause of vision loss in adults, is one of serious microvascular complications caused by diabetes. Both poly-ADP-ribose-polymerase (PARP) and nuclear factor (NF)-κB signaling are involved in the injury process. Injury activates PARP, which in turn potentiates NF-κB activation and causes cell apoptosis. Like the NF-κB pathway, Notch1 signaling plays a key role in the regulation of cell proliferation, differentiation, and apoptosis. However, the connections between these signaling pathways are not well understood. In this study, we used both streptozotocin (STZ)-induced diabetic mice and human retinal vascular endothelial cells (HRVECs) cultured in high glucose to detect these relationships. We found that apoptosis was increased in both STZ-induced diabetic mice and high-glucose-treated HRVECs, which was due to increased activation of PARP, cleaved caspase3, and reduced expression of Notch1 and p-Akt. The results of Notch1 overexpression and knockdown indicated that Notch1 signaling participated in the interaction of PARP and p50, and inhibited PARP- and p50-mediated apoptosis directly. These phenomena could be blocked by pretreatment with the PI3K inhibitor wortmannin via reducing p-Akt levels. Thus, our study demonstrated that Notch1 signaling protects cells from PARP- and NF-κB-induced apoptosis under high glucose through the activation of Akt.
Assuntos
Apoptose/efeitos dos fármacos , Glucose/farmacologia , NF-kappa B/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Receptor Notch1/metabolismo , Retina/metabolismo , Androstadienos/farmacologia , Animais , Western Blotting , Caspase 3/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , NF-kappa B/genética , Subunidade p50 de NF-kappa B/genética , Subunidade p50 de NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Poli(ADP-Ribose) Polimerases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Receptor Notch1/genética , Retina/patologia , WortmaninaRESUMO
BACKGROUND: Posterior scleritis is a rare inflammatory ocular disease, characterized by severe and painful inflammation of the sclera. It is often misdiagnosed or underdiagnosed, due to its general and varying clinical presentation profile, which primarily involves pain and visual impairment but which can include eyelid edema, choroidal folds, serous retinal detachment, disc edema, hard exudates in fovea and subretinal mass. We report here a case of posterior scleritis, with symptoms of eye pain and red eye, initially misdiagnosed as acute conjunctivitis. CASE SUMMARY: A 56-year-old man presented to a local hospital with complaint of pain and redness in the right eye. The initial diagnosis was acute conjunctivitis and he was given antibiotic eyedrops. Upon week-long continuance of the symptoms despite treatment, he presented to our hospital. Initial examination revealed a shallow anterior chamber in the right eye and vision reduction to 0.6. Further testing by optical coherence tomography, ultrasound biomicroscopy, and fundus photography indicated diagnosis of posterior scleritis. The patient was given methylprednisolone (oral) on a tapered reduction schedule (starting with 70 mg/d). According to the peaks and troughs of symptoms, compound betamethasone injection was administered into the bulb, culminating in discontinuation of the oral corticosteroid. Subsequent optical coherence tomography showed the subretinal fluid near the optic disc to be completely absorbed after treatment. CONCLUSION: Posterior scleritis should be among the differential diagnosis of eye pain and redness, and diagnosis requires further ophthalmic accessory examination, such as by optical coherence tomography.
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Fungal keratitis is a relatively common ocular disease requiring positive medical management combined with surgical intervention. Interleukin-17 (IL-17) was reported to promote the activation and mobilization of neutrophile granulocyte to foci of inflammation. This study investigated the effect of IL-17 production from Th17 cells on the progression of fungal keratitis. A mouse model of fungal keratitis induced by Candida albicans was successfully constructed to detect infiltration of inflammatory cells in corneal tissues by hematoxylin-eosin (HE) staining and immunohistochemistry. Fungal load capacity of mouse cornea was also detected. The regulatory role of IL-17 in fungal keratitis with the involvement of CX43 was investigated with the relevant expression of inflammatory factors detected and activation of vascular endothelial cells assessed. Furthermore, in vivo experiment was also performed to confirm the role of CX43 in keratitis. Mice with fungal keratitis showed increased level of inflammatory cytokines and infiltration of inflammatory cells. Silencing IL-17 in Th17 cells and overexpressing CX43 could inhibit the activation of vascular endothelial cells. Besides, CX43 knockdown in vivo alleviated fungal keratitis in mice. The possible mechanism of the above findings could be IL-17 inhibiting the level of CX43 through the AKT signaling pathway. Taken together, IL-17 could inhibit the occurrence and development of fungal keratitis by suppressing CX43 expression through the AKT signaling pathway. Therefore, this study provides a potential target for the treatment of fungal keratitis.
Assuntos
Candidíase/metabolismo , Conexina 43/metabolismo , Endotélio Vascular/metabolismo , Infecções Oculares Fúngicas/metabolismo , Interleucina-17/biossíntese , Ceratite/metabolismo , Células Th17/imunologia , Animais , Candida albicans , Candidíase/imunologia , Candidíase/patologia , Células Cultivadas , Conexina 43/antagonistas & inibidores , Conexina 43/genética , Córnea/irrigação sanguínea , Córnea/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Infecções Oculares Fúngicas/imunologia , Infecções Oculares Fúngicas/patologia , Feminino , Interleucina-17/genética , Ceratite/imunologia , Ceratite/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
PURPOSES: To investigate whether valproic acid (VPA) has a neuroprotective effect against ischemia/reperfusion (I/R) injury in the rat retina, and to elucidate the potential antioxidant mechanisms involved. METHODS: Adult male Wistar rats were randomly divided into four groups: sham (group A), sham plus VPA (group B), I/R plus vehicle (group C), and I/R plus VPA (group D). Retinal I/R injury was produced by inducing an exceedingly high intraocular pressure (IOP). Prior to insult, VPA was administered subcutaneously (300 mg/kg twice daily) for 7 days, after which the animal was sacrificed. Levels of retinal malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. Protein expressions of retinal poly(ADP-ribose) (PAR) and nitrotyrosine (NT) were analyzed by Western blotting 24 h after injury. Apoptosis of retinal cells was evaluated 24 h after I/R injury by immunofluorescence of activated caspase-3 in histological sections of retina. Seven days after reperfusion, electroretinography (ERG) was performed, and retinal histological changes were examined by light microscopy. RESULTS: Following ischemia, the thickness of the entire retina, including the inner nuclear layer (INL) and inner plexiform layer (IPL), as well as the number of cells in the ganglion cell layer (GCL) were significantly greater in group D than in group C (p < 0.05). VPA suppressed I/R-induced reductions in ERG a- and b-wave amplitudes (p < 0.05). VPA attenuated I/R-induced activation of caspase-3 in ganglion cells and INL cells (p < 0.001). VPA significantly decreased MDA levels and increased activities of SOD, GSH-Px, and CAT in group D (p < 0.05). VPA attenuated activation of PAR and accumulation of NT in the retina after I/R (p < 0.01). CONCLUSIONS: VPA protects the retina from I/R injury by enhancing anti-oxidative effects and inhibiting apoptosis of retinal cells.