RESUMEN
Lycium ruthenicum Murray (LR) is a medicine and edible plant in Northwest China, and L. ruthenicum Murray anthocyanins (LRA) are green antioxidants with various pharmacological activities, such as antioxidant and anti-inflammatory activities. However, the protective effect and mechanism of LRA against retinal damage induced by blue light exposure are poorly understood. This study explored the protective effects and potential mechanisms of LRA on retinal damage induced by blue light exposure in vitro and in vivo. The results showed that LRA could ameliorate oxidative stress injury by activating the antioxidant stress nuclear factor-related factor 2 pathway, promoting the expression of phase II detoxification enzymes (HO-1, NQO1) and endogenous antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), and reducing reactive oxygen species and malondialdehyde levels. Additionally, LRA could inhibit inflammatory response by decreasing the expression of blue light exposure-induced nuclear factor-κB (NF-κB) pathway-related proteins (NF-κB and p-IκBα), as well as interleukin (IL)-6, tumor necrosis factor-α, IL-1ß pro-inflammatory factors and pro-inflammatory chemokine VEGF, and increasing the expression of anti-inflammatory factor IL-10. Furthermore, LRA could ameliorate oxidative stress-induced apoptosis by upregulating Bcl-2 and downregulating Bax and Caspase-3 protein expression. All these results indicate that LRA can be used as an antioxidant dietary supplement for the treatment or prevention of retinal diseases.
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Antocianinas , Antioxidantes , Apoptosis , Luz , Lycium , Estrés Oxidativo , Retina , Lycium/química , Animales , Antocianinas/farmacología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/efectos de la radiación , Retina/efectos de la radiación , Retina/efectos de los fármacos , Retina/metabolismo , Luz/efectos adversos , Antioxidantes/farmacología , Ratones , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Masculino , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo , Sustancias Protectoras/farmacología , Malondialdehído/metabolismo , Antiinflamatorios/farmacología , Superóxido Dismutasa/metabolismo , Enfermedades de la Retina/prevención & control , Enfermedades de la Retina/etiología , Luz AzulRESUMEN
Activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway protects against N-methyl-D-aspartic acid (NMDA)-induced excitotoxic retinal injury. AMPK activation enhances fatty acid metabolism and ketone body synthesis. Ketone bodies are transported into neurons by monocarboxylate transporters (MCTs) and exert neuroprotective effects. In this study, we examined the distribution and expression levels of MCT1 and MCT2 in the retina and analyzed the effects of pharmacological inhibition of MCTs on the protective effects of metformin and 5-aminoimidazole-4-carboxamide (AICAR), activators of AMPK, against NMDA-induced retinal injury in rats. MCT1 was expressed in the blood vessels, processes of astrocytes and Müller cells, and inner segments of photoreceptors in the rat retina, whereas MCT2 was expressed in neuronal cells in the ganglion cell layer (GCL) and in astrocyte processes. The expression levels of MCT2, but not MCT1, decreased one day after intravitreal injection of NMDA (200 nmol). Intravitreal injection of NMDA decreased the number of cells in the GCL compared to the vehicle seven days after injection. Simultaneous injection of metformin (20 nmol) or AICAR (50 nmol) with NMDA attenuated NMDA-induced cell loss in the GCL, and these protective effects were attenuated by AR-C155858 (1 pmol), an inhibitor of MCTs. AR-C155858 alone had no significant effect on the retinal structure. These results suggest that AMPK-activating compounds protect against NMDA-induced excitotoxic retinal injury via mechanisms involving MCTs in rats. NMDA-induced neurotoxicity may be associated with retinal neurodegenerative changes in glaucoma and diabetic retinopathy. Therefore, AMPK-activating compounds may be effective in managing these retinal diseases.
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Metformina , Enfermedades de la Retina , Tiofenos , Uracilo/análogos & derivados , Ratas , Animales , Proteínas Quinasas Activadas por AMP/metabolismo , N-Metilaspartato/toxicidad , Ratas Sprague-Dawley , Retina/metabolismo , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/prevención & control , Enfermedades de la Retina/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Metformina/efectos adversosRESUMEN
PURPOSE OF REVIEW: To review the literature evaluating systemic medications for treatment of sickle cell disease (SCD) and their applications for sickle cell retinopathy. RECENT FINDINGS: Prior studies have demonstrated the efficacy of traditional systemic therapies in reducing the risk of development of sickle cell retinopathy. Since 2017, several new and promising disease-modifying therapies for sickle cell disease have been approved for clinical use, including the first genetic therapies such as exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel). These treatments have shown promising results for systemic management but are not widely utilized due to limited access and high cost. The efficacy of these therapies for the prevention of sickle cell retinopathy remains unknown and opens the door to new avenues for research. Furthermore, the role of systemic therapy for the management of hemoglobin SC (HbSC) disease, which has milder systemic effects but higher likelihood of causing retinopathy, remains poorly understood. SUMMARY: Hydroxyurea has been a mainstay of systemic management of SCD with prior work suggesting its ability to reduce the likelihood of developing retinopathy. There are several new and potentially curative systemic therapies for SCD, though their role in retinopathy prevention and management has not been studied extensively. Future studies are necessary to understand the implications of these emerging therapies for sickle cell retinopathy.
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Anemia de Células Falciformes , Enfermedad de la Hemoglobina SC , Enfermedades de la Retina , Humanos , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/genética , Enfermedad de la Hemoglobina SC/complicaciones , Enfermedad de la Hemoglobina SC/tratamiento farmacológico , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/prevención & control , Hidroxiurea/uso terapéuticoRESUMEN
Amyloid-beta (Aß), a family of aggregation-prone and neurotoxic peptides, has been implicated in the pathophysiology of age-related macular degeneration (AMD). We have previously shown that oligomeric and fibrillar species of Aß42 exerted retinal toxicity in rats, but while the consequences of exposure to amyloid were related to intracellular effects, the mechanism of Aß42 internalization in the retina is not well characterized. In the brain, the 67 kDa laminin receptor (67LR) participates in Aß-related neuronal cell death. A short peptide derived from pigment epithelium-derived factor (PEDF), formerly designated PEDF-335, was found to mitigate experimental models of ischemic retinopathy via targeting of 67LR. In the present study, we hypothesized that 67LR mediates the uptake of pathogenic Aß42 assemblies in the retina, and that targeting of this receptor by PEDF-335 may limit the internalization of Aß, thereby ameliorating its retinotoxicity. To test this assumption ARPE-19 cells in culture were incubated with PEDF-335 before treatment with fibrillar or oligomeric structures of Aß42. Immunostaining confirmed that PEDF-335 treatment substantially prevented amyloid internalization into ARPE-19 cells and maintained their viability in the presence of toxic oligomeric and fibrillar Aß42 entities in vitro. FRET competition assay was performed and confirmed the binding of PEDF-335 to 67LR in RPE-like cells. Wild-type rats were treated with intravitreal PEDF-335 in the experimental eye 2 days prior to administration of retinotoxic Aß42 oligomers or fibrils to both eyes. Retinal function was assessed by electroretinography through 6 weeks post injection. The ERG responses in rats treated with oligomeric or fibrillar Aß42 assemblies were near-normal in eyes previously treated with intravitreal PEDF-335, whereas those measured in the control eyes treated with injection of the Aß42 assemblies alone showed pathologic attenuation of the retinal function through 6 weeks. The retinal presence of 67LR was determined ex vivo by immunostaining and western blotting. Retinal staining demonstrated the constitutional expression of 67LR mainly in the retinal nuclear layers. In the presence of Aß42, the levels of 67LR were increased, although its retinal distribution remained largely unaltered. In contrast, no apparent differences in the retinal expression level of 67LR were noted following exposure to PEDF-335 alone, and its pattern of localization in the retina remained similarly concentrated primarily in the inner and outer nuclear layers. In summary, we found that PEDF-335 confers protection against Aß42-mediated retinal toxicity, with significant effects noted in cells as well as in vivo in rats. The effects of PEDF-335 in the retina are potentially mediated via binding to 67LR and by at least partial inhibition of Aß42 internalization. These results suggest that PEDF-335 may merit further consideration in the development of targeted inhibition of amyloid-related toxicity in the retina. More broadly, our observations provide evidence on the importance of extracellular versus intracellular Aß42 in the retina and suggest concepts on the molecular mechanism of Aß retinal pathogenicity.
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Péptidos beta-Amiloides , Electrorretinografía , Proteínas del Ojo , Factores de Crecimiento Nervioso , Serpinas , Animales , Serpinas/metabolismo , Proteínas del Ojo/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Ratas , Péptidos beta-Amiloides/toxicidad , Péptidos beta-Amiloides/metabolismo , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Fragmentos de Péptidos/toxicidad , Modelos Animales de Enfermedad , Receptores de Laminina/metabolismo , Masculino , Retina/efectos de los fármacos , Retina/metabolismo , Humanos , Inyecciones Intravítreas , Western Blotting , Enfermedades de la Retina/prevención & control , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/inducido químicamente , Células CultivadasRESUMEN
Retinal ischemia is a significant factor in various vision-threatening diseases, but effective treatments are currently lacking. This study explores the potential of stem cell factor (SCF) in regulating the neurovascular unit as a therapeutic intervention for retinal ischemic diseases. A chronic retinal ischemia model was established in Brown Norway rats using bilateral common carotid artery occlusion (BCCAO). Subsequent SCF treatment resulted in a remarkable recovery of retinal function, as indicated by electroretinogram, light/dark transition test, and optokinetic head tracking test results. Histological examination demonstrated a significant increase in the number of retinal neurons and an overall thickening of the retina. Immunofluorescence confirmed these findings and further demonstrated that SCF treatment regulated retinal remodeling. Notably, SCF treatment ameliorated the disrupted expression of synaptic markers in the control group's BCCAO rats and suppressed the activation of Müller cells and microglia. Retinal whole-mount analysis revealed a significant improvement in the abnormalities in retinal vasculature following SCF treatment. Transcriptome sequencing analysis revealed that SCF-induced transcriptome changes were closely linked to the Wnt7 pathway. Key members of the Wnt7 pathway, exhibited significant upregulation following SCF treatment. These results underscore the protective role of SCF in the neurovascular unit of retinal ischemia rats by modulating the Wnt7 pathway. SCF administration emerges as a promising therapeutic strategy for retinal ischemia-related diseases, offering potential avenues for future clinical interventions.
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Arteriopatías Oclusivas , Enfermedades de las Arterias Carótidas , Enfermedades de la Retina , Ratas , Animales , Factor de Células Madre , Isquemia/metabolismo , Enfermedades de la Retina/prevención & control , Enfermedades de la Retina/patología , Retina , Vasos Retinianos/metabolismo , Arteriopatías Oclusivas/patologíaRESUMEN
INTRODUCTION: The objective of this study was to investigate the impact of N-acetylserotonin (NAS) on the autophagy of retinal cells in rats with retinal ischemia-reperfusion injury (RIRI) and to explore the mechanisms by which NAS administration can alleviate RIRI through the tropomyosin-related kinase receptor B (TrkB)/protein kinase B (Akt)/nuclear factor erythroid-derived factor 2-related factor (Nrf2) signaling pathway. METHODS: Healthy adult male rats were randomly assigned to four groups: sham, RIRI, RIRI+NAS, and RIRI+NAS+ANA-12. The RIRI group was induced by elevating intraocular pressure, and changes in retinal structure and edema were assessed using H&E staining. The RIRI+NAS and RIRI+NAS+ANA-12 groups received intraperitoneal injections of NAS before and after modeling. The RIRI+NAS+ANA-12 group was also administered ANA-12, a TrkB antagonist. Immunohistochemical staining and Western blot analysis were used to evaluate phosphorylated TrkB (p-TrkB), phosphorylated Akt (p-Akt), Nrf2, sequestosome 1 (P62), and microtubule-associated protein 1 light chain 3 (LC3-II) levels in the retinas of each group. Electroretinogram was recorded to detect retinal function in each group of rats 24 h after modeling. RESULTS: The RIRI+NAS group had a thinner retina and more retinal ganglion cells (RGCs) than RIRI and RIRI+NAS+ANA-12 groups (p < 0.05). Immunohistochemical staining and Western blot results showed that p-TrkB, p-Akt, n-Nrf2, and P62 levels in the RIRI+NAS group were higher compared with those in RIRI and RIRI+NAS+ANA-12 groups (p < 0.05). Also, lower LC3-II levels were observed in the RIRI+NAS group compared with that in RIRI and RIRI+NAS+ANA-12 groups (p < 0.05). Electroretinogram recording results showed that 24 h after retinal ischemia-reperfusion, the magnitude of b-wave changes was attenuated in the RIRI+NAS group compared with the RIRI group (p < 0.05). CONCLUSION: The administration of NAS activates the TrkB/Akt/Nrf2 signaling pathway, reduces autophagy, alleviates retinal edema, promotes the survival of retinal ganglion cells (RGCs), and provides neuroprotection against retinal injury.
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Daño por Reperfusión , Enfermedades de la Retina , Serotonina/análogos & derivados , Ratas , Masculino , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Retina/metabolismo , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/prevención & control , Transducción de Señal , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismoRESUMEN
Purpose: This study aimed to explore the impact of GSK840 on retinal neuronal injury after retinal ischemia/reperfusion (IR) and its associated mechanism. Methods: We established an in vivo mouse model of IR and an in vitro model of oxygen and glucose deprivation/reoxygenation (OGDR) in primary mouse retinal ganglion cells (RGCs). GSK840, a small-molecule compound, was used to specifically inhibit RIPK3/MLKL-dependent necroptosis. Retinal structure and function evaluation was performed by using hematoxylin and eosin staining, optical coherence tomography, and electroretinography. Propidium Iodide (PI) staining was used for detection of necroptotic cell death, whereas Western blot analysis and immunofluorescence were used to assess necroptosis-related proteins and inner retinal neurons. Results: RIPK3/MLKL-dependent necroptosis was rapidly activated in RGCs following retinal IR or OGDR. GSK840 helped maintain relatively normal inner retinal structure and thickness by preserving inner retinal neurons, particularly RGCs. Meanwhile, GSK840 ameliorated IR-induced visual dysfunction, as evidenced by the improved amplitudes of photopic negative response, a-wave, b-wave, and oscillatory potentials. And GSK840 treatment significantly reduced the population of PI+ RGCs after injury. Mechanistically, GSK840 ameliorated RGC necroptosis by inhibiting the RIPK3/MLKL pathway. Conclusions: GSK840 exerts protective effects against retinal neuronal injury after IR by inhibiting RIPK3/MLKL-mediated RGC necroptosis. GSK840 may represent a protective strategy for RGC degeneration in ischemic retinopathy.
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Lesiones Oculares , Enfermedades de la Retina , Animales , Ratones , Necroptosis , Enfermedades de la Retina/etiología , Enfermedades de la Retina/prevención & control , Células Ganglionares de la Retina , Glucosa , Isquemia , Oxígeno , Proteínas QuinasasRESUMEN
Purpose: Retinal ischemia is a common cause of a variety of eye diseases, such as retinopathy of prematurity, diabetic retinopathy, and vein occlusion. Protein kinase RNA-activated-like endoplasmic reticulum (ER) kinase (PERK), one of the main ER stress sensor proteins, has been involved in many diseases. In this study, we investigated the role of PERK in ischemia-induced retinopathy using a mouse model of oxygen-induced retinopathy (OIR). Methods: OIR was induced by subjecting neonatal pups to 70% oxygen at postnatal day 7 (P7) followed by returning to room air at P12. GSK2606414, a selective PERK inhibitor, was orally administrated to pups right after they were returned to room air once daily until 1 day before sample collection. Western blot, immunostaining, and quantitative PCR were used to assess PERK phosphorylation, retinal changes, and signaling pathways in relation to PERK inhibition. Results: PERK phosphorylation was prominently increased in OIR retinas, which was inhibited by GSK2606414. Concomitantly, PERK inhibition significantly reduced retinal neovascularization (NV) and retinal ganglion cell (RGC) loss, restored astrocyte network, and promoted revascularization. Furthermore, PERK inhibition downregulated the recruitment/proliferation of mononuclear phagocytes but did not affect OIR-upregulated canonical angiogenic pathways. Conclusions: Our results demonstrate that PERK is involved in ischemia-induced retinopathy and its inhibition using GSK2606414 could offer an effective therapeutic intervention aimed at alleviating retinal NV while preventing neuron loss during retinal ischemia.
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Enfermedades de la Retina , Neovascularización Retiniana , Retinopatía de la Prematuridad , eIF-2 Quinasa , Animales , Ratones , Animales Recién Nacidos , Modelos Animales de Enfermedad , Isquemia/metabolismo , Ratones Endogámicos C57BL , Neovascularización Patológica/metabolismo , Oxígeno/metabolismo , Retina , Enfermedades de la Retina/etiología , Enfermedades de la Retina/prevención & control , Células Ganglionares de la Retina/metabolismo , Neovascularización Retiniana/prevención & control , Neovascularización Retiniana/metabolismo , Retinopatía de la Prematuridad/metabolismo , eIF-2 Quinasa/metabolismoRESUMEN
PURPOSE: To investigate the possible beneficial effects of omega-3 polyunsaturated fatty acids (ω3-PUFAs) in ischemic retinal angiogenesis and whether AMP-activated protein kinase (AMPK) is involved. METHODS: Human retinal microvascular endothelial cells (hRMECs) were exposed to dimethyloxalylglycine (DMOG), a hypoxia-inducible factor hydroxylase inhibitor, in the presence or absence of docosahexaenoic acid (DHA) and small interfering RNA (siRNA) for AMPKα for 24 h. Ischemic factors, endothelial mesenchymal transition marker, endothelial barrier integrity, cell migration, and tube formation were evaluated. Neonatal AMPKα2-/- and control wild-type (WT) mice were submitted to an oxygen-induced retinopathy (OIR) protocol; their nursing mother mice were either fed ω3-PUFAs or not. In the end, ischemic markers and endothelial cell proliferation were evaluated in neonatal mouse retinal tissue through immunohistochemical or immunofluorescent assays among all studied groups. RESULTS: Cells exposed to DMOG displayed increased expressions of hypoxic and endothelial mesenchymal transition (vimentin) markers and barrier disarrangement of Zonula Occludens-1 compared to the control, accompanied by increased cellular migration and tube formation (p < 0.05). AMPK activity was significantly decreased. Supplementation with DHA restored the mentioned alterations compared to DMOG (p<0.05). In siRNAAMPKα-treated cells, the beneficial effects observed with DHA were abolished. DHA upregulated G-protein receptor-120 (GPR120), which promptly increased intracellular levels of calcium (p ≤ 0.001), which consequently increased Calcium/calmodulin-dependent protein kinase kinase ß expression (CaMKKß) thus phosphorylating AMPKThr172. AMPKα2-/- and wild-type (WT) OIR mice exhibited similar retinal ischemic changes, and the oral supplementation with ω3-PUFA efficiently prevented the noticed ischemic alterations only in WT mice, suggesting that AMPKα2 is pivotal in the protective effects of ω3-PUFA. CONCLUSIONS: ω3-PUFAs protect the retina from the effects of ischemic conditions, and this effect occurs via the GPR120-CaMKKß-AMPK axis. A better understanding of this mechanism might improve the control of pathological angiogenesis in retinal ischemic diseases.
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Proteínas Quinasas Activadas por AMP , Ácidos Grasos Omega-3 , Isquemia , Enfermedades de la Retina , Animales , Humanos , Ratones , Adenilato Quinasa/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Calcio/metabolismo , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina , Ácidos Docosahexaenoicos/farmacología , Células Endoteliales/metabolismo , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Isquemia/prevención & control , Ratones Endogámicos C57BL , Retina/metabolismo , Enfermedades de la Retina/prevención & control , ARN Interferente Pequeño/farmacologíaRESUMEN
Radiation retinopathy is an occlusive vascular pathology following radiotherapy, generally targeted on the eye or peri-ocular structures. Despite increasingly precise techniques (stereotactic radiosurgery, proton therapy, etc.), the inclusion of the retina in the radiation field is sometimes unavoidable. This can lead to a severe pathology, which can ultimately cause blindness or even the anatomical loss of the eye when neovascular glaucoma occurs, due to the abnormal proliferation of neovessels. Radiation retinopathy have been described for more than a century, but it has recently seen great advances in both diagnosis and treatment. The advances of efficient and less invasive examinations in our clinical practice, such as OCT-angiography, allows for easier screening and diagnosis at earlier stages. Thus a new approach to the pathology is necessary, first of all through new definitions and classifications including previously undetected minimal forms. Furthermore, the recent appearance of intravitreal therapies by injection of anti-VEGF or dexamethasone implants has drastically changed the visual prognosis of these patients, who were previously treated only by retinal photocoagulation of the ischaemic areas. Recent studies have even shown the effectiveness of these new molecules in preventing the development of radiation retinopathy. This review of the literature provides an update on this disease and details how these recent diagnostic and therapeutic developments may play a role in the management of this complication.
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Traumatismos por Radiación , Radiocirugia , Enfermedades de la Retina , Humanos , Enfermedades de la Retina/etiología , Enfermedades de la Retina/prevención & control , Traumatismos por Radiación/diagnóstico , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Inhibidores de la Angiogénesis/uso terapéutico , Ojo , Radiocirugia/efectos adversosRESUMEN
Purpose: Pituitary adenylate cyclase-activating polypeptide (PACAP) has shown potent neuroprotective effects in central nervous system and retina disorders. However, whether PACAP can attenuate retinal neurodegeneration induced by acute ocular hypertension (AOH) and the underlying mechanisms remain unknown. In this study, we aimed to investigate the effects of PACAP on the survival and function of retinal ganglion cells (RGCs), apoptosis, and inflammation in a mouse model of AOH injury. Methods: PACAP was injected into the vitreous body immediately after inducing AOH injury. Hematoxylin and eosin staining and optical coherence tomography were used to evaluate the loss of retina tissue. Pattern electroretinogram was used to evaluate the function of RGCs. TUNEL assay was used to detect apoptosis. Immunofluorescence and western blot were employed to evaluate protein expression levels. Results: PACAP treatment significantly reduced the losses of whole retina and inner retina thicknesses, Tuj1-positive RGCs, and the amplitudes of pattern electroretinograms induced by AOH injury. Additionally, PACAP treatment remarkably reduced the number of TUNEL-positive cells and inhibited the upregulation of Bim, Bax, and cleaved caspase-3 and downregulation of Bcl-xL after AOH injury. Moreover, PACAP markedly inhibited retinal reactive gliosis and vascular inflammation, as demonstrated by the downregulation of GFAP, Iba1, CD68, and CD45 in PACAP-treated mice. Furthermore, upregulated expression of NF-κB and phosphorylated NF-κB induced by AOH injury was attenuated by PACAP treatment. Conclusions: PACAP could prevent the loss of retinal tissue and improve the survival and function of RGCs. The neuroprotective effect of PACAP is probably associated with its potent anti-apoptotic and anti-inflammatory effects.
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Lesiones Oculares , Glaucoma , Fármacos Neuroprotectores , Hipertensión Ocular , Enfermedades de la Retina , Animales , Antiinflamatorios/uso terapéutico , Lesiones Oculares/tratamiento farmacológico , Glaucoma/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Inyecciones Intravítreas , Ratones , FN-kappa B , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/farmacología , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/etiología , Enfermedades de la Retina/prevención & controlRESUMEN
PURPOSE: Retinal and optic nerve damage in glaucoma involves excitotoxicity via N-methyl-D-aspartate (NMDA) receptors. Since, trans-resveratrol (TR) is known to provide neuroprotection, we investigated its protective effects against NMDA-induced retinal and optic nerve injury. METHODS: Sprague Dawley rats were divided into four groups which received vehicle (PBS), NMDA, and TR 0.4 or TR 4 nmol 24 h prior to NMDA, unilaterally and intravitreally. Seven days post-injection, rats were euthanized; eyeballs were enucleated and subjected to hematoxylin and eosin and terminal transferase dUTP nick end labeling staining while optic nerves were isolated for toluidine blue staining. RESULTS: Retinal morphometry showed that ganglion cell layer (GCL) layer thickness within inner retina (IR), retinal cell count (RCC) per 100-µm length of GCL, RCC per 100-µm2 area of GCL, and RCC per 100 µm2 of IR were significantly higher in both TR-treated groups compared to the NMDA group. No differences were observed between the two dose groups. Optic nerve morphology was in accordance with the retinal morphology whereby TR-treated groups showed significantly lesser degenerative changes compared to NMDA-treated group. CONCLUSIONS: TR protects against NMDA-induced changes in retinal and optic nerve morphology by preventing retinal cell apoptosis.
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Carcinoma de Células Renales , Lesiones Oculares , Neoplasias Renales , Traumatismos del Nervio Óptico , Enfermedades de la Retina , Animales , Apoptosis , N-Metilaspartato/toxicidad , Nervio Óptico , Traumatismos del Nervio Óptico/inducido químicamente , Traumatismos del Nervio Óptico/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Resveratrol/farmacología , Retina , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/prevención & controlRESUMEN
We rely on vision more than on any other sense to obtain information about our environment. Hence, the loss or even impairment of vision profoundly affects our quality of life. Diet or food components have already demonstrated beneficial effects on the development of retinal diseases. Recently, there has been a growing interest in resources from marine animals and plants for the prevention of retinal diseases through nutrition. Especially fish intake and omega-3 fatty acids have already led to promising results, including associations with a reduced incidence of retinal diseases. However, the underlying molecular mechanisms are insufficiently explained. The aim of this review was to summarize the known mechanistic effects of marine resources on the pathophysiological processes in retinal diseases. We performed a systematic literature review following the PRISMA guidelines and identified 107 studies investigating marine resources in the context of retinal diseases. Of these, 46 studies described the underlying mechanisms including anti-inflammatory, antioxidant, antiangiogenic/vasoprotective, cytoprotective, metabolic, and retinal function effects, which we critically summarize. We further discuss perspectives on the use of marine resources for human nutrition to prevent retinal diseases with a particular focus on regulatory aspects, health claims, safety, and bioavailability.
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Ácidos Grasos Omega-3 , Enfermedades de la Retina , Animales , Antioxidantes/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Humanos , Calidad de Vida , Retina/metabolismo , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/prevención & controlRESUMEN
Chronic oxidative stress eventually leads to protein aggregation in combination with impaired autophagy, which has been observed in age-related macular degeneration. We have previously shown an effective age-related macular degeneration disease model in mice with nuclear factor-erythroid 2-related factor-2 (NFE2L2) knockout. We have also shown pinosylvin, a polyphenol abundant in bark waste, to increase human retinal pigment epithelium cell viability in vitro. In this work, the effects of commercial natural pinosylvin extract, Retinari™, were studied on the electroretinogram, optical coherence tomogram, autophagic activity, antioxidant capacity, and inflammation markers. Wild-type and NFE2L2 knockout mice were raised until the age of 14.8 ± 3.8 months. They were fed with either regular or Retinari™ chow (141 ± 17.0 mg/kg/day of pinosylvin) for 10 weeks before the assays. Retinari™ treatment preserved significant retinal function with significantly preserved a- and b-wave amplitudes in the electroretinogram responses. Additionally, the treatment prevented thinning of the retina in the NFE2L2 knockout mice. The NFE2L2 knockout mice showed reduced ubiquitin-tagged protein accumulation in addition to local upregulation of complement factor H and antioxidant enzymes superoxide dismutase 1 and catalase. Therefore, the treatment in the NFE2L2 KO disease model led to reduced chronic oxidative stress and sustained retinal function and morphology. Our results demonstrate that pinosylvin supplementation could potentially lower the risk of age-related macular degeneration onset and slow down its progression.
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Antioxidantes/farmacología , Factor 2 Relacionado con NF-E2/fisiología , Estrés Oxidativo , Extractos Vegetales/farmacología , Enfermedades de la Retina/prevención & control , Estilbenos/farmacología , Animales , Apoptosis , Proliferación Celular , Células Cultivadas , Ratones , Ratones Noqueados , Enfermedades de la Retina/etiología , Enfermedades de la Retina/metabolismo , Enfermedades de la Retina/patologíaRESUMEN
The novel pandemic coronavirus disease 2019 (COVID-19) leading to health and economic problems worldwide is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 mainly occurs as a lower respiratory tract infection, there is multiorgan involvement in infected patients. The disease is transmitted from person to person through air droplets or contact with contaminated surfaces. SARS-CoV-2 leads to this systemic involvement by attaching to angiotensin-converting enzyme 2 (ACE2) receptors located on several human cells. Since SARS-CoV-2 RNA has been found in tears of infected patients, ocular surface may allow the virus to transmit to nasopharynx via the nasolacrimal duct. This narrative review aims to sum up all segmental ocular complications, ocular adverse effects of COVID-19 treatment, and preventive measures suggested to minimize the SARS-CoV-2 transmission between patients and ophthalmologists by reviewing currently available literature.
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COVID-19/diagnóstico , Infecciones Virales del Ojo/diagnóstico , SARS-CoV-2 , Lágrimas/virología , COVID-19/prevención & control , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19 , Conjuntivitis Viral/diagnóstico , Conjuntivitis Viral/prevención & control , Conjuntivitis Viral/virología , Encefalitis Viral/diagnóstico , Encefalitis Viral/prevención & control , Encefalitis Viral/virología , Infecciones Virales del Ojo/prevención & control , Infecciones Virales del Ojo/virología , Humanos , Medicina Preventiva/métodos , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/prevención & control , Enfermedades de la Retina/virología , SARS-CoV-2/patogenicidadRESUMEN
Cardiovascular diseases lead to retinal ischemia, one of the leading causes of blindness. Retinal ischemia triggers pathological retinal glial responses and functional deficits. Therefore, maintaining retinal neuronal activities and modulating pathological gliosis may prevent loss of vision. Previously, pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was nominated as a promising drug in retinal ischemia. However, a protective role of pemafibrate remains untouched in cardiovascular diseases-mediated retinal ischemia. Therefore, we aimed to unravel systemic and retinal alterations by treating pemafibrate in a new murine model of retinal ischemia caused by cardiovascular diseases. Adult C57BL/6 mice were orally administered pemafibrate (0.5 mg/kg) for 4 days, followed by unilateral common carotid artery occlusion (UCCAO). After UCCAO, pemafibrate was continuously supplied to mice until the end of experiments. Retinal function (a-and b-waves and the oscillatory potentials) was measured using electroretinography on day 5 and 12 after UCCAO. Moreover, the retina, liver, and serum were subjected to qPCR, immunohistochemistry, or ELISA analysis. We found that pemafibrate enhanced liver function, elevated serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the eye, and protected against UCCAO-induced retinal dysfunction, observed with modulation of retinal gliosis and preservation of oscillatory potentials. Our current data suggest a promising pemafibrate therapy for the suppression of retinal dysfunction in cardiovascular diseases.
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Arteriopatías Oclusivas/complicaciones , Benzoxazoles/farmacología , Butiratos/farmacología , Arteria Carótida Común/fisiopatología , Enfermedades de la Retina/prevención & control , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedades de la Retina/etiología , Enfermedades de la Retina/patologíaRESUMEN
Purpose: Retinopathies are associated with the injury of retinal microvascular endothelial cells. Salidroside (SAL) is a medicinal supplement that has antioxidative and cytoprotective properties. We hypothesized that SAL might have a protective function in retinopathies. This research aims to explore the function and mechanism of SAL in hypoxia-induced retinal microvascular endothelial cell injury. Methods: Human retinal microvascular endothelial cells (HRMECs) injury was induced by culturing under hypoxic condition. The function of SAL on HRMECs injury was investigated using cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, Western blotting, and enzyme linked immunosorbent assay. MicroRNA (miR)-138, roundabout 4 (ROBO4), and proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways were examined using quantitative reverse transcription polymerase chain reaction or Western blotting. The target correlation was determined by dual-luciferase reporter analysis and RNA immunoprecipitation. Results: Hypoxia resulted in proliferation inhibition, cycle arrest, apoptosis, inflammatory reaction, and oxidative stress in HRMECs. SAL attenuated hypoxia-induced HRMECs injury via increasing cell proliferation, and mitigating cycle arrest, apoptosis, inflammatory reaction, and oxidative stress. MiR-138 expression was enhanced by hypoxia, and decreased via SAL stimulation. MiR-138 upregulation reversed the influence of SAL on hypoxia-induced HRMECs injury. ROBO4 was targeted via miR-138. ROBO4 overexpression weakened the role of miR-138 in HRMECs injury. The PI3K/AKT/mTOR pathway was inactivated under hypoxic condition, and SAL increased the activation of PI3K/AKT/mTOR pathways by decreasing miR-138. Conclusions: SAL protected against hypoxia-induced HRMECs injury through regulating miR-138/ROBO4 axis, indicating the protective potential of SAL in retinopathies.