RESUMEN
BACKGROUND: Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H2) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H2 provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H2 on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice. METHODS: In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2-/-) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H2) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H2 under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining. RESULTS: Our results indicate that 3-4% H2 does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H2 prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H2 inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H2 plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H2 promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression. CONCLUSIONS: Collectively, our results indicate that H2 could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways.
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Modelos Animales de Enfermedad , Hidrógeno , Neuroglía , Oxígeno , Neovascularización Retiniana , Retinopatía de la Prematuridad , Animales , Hidrógeno/farmacología , Neovascularización Retiniana/tratamiento farmacológico , Neuroglía/efectos de los fármacos , Ratones , Retinopatía de la Prematuridad/tratamiento farmacológico , Ratones Endogámicos C57BL , Retina/efectos de los fármacos , Animales Recién Nacidos , Regeneración/efectos de los fármacos , Inmunohistoquímica , Vasos Retinianos/efectos de los fármacosRESUMEN
The hormone prolactin (PRL) is emerging as an important regulator of ocular blood vessels. PRL is pro-angiogenic and acquires anti-angiogenic properties after undergoing proteolytic cleavage to the PRL fragment, vasoinhibin. The vascularisation of the rodent retina develops after birth when it rapidly expands until completion at the end of the first postnatal week. Exposure of newborn mice to high oxygen levels lowers the rate of blood vessel growth. In the present study, we investigated whether PRL treatment modifies the vascularisation of the retina in newborn mice exposed to high oxygen or to normoxia and whether the retinal conversion of PRL to vasoinhibin may be altered in the neonate. Newborn mice and their nursing mothers were subjected to 75% oxygen or to normoxia from postnatal day (P) 6 to P8 (group 1) or from P2 to P5 (group 2). PRL (2 µg g-1 , i.p., twice a day) or vehicle was injected from P5 to P8 in group 1 and from P1 to P5 in group 2. PRL treatment reduced the retinal inhibition of blood vessel growth and the increase in vascular regression induced by hyperoxia as revealed by immunofluorescence staining of blood vessels and the expression of angiogenesis and apoptosis markers. The pro-angiogenic effect may involve a reduced conversion of PRL to vasoinhibin. Incubation of PRL with retinal extracts showed reduced activity of the PRL-cleaving protease, cathepsin D, in the neonate vs the adult retina that was further reduced under hyperoxia. PRL and the PRL receptor mRNA were expressed at higher levels in the retina at P8 than in the adult, whereas endogenous PRL was undetectable in the circulation at P8. We conclude that PRL has a pro-angiogenic effect in the neonate retina as a result of its reduced conversion to vasoinhibin and that PRL produced by the retina may help promote physiological vascularisation after birth.
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Hiperoxia , Neovascularización Fisiológica , Prolactina , Vasos Retinianos , Animales , Femenino , Masculino , Ratones , Embarazo , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Hiperoxia/patología , Neovascularización Fisiológica/efectos de los fármacos , Prolactina/sangre , Prolactina/metabolismo , Prolactina/farmacología , Receptores de Prolactina/efectos de los fármacos , Receptores de Prolactina/metabolismo , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/crecimiento & desarrollo , Retinopatía de la Prematuridad/patologíaRESUMEN
Retinal ischemia-reperfusion (rI/R) generates an oxidative condition causing the death of neuronal cells. Epigallocatechin 3-gallate (EGCG) has antioxidant and anti-inflammatory properties. Nonetheless, its correlation with the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) for the protection of the retina is unknown. We aimed to evaluate the neuroprotective efficacy of single-doses of EGCG in rI/R and its association with Nrf2/Ho-1 expression. In albino rabbits, rI/R was induced and single-doses of EGCG in saline (0-30 mg/kg) were intravenously administered to select an optimal EGCG concentration that protects from retina damage. To reach this goal, retinal structural changes, gliosis by glial fibrillary acidic protein (GFAP) immunostaining, and lipid peroxidation level by TBARS (thiobarbituric acid reactive substance) assay were determined. EGCG in a dose of 15 mg/kg (E15) presented the lowest levels of histological damage, gliosis, and oxidative stress in the studied groups. To determine the neuroprotective efficacy of E15 in a timeline (6, 24, and 48 h after rI/R), and its association with the Nrf2/HO-1 pathway, the following assays were done by immunofluorescence: apoptosis (TUNEL assay), necrosis (high-mobility group box-1; HMGB1), Nrf2, and HO-1. In addition, the Ho-1 mRNA (qPCR) and lipid peroxidation levels were evaluated. E15 showed a protective effect during the first 6 h, compared to 24 and 48 h after rI/R, as revealed by a decrease in the levels of all damage markers. Nuclear translocation Nrf2 and HO-1 staining were increased, including Ho-1 mRNA levels. In conclusion, a single dose of E15 decreases the death of neuronal cells induced by oxidative stress during the first 6 h after rI/R. This protective effect is associated with the nuclear translocation of Nrf2 and with an elevation of Ho-1 expression.
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Antioxidantes/uso terapéutico , Catequina/análogos & derivados , Fármacos Neuroprotectores/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Vasos Retinianos/efectos de los fármacos , Animales , Antioxidantes/farmacología , Apoptosis , Catequina/farmacología , Catequina/uso terapéutico , Hemo Oxigenasa (Desciclizante)/genética , Hemo Oxigenasa (Desciclizante)/metabolismo , Peroxidación de Lípido , Masculino , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Fármacos Neuroprotectores/farmacología , Conejos , Vasos Retinianos/metabolismo , Vasos Retinianos/patologíaRESUMEN
PURPOSE: To investigate retinal microvasculature changes in patients treated with anti-VEGF for macular edema secondary to branch retinal vein occlusion. METHODS: We examined 38 eyes of 19 patients for the study. We measured superficial and deep capillary plexus vessel densities (%), foveal avascular zone areas (mm2), and central macular thicknesses. RESULTS: Parafoveal superficial and deep capillary plexus values were significantly lower in eyes with branch retinal vein occlusion than in fellow eyes (p<0.001). We found a significant increase in parafoveal deep capillary plexus values after the anti-VEGF treatment (p=0.032). The mean foveal avascular zone was larger in eyes with branch retinal vein occlusion than in control eyes (p<0.001). The mean central macular thickness was significantly higher in eyes with branch retinal vein occlusion than in controls, and we observed a significant decrease in central macular thickness after anti-VEGF treatment (<0.001). In addition, the cystic structures in the deep capillary plexus regressed. CONCLUSION: Optical coherence tomography angiography enables qualitative and quantitative evaluations during follow-up of patients treated for branch retinal vein occlusion.
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Inhibidores de la Angiogénesis/uso terapéutico , Angiografía con Fluoresceína/métodos , Edema Macular/tratamiento farmacológico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Tomografía de Coherencia Óptica/métodos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Capilares/diagnóstico por imagen , Capilares/efectos de los fármacos , Capilares/patología , Femenino , Humanos , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/efectos de los fármacos , Mácula Lútea/patología , Edema Macular/diagnóstico por imagen , Edema Macular/etiología , Edema Macular/patología , Masculino , Persona de Mediana Edad , Valores de Referencia , Oclusión de la Vena Retiniana/complicaciones , Oclusión de la Vena Retiniana/diagnóstico por imagen , Oclusión de la Vena Retiniana/patología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/patología , Estudios Retrospectivos , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del Tratamiento , Agudeza VisualRESUMEN
PURPOSE: To investigated the effects of ginsenoside Rb1 on diabetic retinopathy in streptozotocin-induced diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of streptozotocin (80 mg/kg) in male Wistar rats. Ginsenoside Rb1 (20, 40 mg/kg) was injected (i.p.) once a day for 4 weeks. Then, using fundus photography, the diameter and vascular permeability of retinal vessels were investigated. Retinal histopathology was undertaken. Contents of malondialdehyde (MDA) and glutathione (GSH) in retinas were assayed. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione cysteine ligase catalytic subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM) were measured. RESULTS: Treatment with ginsenoside Rb1 attenuated the diabetes-induced increase in the diameter of retinal blood vessels. Ginsenoside Rb1 reduced extravasation of Evans Blue dye from retinal blood vessels. Ginsenoside Rb1 partially inhibited the increase in MDA content and decrease in GSH level in rat retinas. Nrf2 levels in the nuclei of retinal cells and expression of GCLC and GCLM were increased significantly in rats treated with ginsenoside Rb1. CONCLUSION: These findings suggest that ginsenoside Rb1 can attenuate diabetic retinopathy by regulating the antioxidative function in rat retinas.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Ginsenósidos/uso terapéutico , Animales , Masculino , Ratas , Ratas Wistar , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/patología , EstreptozocinaRESUMEN
Endothelial heterogeneity has important implications in health and disease. Molecular markers selectively expressed in the vasculature of different organs and tissues are currently being explored in targeted therapies with promising results in preclinical and clinical studies. Noteworthy is the role that combinatorial approaches such as phage display have had in identifying such markers by using phage as nanoparticles and surrogates for billions of different peptides, screening noninvasively the vascular lumen for binding sites. Here, we show that a new peptide motif that emerged from such combinatorial screening of the vasculature binds selectively to blood vessels in the brain in vivo but not to vessels in other organs. Peptides containing a conserved motif in which amino acids Phenylalanine-Arginine-Tryptophan (FRW) predominate could be visualized by transmission electron microscopy bound to the junctions between endothelial cells in all areas of the brain, including the optic nerve, but not in other barrier-containing tissues, such as intestines and testis. Remarkably, peptides containing the motif do not bind to vessels in the retina, implying an important molecular difference between these two vascular barriers. Furthermore, the peptide allows for in vivo imaging, demonstrating that new tools for studying and imaging the brain are likely to emerge from this motif.
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Secuencias de Aminoácidos , Encéfalo/metabolismo , Circulación Cerebrovascular/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Ligandos , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/metabolismo , Secuencia de Aminoácidos , Animales , Encéfalo/irrigación sanguínea , Técnicas de Visualización de Superficie Celular , Endotelio Vascular/ultraestructura , Femenino , Técnica del Anticuerpo Fluorescente , Ratones , Péptidos/química , Péptidos/metabolismo , Unión ProteicaRESUMEN
Abstract Purpose: To investigated the effects of ginsenoside Rb1 on diabetic retinopathy in streptozotocin-induced diabetic rats. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin (80 mg/kg) in male Wistar rats. Ginsenoside Rb1 (20, 40 mg/kg) was injected (i.p.) once a day for 4 weeks. Then, using fundus photography, the diameter and vascular permeability of retinal vessels were investigated. Retinal histopathology was undertaken. Contents of malondialdehyde (MDA) and glutathione (GSH) in retinas were assayed. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione cysteine ligase catalytic subunit (GCLC), and glutathione cysteine ligase modulatory subunit (GCLM) were measured. Results: Treatment with ginsenoside Rb1 attenuated the diabetes-induced increase in the diameter of retinal blood vessels. Ginsenoside Rb1 reduced extravasation of Evans Blue dye from retinal blood vessels. Ginsenoside Rb1 partially inhibited the increase in MDA content and decrease in GSH level in rat retinas. Nrf2 levels in the nuclei of retinal cells and expression of GCLC and GCLM were increased significantly in rats treated with ginsenoside Rb1. Conclusion: These findings suggest that ginsenoside Rb1 can attenuate diabetic retinopathy by regulating the antioxidative function in rat retinas.
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Animales , Masculino , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/patología , Ratas Wistar , Estreptozocina , Ginsenósidos/uso terapéuticoRESUMEN
Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat brain mitochondria (RBM). In SH-SY5Y cells, t-BOOH induced a significant reduction of cell viability as assessed by an MTT assay, and the reduction was effectively prevented by treatment with C-PC in the low micromolar concentration range. Transient ischemia in rat retinas was induced by increasing the intraocular pressure to 120mmHg for 45min, which was followed by 15min of reperfusion. This event resulted in a cell density reduction to lower than 50% in the inner nuclear layer (INL), which was significantly prevented by the intraocular pre-treatment with C-PC for 15min. In the RBM exposed to 3mM phosphate and/or 100µM Ca(2+), C-PC prevented in the low micromolar concentration range, the mitochondrial permeability transition as assessed by mitochondrial swelling, the membrane potential dissipation, the increase of reactive oxygen species levels and the release of the pro-apoptotic cytochrome c. In addition, C-PC displayed a strong inhibitory effect against an electrochemically-generated Fenton reaction. Therefore, C-PC is a potential neuroprotective agent against ischemic stroke, resulting in reduced neuronal oxidative injury and the protection of mitochondria from impairment.
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Fosfatos de Calcio/toxicidad , Isquemia/prevención & control , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ficocianina/farmacología , Vasos Retinianos/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Línea Celular Tumoral , Humanos , Isquemia/inducido químicamente , Isquemia/metabolismo , Masculino , Mitocondrias/metabolismo , Estrés Oxidativo/fisiología , Ficocianina/uso terapéutico , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Retina/efectos de los fármacos , Retina/metabolismo , Vasos Retinianos/metabolismo , terc-Butilhidroperóxido/toxicidadAsunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Enfermedades de la Retina/tratamiento farmacológico , Vasos Retinianos/efectos de los fármacos , Telangiectasia/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Femenino , Angiografía con Fluoresceína , Humanos , Inyecciones , Persona de Mediana Edad , Ranibizumab , Retina/patología , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/fisiopatología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/fisiopatología , Vasos Retinianos/patología , Telangiectasia/diagnóstico , Telangiectasia/fisiopatología , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Cuerpo VítreoRESUMEN
PURPOSE: To create a retinal neovascularization experimental model using intravitreal injection of microspheres loaded with latex-derived angiogenic fraction. METHODS: Thirty-two albino New Zealand rabbits, divided in 4 groups of 8 animals, were enrolled in this study. Rabbits in groups I, II, and III received one intravitreal injection of PLGA (L-lactide-co-glycolide) microspheres with 10, 30, and 50 microg of latex-derived angiogenic fraction into their right eyes, respectively, and group IV received 0.1 ml of microspheres without the angiogenic fraction. Weekly follow-up with ophthalmoscopy and fluorescein angiography was performed; the rabbits were sacrificed in the 4th week and their eyes processed for light microscopy. RESULTS: All eyes from group I demonstrated increased retinal vascular tortuosity, observed from 14 days after injection and maintained for 28 days, otherwise without new vessels detection. All group II eyes showed vascular changes similar to group I. Fifty percent of the eyes from group II rabbits developed retinal neovascularization 21 days after injection. All eyes from group III demonstrated significant vascular tortuosity and retinal new vessels 2 weeks after injection, progressing to fibrovascular proliferation and tractional retinal detachment. No vascular changes or retinal new vessels were observed in group IV eyes. Light microscopy confirmed the existence of new vessels previously seen on fluorescein angiography, in retinal sections adjacent to the optic disc, not observed in sections at the same area in the control group. CONCLUSION: Thirty- and 50-microg microspheres containing latex-derived angiogenic fraction injected into the vitreous cavity induced retinal neovascularization in rabbits.
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Inductores de la Angiogénesis/toxicidad , Modelos Animales de Enfermedad , Látex/toxicidad , Neovascularización Retiniana/inducido químicamente , Vasos Retinianos/efectos de los fármacos , Animales , Portadores de Fármacos , Femenino , Angiografía con Fluoresceína , Ácido Láctico , Microesferas , Oftalmoscopía , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Conejos , Neovascularización Retiniana/diagnóstico , Vasos Retinianos/patologíaRESUMEN
Propolis, a resinous substance collected by honeybees from various plant sources, has several pharmacological actions, such as anti-tumor and anti-inflammatory effects. The aim of this study was to evaluate the anti-angiogenic effects of a water extract of Brazilian green propolis (WEP) and its constituents, caffeoylquinic acid derivatives, against angiogenic processes in human umbilical vein endothelial cells (HUVECs) in vitro. We also examined the anti-angiogenic effects of WEP against retinal neovascularization in a murine oxygen-induced retinopathy model in vivo. WEP and its constituents significantly suppressed vascular endothelial growth factor (VEGF)-induced HUVEC proliferation, migration, and tube formation in vitro. WEP and its caffeoylquinic acid derivatives suppressed VEGF-stimulated phosphorylation of mitogen-activated protein kinase in HUVECs (versus VEGF alone). Moreover, WEP (300 mg/kg/day, subcutaneously for 5 days) significantly suppressed retinal neovascularization in the murine oxygen-induced retinopathy model. These data indicate that (i) WEP has angiostatic effects against angiogenic processes in vitro and in an in vivo model of murine oxygen-induced retinopathy and (ii) the inhibitory effects of WEP against in vitro angiogenesis are chiefly derived from its caffeoylquinic acid derivatives. Judging from these findings, WEP and its caffeoylquinic acid derivatives may represent candidates for preventive or therapeutic agents against diseases caused by angiogenesis.
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Inhibidores de la Angiogénesis/farmacología , Asteraceae , Própolis/química , Própolis/farmacología , Animales , Brasil , División Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Humanos , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Oxígeno , Fosforilación/efectos de los fármacos , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacología , Enfermedades de la Retina/etiología , Enfermedades de la Retina/fisiopatología , Vasos Retinianos/efectos de los fármacos , Venas Umbilicales/efectos de los fármacosRESUMEN
Diabetic retinopathy (DR) remains the major threat to sight in the working age population. Diabetic macular edema (DME) is a manifestation of DR that produces loss of central vision. Macular edema within 1 disk diameter of the fovea is present in 9% of the diabetic population. Proliferative diabetic retinopathy (PDR) is a major cause of visual loss in diabetic patients. In PDR, the growth of new vessels from the retina or optic nerve, is thought to occur as a result of vascular endothelial growth factor (VEGF) release into the vitreous cavity as a response to ischemia. Furthermore, VEGF increases vessel permeability leading to deposition of proteins in the interstitium that facilitate the process of angiogenesis and macular edema. This review demonstrates multiple benefits of intravitreal bevacizumab on DR including DME and PDR. The results indicate that intravitreal bevacizumab injections may have a beneficial effect on macular thickness and visual acuity (VA), independent of the type of macular edema that is present. Therefore, in the future this new treatment modality could replace or complement focal/grid laser photocoagulation in DME. In addition, in PDR, this new option could be an adjuvant agent to PRP so that more selective therapy may be applied.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Retinopatía Diabética/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Neovascularización Patológica/prevención & control , Cuerpo Vítreo/efectos de los fármacos , Anticuerpos Monoclonales Humanizados , Bevacizumab , Retinopatía Diabética/patología , Humanos , Edema Macular/patología , Nervio Óptico/efectos de los fármacos , Nervio Óptico/patología , Recurrencia , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/patología , Factor A de Crecimiento Endotelial Vascular/fisiología , Cuerpo Vítreo/irrigación sanguínea , Cuerpo Vítreo/fisiopatologíaRESUMEN
PURPOSE: To report the visual outcomes and ocular complications of intravitreal triamcinolone acetonide (IVTA) in the treatment of the nonproliferative stage of type II idiopathic parafoveal telangiectasia (IPT). METHODS: Retrospective, multicenter, uncontrolled interventional case series of 19 eyes of 14 consecutive patients with the nonproliferative stage of IPT that had undergone at least one intravitreal injection of 4 mg of triamcinolone acetonide. Demographic, medical, and ocular data were obtained through chart review. The main outcome measures included best-corrected visual acuity at several timepoints of follow up and ocular complications. RESULTS: At baseline the mean logMAR visual acuity was 0.83 +/- 0.41 (Snellen 20/135, range 0.3-2). After an average follow-up of 21.2 months (range 6-44 months), the mean logMAR visual acuity remained essentially unchanged from baseline. At 3 months, the logMAR visual acuity was 0.86 +/- 0.44 (Snellen 20/145, P = 0.8378), at 6 months 0.86 +/- 0.42 (Snellen 20/145, P = 0.8149), at 12 months 0.87 +/- 0.46 (Snellen 20/148, P > 0.9999), at 18 months 0.84 +/- 0.35 (Snellen 20/138, P = 0.8385), and at the last follow-up 0.82 +/- 0.44 (Snellen 20/132, P = 0.9301). Seven eyes were reinjected once. Ten of 19 eyes (53%) developed cataract (3 eyes underwent phacoemulsification and intraocular lens implantation) and 7 of 19 eyes (37%) had an elevated intraocular pressure, none of which required surgical treatment. CONCLUSION: IVTA does not seem to improve visual acuity in most eyes with the nonproliferative stage of IPT.
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Glucocorticoides/administración & dosificación , Enfermedades de la Retina/tratamiento farmacológico , Vasos Retinianos/efectos de los fármacos , Telangiectasia/tratamiento farmacológico , Triamcinolona Acetonida/administración & dosificación , Anciano , Femenino , Angiografía con Fluoresceína , Fóvea Central , Glucocorticoides/efectos adversos , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/diagnóstico , Vasos Retinianos/patología , Estudios Retrospectivos , Telangiectasia/diagnóstico , Resultado del Tratamiento , Triamcinolona Acetonida/efectos adversos , Agudeza Visual/efectos de los fármacos , Cuerpo VítreoRESUMEN
In the present study, the neuroprotective effect of blockers of voltage-dependent calcium channels (VDCC) and intracellular calcium stores on retinal ischemic damage induced by oxygen deprivation-low glucose insult (ODLG) was investigated. Retinal damage induced by ODLG was dependent on the calcium concentration in the perfusion medium. When incubated in medium containing 2.4 mM CaCl(2), cell death in ischemic retinal slices treated with blockers of VDCC, omega-conotoxin GVIA (1.0 microM), omega-conotoxin MVIIC (100 nM) and nifedipine (1.0 microM), was reduced to 62 +/- 2.3, 46 +/- 4.3 and 47 +/- 3.9%, respectively. In the presence of blockers of intracellular calcium stores, dantrolene (100 microM) and 2-APB (100 microM), the cell death was reduced to 46 +/- 3.2 and 55 +/- 2.9%, respectively. Tetrodotoxin (1.0 microM), reducing the extent of the membrane depolarization reduces the magnitude of calcium influx trough VDCC causing a reduction of the cell death to 55 +/- 4.3. Lactate dehydrogenase content of untreated ischemic retinal slices was reduced by 37% and treatment of ischemic slices with BAPTA-AM (100 microM) or 2-APB (100 microM) abolished the leakage of LDH. Dantrolene (100 microM) and nifedipine (1.0 microM) partially blocked the induced reduction on the LDH content of retinal ischemic slices. Histological analysis of retinal ischemic slices showed 40% reduction of ganglion cells that was prevented by BAPTA-AM or dantrolene. 2-APB partially blocked this reduction whilst nifedipine had no effect, p > 0.95. Conclusion Blockers of VDCC and intracellular calcium-sensitive receptors exert neuroprotective effect on retinal ischemia.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Calcio/metabolismo , Isquemia/prevención & control , Retina/efectos de los fármacos , Vasos Retinianos/efectos de los fármacos , Animales , Quelantes/farmacología , Glucosa/deficiencia , Técnicas In Vitro , Espacio Intracelular/metabolismo , Isquemia/metabolismo , Isquemia/patología , Microscopía Confocal , Oxígeno/fisiología , Ratas , Ratas Wistar , Retina/metabolismo , Retina/patologíaRESUMEN
BACKGROUND: Poland syndrome has been attributed to a process of vascular disruption, and exposure to misoprostol at 6-8 weeks of gestation has been shown to produce defects attributed to vascular disruption. Herein we report the first case of a patient with Poland syndrome associated with an aberrant subclavian artery and vascular abnormalities of the retina, whose mother used misoprostol during pregnancy. CASE: A White boy of 1 year and 7 months of age, whose mother used misoprostol during the second month of pregnancy, presented with bilateral epicanthal folds, aplasia of the sternocostal head of the pectoralis major muscle with a hypoplastic nipple on the right side, and asymmetry between the upper limbs. The results of an angiotomographic study showed the presence of an aberrant right subclavian artery. Ultrasonographic evaluation showed turbulence and a high peak in the diastolic velocity in both carotid arteries, suggesting stenosis. Ophthalmologic assessment disclosed an intense bilateral tortuosity of the retinal blood vessels, with arterialnarrowing and rarefaction of the retinal pigment epithelium. CONCLUSIONS: This case suggests that the mechanism of vascular disruption of misoprostol could be related to the aberrant subclavian artery and the observed Poland syndrome. His retinal findings are different from those in cases described thus far in the literature, and this pattern of anomaly has never been associated with a gestational exposure to misoprostol. The possibility of a relationship of the aberrant right subclavian artery and the pattern of blood flow verified in the carotid arteries with the eye fundus abnormalities could be causally related or simply coincidental.
Asunto(s)
Anomalías Inducidas por Medicamentos , Abortivos no Esteroideos/efectos adversos , Misoprostol/efectos adversos , Síndrome de Poland/inducido químicamente , Enfermedades de la Retina/inducido químicamente , Vasos Retinianos/efectos de los fármacos , Arteria Subclavia/anomalías , Femenino , Humanos , Lactante , Masculino , EmbarazoRESUMEN
Relato de caso de um paciente com telangiectasia justafoveal idiopática (TJI) tipo 1A, no olho direito, submetido a 4 mg de triancinolona intravítrea. O resultado foi avaliado por meio da acuidade visual e da tomografia de coerência óptica. A acuidade visual e a espessura retiniana macular medida na tomografia de coerência óptica, antes da injeção intravítrea de triancinolona, foram respectivamente de 20/100 e 569 æm e, após três semanas do tratamento foram de 20/60 e 371 æm e na sexta semana de 20/100 e 614 æm. A estabilização da parede vascular obtida com injeção intravítrea de triancinolona proporciona melhora transitória da visão e do edema macular em olhos com TJI-1A. Não foi demonstrada nenhuma ajuda permanente à fotocoagulação prévia.
Case report of one idiopathic juxtafoveal telangiectasis (IJT) 1A patient whose right eye was treated with a 4 mg intravitreal triamcinolone acetonide injection. The outcome was evaluated by visual acuity and optic coherence tomography. The visual acuity and the caliper retinal thickness before triamcinolone injection were respectively 20/100 and 569 æm, and 20/60 and 371 æm after three weeks and 20/100 and 614 æm after six week of follow-up. The stabilization of the vascular wall due to the intravitreal triamcinolone injection leads to a transitory improvement in vision and reduction in macular edema in the TJI 1A eyes. No permanent help by the photocoagulation could be shown.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Glucocorticoides/administración & dosificación , Enfermedades de la Retina/tratamiento farmacológico , Vasos Retinianos/efectos de los fármacos , Telangiectasia/terapia , Triamcinolona Acetonida/administración & dosificación , Inyecciones , Edema Macular/tratamiento farmacológico , Vasos Retinianos/patología , Factores de Tiempo , Agudeza Visual , Cuerpo Vítreo/efectos de los fármacosRESUMEN
PURPOSE: To characterize ocular manifestations of cat-scratch disease in HIV-positive patients. DESIGN: Retrospective case series study. METHODS: Records and photography of patients with the diagnosis of cat-scratch disease and HIV were reviewed. RESULTS: From 2001 and 2004 three patients with cat-scratch disease and HIV were identified. All patients presented with subretinal mass associated with an abnormal vascular network. Fluorescein angiography revealed this abnormal vascular network more clearly. All patients were treated with antibiotics alone with good response. CONCLUSIONS: Subretinal mass associated with abnormal vascular network is characteristic of cat-scratch disease in HIV-positive patients. Fluorescein angiography is important to characterize this vascular pattern, and patients may benefit from systemic treatment.
Asunto(s)
Enfermedad por Rasguño de Gato/diagnóstico , Infecciones Bacterianas del Ojo/diagnóstico , Seropositividad para VIH/diagnóstico , Enfermedades de la Retina/diagnóstico , Vasos Retinianos/patología , Adulto , Antibacterianos/uso terapéutico , Anticuerpos Antibacterianos/sangre , Bartonella henselae/inmunología , Enfermedad por Rasguño de Gato/tratamiento farmacológico , Enfermedad por Rasguño de Gato/microbiología , Ciprofloxacina/uso terapéutico , Doxiciclina/uso terapéutico , Quimioterapia Combinada , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Infecciones Bacterianas del Ojo/microbiología , Angiografía con Fluoresceína , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/microbiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/microbiología , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/microbiología , Estudios RetrospectivosRESUMEN
Case report of one idiopathic juxtafoveal telangiectasis (IJT) 1A patient whose right eye was treated with a 4 mg intravitreal triamcinolone acetonide injection. The outcome was evaluated by visual acuity and optic coherence tomography. The visual acuity and the caliper retinal thickness before triamcinolone injection were respectively 20/100 and 569 microm, and 20/60 and 371 microm after three weeks and 20/100 and 614 microm after six week of follow-up. The stabilization of the vascular wall due to the intravitreal triamcinolone injection leads to a transitory improvement in vision and reduction in macular edema in the TJI 1A eyes. No permanent help by the photocoagulation could be shown.
Asunto(s)
Glucocorticoides/administración & dosificación , Enfermedades de la Retina/tratamiento farmacológico , Vasos Retinianos/efectos de los fármacos , Telangiectasia/terapia , Triamcinolona Acetonida/administración & dosificación , Humanos , Inyecciones , Edema Macular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Vasos Retinianos/patología , Factores de Tiempo , Agudeza Visual , Cuerpo Vítreo/efectos de los fármacosRESUMEN
AIMS/HYPOTHESIS: Our aim was to compare the therapeutic effect of thalidomide and rosiglitazone on the prevention of diabetic retinopathy in streptozotocin-induced diabetic rats. METHODS: Male Holtzman rats of 6 to 8 weeks of age and weighing 170+/-30 g were randomly divided into four groups: control ( n=13), untreated diabetic ( n=17) and diabetic rats treated with thalidomide (200 mg kg(-1) day(-1)) ( n=8) or rosiglitazone (1 mg kg(-1) day(-1)) ( n=22) for 3 months. Diabetes was induced by streptozotocin with the rats having a body weight of 70 mg/kg. After treatment, vascular endothelial growth factor (VEGF) concentrations in ocular fluid were compared between the different groups, and retinal capillary basement membrane thickness was measured by electron microscopy. RESULTS: Higher VEGF concentrations in ocular fluid and thicker basement membranes were observed in untreated diabetic rats compared to the control rats. Similar VEGF concentrations and basement membrane thickness were observed for the thalidomide-treated group compared with the control group, whereas no difference in these parameters was observed between the rosiglitazone-treated rats and the control or untreated diabetic rats. CONCLUSIONS/INTERPRETATION: Our findings confirm the association between VEGF concentrations and diabetic retinopathy as suggested by other investigators. Thalidomide, but not rosiglitazone, was associated with the inhibition of basement membrane thickening and the blockade of the increase of VEGF in ocular fluid, thus representing a potential therapeutic drug for the prevention of diabetic retinopathy.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Humor Acuoso/metabolismo , Diabetes Mellitus Experimental/prevención & control , Diabetes Mellitus Experimental/fisiopatología , Retinopatía Diabética/prevención & control , Talidomida/uso terapéutico , Tiazolidinedionas/uso terapéutico , Animales , Capilares/efectos de los fármacos , Capilares/patología , Retinopatía Diabética/patología , Modelos Animales de Enfermedad , Hipoglucemiantes/uso terapéutico , Ratas , Ratas Sprague-Dawley , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/patología , Rosiglitazona , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
PURPOSE: To describe the clinical, angiographic and optical coherence tomography (OCT) findings of a patient with a large retinal capillary hemangioma who was treated by indocyanine green-mediated photothrombosis. Interventional case report. METHODS: An 18-year-old male patient was treated at a tertiary referral center with a novel laser-dye procedure that uses low-irradiance 810-nm laser and intravenous indocyanine green injection and was prospectively evaluated with fluorescein and indocyanine green angiography, as well as OCT. RESULTS: Vision improved from 20/125 to 20/32 + 1 at 1-year follow-up. Fundus photography showed marked reduction of a 3 disk diameters retinal capillary hemangioma. Both fluorescein and indocyanine green angiography demonstrated reduced tumor perfusion and narrowing of the lesion feeder and draining vessels as early as 5 days after indocyanine green-mediated photothrombosis; OCT showed immediate decrease in retinal elevation and complete resolution of subretinal fluid within 2 months of treatment. Minimal laser-induced effects were noted in the vicinity of the tumor. CONCLUSIONS: Photothrombosis using low-intensity, 810-nm light to direct laser energy continuously at the tumor after intravenous indocyanine green infusion was effective in restoring macular architecture and improving vision in a patient with a large peripheral retinal capillary hemangioma by means of substantial occlusion of the tumor vasculature and resolution of subretinal fluid.