RESUMO

Basal electroretinogram (ERG) oscillations have shown predictive value for modifiable risk factors for type 2 diabetes. However, their origin remains unknown. Here, we seek to establish the pharmacological profile of the low delta-like (δ1) wave in the mouse because it shows light sensitivity in the form of a decreased peak frequency upon photopic exposure. Applying neuropharmacological drugs by intravitreal injection, we eliminated the δ1 wave using lidocaine or by blocking all chemical and electrical synapses. The δ1 wave was insensitive to the blockade of photoreceptor input, but was accelerated when all inhibitory or ionotropic inhibitory receptors in the retina were antagonized. The sole blockade of GABAA, GABAB, GABAC, and glycine receptors also accelerated the δ1 wave. In contrast, the gap junction blockade slowed the δ1 wave. Both GABAA receptors and gap junctions contribute to the light sensitivity of the δ1 wave. We further found that the day light-activated neuromodulators dopamine and nitric oxide donors mimicked the effect of photopic exposure on the δ1 wave. All drug effects were validated through light flash-evoked ERG responses. Our data indicate that the low δ-like intrinsic wave detected by the non-photic ERG arises from an inner retinal circuit regulated by inhibitory neurotransmission and nitric oxide/dopamine-sensitive gap junction-mediated communication.

Assuntos

Diabetes Mellitus Tipo 2 , Dopamina , Camundongos , Animais , Dopamina/farmacologia , Fotofobia , Estimulação Luminosa , Retina , Eletrorretinografia , Neurotransmissores/farmacologia , Receptores de GABA-A , Ácido gama-Aminobutírico/farmacologia

RESUMO

Introduction: Perinatal asphyxia (PA) represents a major problem in perinatology and may cause visual losses, including blindness. We, and others, have shown that hypothermia prevents retinal symptoms associated to PA. In the present work, we evaluate whether a hypothermia mimetic small molecule, zr17-2, has similar effects in the context of PA. Methods: Four experimental groups were studied in male rats: Naturally born rats as controls (CTL), naturally born rats injected s.c. with 50 µL of 330 nmols/L zr17-2 (ZR), animals that were exposed to PA for 20 min at 37°C (PA), and rats that were exposed to PA and injected with zr17-2 (PA-ZR). Forty-five days after treatment, animals were subjected to electroretinography. In addition, morphological techniques (TUNEL, H&E, multiple immunofluorescence) were applied to the retinas. Results: A reduction in the amplitude of the a- and b-wave and oscillatory potentials (OP) of the electroretinogram (ERG) was detected in PA animals. Treatment with zr17-2 resulted in a significant amelioration of these parameters (p < 0.01). In PA animals, a large number of apoptotic cells was found in the GCL. This number was significantly reduced by treatment with the small molecule (p < 0.0001). In a similar way, the thickness of the inner retina and the intensity of GFAP immunoreactivity (gliosis) increased in PA retinas (p < 0.0001). These parameters were corrected by the administration of zr17-2 (p < 0.0001). Furthermore, injection of the small molecule in the absence of PA did not modify the ERG nor the morphological parameters studied, suggesting a lack of toxicity. Discussion: In conclusion, our results indicate that a single s.c. injection of zr17-2 in asphyctic neonates may provide a novel and efficacious method to prevent the visual sequelae of PA.

RESUMO

PURPOSE: To present electroretinogram findings in extensive macular atrophy with pseudodrusen (EMAP) and describe associated systemic factors. DESIGN: Retrospective case series. METHODS: Data on medical history, visual symptoms, multimodal imaging findings, and visual field were collected from the medical records of patients with extensive macular atrophy with pseudodrusen who attended a visual electrophysiology laboratory. Electrophysiological tests, including full-field electroretinogram, multifocal electroretinogram and photopic negative response, were performed. RESULTS: Eighteen patients (10 [56%] females, age 49-66 years) were included. Of these, 17 (94%) had a history of rheumatic fever in childhood and/or adolescence, 7 (39%) had cardiovascular disease, 4 (22%) had autoimmune disease, and 10 (56%) had inflammatory conditions. The primary visual complaints were nyctalopia (95%), followed by visual field loss (67%) and dyschromatopsia (67%). The key retinal findings included retinal pigmented epithelium atrophy in the macular region and subretinal drusenoid deposits. Regarding electrophysiological results, 100% of patients had abnormalities on multifocal electroretinogram, 94% displayed alterations in photopic negative response, and 78% showed changes in the full-field electroretinogram. CONCLUSIONS: In this cohort, electrophysiologic evaluation demonstrated diffuse retinal dysfunction affecting all layers of the retina in patients with EMAP. The disease is associated with immune-mediated systemic conditions, chiefly rheumatic fever.

Assuntos

Degeneração Macular , Drusas Retinianas , Febre Reumática , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Estudos Retrospectivos , Drusas Retinianas/diagnóstico , Drusas Retinianas/complicações , Febre Reumática/complicações , Eletrorretinografia , Degeneração Macular/complicações , Degeneração Macular/diagnóstico , Atrofia/complicações , Tomografia de Coerência Óptica/métodos

RESUMO

Introduction: Diabetes mellitus describes a metabolic disorder of multiple etiologies, characterized by chronic hyperglycemia, which induces a series of molecular events capable of leading to microvascular damage, affecting the blood vessels of the retina, causing diabetic retinopathy. Studies indicate that oxidative stress plays a central role in complications involving diabetes. Açaí (Euterpe oleracea) has attracted much attention given its antioxidant capacity and potential associated health benefits in preventing oxidative stress, one of the causes of diabetic retinopathy. The objective of this work was to evaluate the possible protective effect of açaí (E. oleracea) on the retinal function of mice with induced diabetes, based on full field electroretinogram (ffERG). Methods: We opted for mouse models with induced diabetes by administration of a 2% alloxan aqueous solution and treatment with feed enriched with açaí pulp. The animals were divided into 4 groups: CTR (received commercial ration), DM (received commercial ration), DM + açaí (E. oleracea-enriched ration) and CTR + açaí (E. oleracea-enriched ration). The ffERG was recorded three times, 30, 45 and 60 days after diabetes induction, under scotopic and photopic conditions to access rod, mixed and cone responses, in addition to monitoring the weight and blood glucose of the animals during the study period. Statistical analysis was performed using the two-way ANOVA test with Tukey's post-test. Results: Our work obtained satisfactory results with the ffERG responses in diabetic animals treated with açaí, where it was observed that there was no significant decrease in the b wave ffERG amplitude of this group over time when compared to the results of the Diabetic group not treated with açaí, which showed a significant reduction of this ffERG component. Discussion: The results of the present study show, for the first time, that treatment with an açaí-enriched diet is effective against the decrease in the amplitude of visual electrophysiological responses in animals with induced diabetes, which opens a new horizon for the prevention of retinal damage in diabetic individuals from treatment with açaí base. However, it is worth mentioning that our findings consist of a preliminary study and further researches and clinical trials are needed to examine açaí potential as an alternative therapy for diabetic retinopathy.

RESUMO

Introducción: La retinopatía asociada a melanoma (RAM) es un desafío para el equipo tratante de pacientes oncológicos debido a la inespecificidad del cuadro clínico y a la dificultad de realizar exámenes que ofrezcan un diagnóstico. Métodos: Paciente 55 años, sexo femenino con diagnóstico de melanoma, consulta por escotoma central asociado a síntomas visuales positivos. Resultados: Examen oftalmológico dentro de rangos normales. Electrorretinograma (ERG) estándar muestra respuesta máxima electronegativa en ambos ojos, sugerente de RAM. Discusión: El reconocimiento temprano de RAM mediante ERG tiene importancia diagnóstica, permitiendo iniciar tratamiento temprano y reducir el riesgo irreversible de daño a la retina.

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Introduction: Melanoma-associated retinopathy (MAR) is a challenge for the oncology team due to the non-specific clinical presentation and the associated difficulty of performing indicative tests for diagnosis. Methods: A 55-year-old female patient initially diagnosed with melanoma consults due to vision with central scotoma associated with positive visual symptoms. Results: Ophthalmological examination within normal ranges. Standard electroretinogram (ERG) shows the maximum electronegative response in both eyes, suggesting MAR. Discussion: The early recognition of MAR by ERG has diagnostic importance because it would allow a possible early treatment and could reduce the risk of irreversible retina damage.

RESUMO

PURPOSE: To describe a case of retinitis pigmentosa and nanophthalmos in a patient with attenuated Hunter's syndrome. METHODS: Fundus photography, total field electroretinogram, ultrasound, computerized visual field examination, biochemical examination and genetic testing were obtained. RESULTS: The fundus exam showed diffuse arteriolar attenuation, optic disc with regular contours, and pigment agglomerates like "bone spicules" in the middle periphery. Ultrasound examination revealed scleral thickening and short axial diameter in both eyes. The total field electroretinogram exam showed a subnormal result with greater impairment of the scotopic phase of the exam. Computerized visual field examination demonstrated a diffuse reduction in retinal sensitivity in the periphery. Biochemical examination showed increased urine glycosaminoglycan excretion and iduronate-2-sulphatase activity (IDS) deficiency in leukocytes, confirming the type II mucopolysaccharidosis. Molecular analysis revealed a novel missense mutation (p.A77D) in the IDS gene. CONCLUSION: The case report is about a patient presented an attenuated form of the syndrome, with no cognitive impairment. Ophthalmologic follow-up is still an important part of multidisciplinary treatment for Hunter's syndrome.

Assuntos

Microftalmia , Mucopolissacaridose II , Retinose Pigmentar , Humanos , Mucopolissacaridose II/complicações , Mucopolissacaridose II/diagnóstico , Mucopolissacaridose II/terapia , Microftalmia/complicações , Microftalmia/diagnóstico , Microftalmia/genética , Eletrorretinografia , Retinose Pigmentar/complicações , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genética , Mutação de Sentido Incorreto

RESUMO

Introduction: Ocular and periocular traumatisms may result in loss of vision. Our previous work showed that therapeutic hypothermia prevents retinal damage caused by traumatic neuropathy. We also generated and characterized small molecules that elicit the beneficial effects of hypothermia at normal body temperature. Here we investigate whether one of these mimetic molecules, zr17-2, is able to preserve the function of eyes exposed to trauma. Methods: Intraorbital optic nerve crush (IONC) or sham manipulation was applied to Sprague-Dawley rats. One hour after surgery, 5.0 µl of 330 nmol/L zr17-2 or PBS, as vehicle, were injected in the vitreum of treated animals. Electroretinograms were performed 21 days after surgery and a- and b-wave amplitude, as well as oscillatory potentials (OP), were calculated. Some animals were sacrificed 6 days after surgery for TUNEL analysis. All animal experiments were approved by the local ethics board. Results: Our previous studies showed that zr17-2 does not cross the blood-ocular barrier, thus preventing systemic treatment. Here we show that intravitreal injection of zr17-2 results in a very significant prevention of retinal damage, providing preclinical support for its pharmacological use in ocular conditions. As previously reported, IONC resulted in a drastic reduction in the amplitude of the b-wave (p < 0.0001) and OPs (p < 0.05), a large decrease in the number of RGCs (p < 0.0001), and a large increase in the number of apoptotic cells in the GCL and the INL (p < 0.0001). Interestingly, injection of zr17-2 largely prevented all these parameters, in a very similar pattern to that elicited by therapeutic hypothermia. The small molecule was also able to reduce oxidative stress-induced retinal cell death in vitro. Discussion: In summary, we have shown that intravitreal injection of the hypothermia mimetic, zr17-2, significantly reduces the morphological and electrophysiological consequences of ocular traumatism and may represent a new treatment option for this cause of visual loss.

RESUMO

PURPOSE: To investigate ocular safety of intravitreal metoprolol in eyes with central serous chorioretinopathy. METHODS: Five eyes of five patients diagnosed with chronic central serous chorioretinopathy (cCSC) previously treated unsuccessfully with oral spironolactone, micropulse laser and intravitreal anti-vascular endothelial growth factor agents were enrolled and received off-label intravitreal metoprolol (50 µg/0.05 ml). Baseline and follow-up examinations included measurement of best-corrected visual acuity (BCVA), intraocular pressure, anterior chamber cellular/flare scores, vitritis classification, fluorescein and indocyanine green angiography, spectral domain optical coherence tomography and electroretinography (ERG), recorded by means of DTL electrodes and following the standard suggested by the International Society for Clinical Electrophysiology of Vision (ISCEV). The total follow-up period was 4 weeks. RESULTS: There were no significant differences between baseline and follow-up ERG parameters: scotopic or photopic, a- and b-wave amplitude and implicit time, nor oscillatory potentials amplitude, or whatsoever. No intraocular inflammation sign was observed. In addition, BCVA showed small improvement in 4 or kept baseline values in 1 patient. The subretinal and/or intraretinal fluid volume reduced in all patients at 1 month after treatment. CONCLUSION: Patients with refractory cCSC treated with intravitreal 50 µg/0.05 ml metoprolol showed no signs of acute ocular toxicity, along with intraretinal fluid reduction and slight BCVA improvement 1 month after injection. This data suggest that intravitreal metoprolol may be a safe alternative for cCSC.

Assuntos

Coriorretinopatia Serosa Central , Humanos , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/tratamento farmacológico , Metoprolol/uso terapêutico , Angiofluoresceinografia , Acuidade Visual , Eletrorretinografia , Tomografia de Coerência Óptica , Resultado do Tratamento , Injeções Intravítreas , Estudos Retrospectivos

RESUMO

PURPOSE: To report retinal function findings on the choroidal nevus. METHODS: Prospective descriptive case series of 7 patients (n = 7 eyes) presenting a melanocytic choroidal lesion consistent with choroidal nevus and no other ocular disease. Baseline evaluation included measurement of best-corrected visual acuity (BCVA), color and near-infrared fundus pictures, and spectral-domain OCT (Heidelberg Engineering). Retinal function was tested with microperimetry (MAIA; CenterVUE, Padova) using a standard grid (µP1) and a linear grid (µP2) that distribute test points on retinal areas that overlaid the choroidal lesion as well as lesion-free areas equidistantly to the fovea in 3 parallel lines. mfERG was performed following the International Society for Clinical Electrophysiology of Vision (ISCEV) recommendation using a 61-hexyagon protocol. RESULTS: BCVA was 20/25 (0.1 logMAR) or better in all 7 eyes. Microperimetry showed central stable fixation on all eyes, with mean ± SE sensitivity threshold significantly decreased on retinal areas overlaying the lesions (µP1): 21.8 ± 0.6 dB versus 25.2 ± 0.9 dB on nonaffected retinal areas (p < 0.001). Sensitivity was also decreased on µP2: 23.7 ± 0.2 dB for areas overlying the nevi and 25.7 ± 0.3 dB for the nonaffected retina (p < 0.001). mfERG responses showed no focal amplitude or implicit-time changes on the retina in the topographical region corresponding to the nevus for all patients. CONCLUSION: Our results indicate that choroidal nevi may cause significant retinal sensitivity impairment, as shown by microperimetry, but preserved mfERG response indicates that the retinal function may be only partially impaired.

RESUMO

Perinatal asphyxia (PA) can cause retinopathy and different degrees of visual loss, including total blindness. In a rat model of PA, we have previously shown a protective effect of hypothermia on the retina when applied simultaneously with the hypoxic insult. In the present work, we evaluated the possible protective effect of hypothermia on the retina of PA rats when applied immediately after delivery. Four experimental groups were studied: Rats born naturally as controls (CTL), animals that were exposed to PA for 20 min at 37°C (PA), animals exposed to PA for 20 min at 15°C (HYP), and animals that were exposed to PA for 20 min at 37°C and, immediately after birth, kept for 15 min at 8°C (HYP-PA). To evaluate the integrity of the visual pathway, animals were subjected to electroretinography at 45 days of age. Molecular (real time PCR) and histological (immunohistochemistry, immunofluorescence, TUNEL assay) techniques were applied to the eyes of all experimental groups collected at 6, 12, 24, and 48 h, and 6 days after birth. PA resulted in a significant reduction in the amplitude of the a- and b-wave and oscillatory potentials (OP) of the electroretinogram. All animals treated with hypothermia had a significant correction of the a-wave and OP, but the b-wave was fully corrected in the HYP group but only partially in the HYP-PA group. The number of TUNEL-positive cells increased sharply in the ganglion cell layer of the PA animals and this increase was significantly prevented by both hypothermia treatments. Expression of the cold-shock proteins, cold-inducible RNA binding protein (CIRP) and RNA binding motif protein 3 (RBM3), was undetectable in retinas of the CTL and PA groups, but they were highly expressed in ganglion neurons and cells of the inner nuclear layer of the HYP and HYP-PA groups. In conclusion, our results suggest that a post-partum hypothermic shock could represent a useful and affordable method to prevent asphyxia-related vision disabling sequelae.

RESUMO

BACKGROUND: Choroidal hemangioma is a visual threatening condition for which treatments is neither uniform nor widely available. New management options are necessary. The purpose of this study is to assess the safety and early outcome of intravitreal metoprolol tartrate in five patients with CCH. METHODS: Five eyes of five patients diagnosed with subfoveal or peripapillary CCH and unsuccessfully treated with intravitreal anti-VEGF agents were enrolled and received off-label intravitreal injections of metoprolol (50µg/0.05 ml). Baseline and follow-up evaluations included best-corrected visual acuity, intraocular pressure measurement, assessment of anterior chamber cellular score/flare and vitritis, retinography, fundus autofluorescence, and ERG. Patients were followed for a period of 30 days. Statistical analysis involved comparison of pre- and post-treatment findings using a paired t-test. RESULTS: There was no significant difference in all ERG parameters regarding a- and b-wave amplitude and implicit time, and oscillatory potentials' maximal amplitude. There were no significant changes in visual acuity. None of the patients developed clinical signs of intraocular inflammation. The subretinal and/or intraretinal fluid improved in 3 out of 5 patients 4 weeks after the metoprolol injection. CONCLUSIONS: Patients with CCH treated with a single injection of 50µg/0.05ml intravitreal metoprolol injections showed no signs of acute ocular toxicity. This pilot study did not assess long-term retinal toxicity, different concentrations, drug resistance, and complications from repeated-intravitreal injections.

Assuntos

Neoplasias da Coroide , Neovascularização de Coroide , Hemangioma , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/tratamento farmacológico , Neovascularização de Coroide/tratamento farmacológico , Angiofluoresceinografia , Seguimentos , Humanos , Injeções Intravítreas , Metoprolol/uso terapêutico , Projetos Piloto , Tomografia de Coerência Óptica

RESUMO

The mdx52 mouse model of Duchenne muscular dystrophy (DMD) is lacking exon 52 of the DMD gene that is located in a hotspot mutation region causing cognitive deficits and retinal anomalies in DMD patients. This deletion leads to the loss of the dystrophin proteins, Dp427, Dp260 and Dp140, while Dp71 is preserved. The flash electroretinogram (ERG) in mdx52 mice was previously characterized by delayed dark-adapted b-waves. A detailed description of functional ERG changes and visual performances in mdx52 mice is, however, lacking. Here an extensive full-field ERG repertoire was applied in mdx52 mice and WT littermates to analyze retinal physiology in scotopic, mesopic and photopic conditions in response to flash, sawtooth and/or sinusoidal stimuli. Behavioral contrast sensitivity was assessed using quantitative optomotor response (OMR) to sinusoidally modulated luminance gratings at 100% or 50% contrast. The mdx52 mice exhibited reduced amplitudes and delayed implicit times in dark-adapted ERG flash responses, particularly in their b-wave and oscillatory potentials, and diminished amplitudes of light-adapted flash ERGs. ERG responses to sawtooth stimuli were also diminished and delayed for both mesopic and photopic conditions in mdx52 mice and the first harmonic amplitudes to photopic sine-wave stimuli were smaller at all temporal frequencies. OMR indices were comparable between genotypes at 100% contrast but significantly reduced in mdx52 mice at 50% contrast. The complex ERG alterations and disturbed contrast vision in mdx52 mice include features observed in DMD patients and suggest altered photoreceptor-to-bipolar cell transmission possibly affecting contrast sensitivity. The mdx52 mouse is a relevant model to appraise the roles of retinal dystrophins and for preclinical studies related to DMD.

Assuntos

Distrofia Muscular de Duchenne/fisiopatologia , Percepção Visual/fisiologia , Animais , Eletrorretinografia , Camundongos , Camundongos Endogâmicos mdx , Transmissão Sináptica/fisiologia

RESUMO

PURPOSE: To report electroretinographic (ERG) findings in advanced glaucoma treated with a single intravitreal injection of bone marrow-derived mesenchymal stem cells (MSCs). METHODS: Intravitreal injection of autologous MSCs (1 × 106 cells) was performed in 2 eyes from 2 patients with open-angle glaucoma in advanced stage of optic neuropathy (ClinicalTrials.gov, NCT02330978, 01.05.2015): cup/disk ratio worse than 0.9, visual field mean deviation index lower than - 15 dB, visual acuity of light perception, but controlled intraocular pressure. ERG tests were recorded at baseline and week 1, 4 and 48 after injection, using DTL electrodes following the ISCEV standard: After dark adaptation, ERG was elicited using white flashes of 0.01 cd.s/m2 and 3.0 cd.s/m2, followed by 10-min light adaptation (30 cd/m2) and stimuli of 3.0 cd.s/m2 and 30 Hz flicker. RESULTS: Patients did not show improvement on visual acuity or visual field after treatment. At baseline, ERG responses showed typical findings for advanced glaucoma, with a- and b-wave amplitude and latency within normative range, but reduced photopic negative responses. No noteworthy changes were observed on ERG responses for both cases up to 1 week after treatment, but at day 15, one patient showed retinal detachment with proliferative vitreoretinopathy and was removed from the trial. The other patient kept ERG responses stable throughout study period. CONCLUSION: Although no ERG response changes were observed after MSCs injection in one case, the complication observed on the second one, along with the lack of visual function improvement, warrants further studies involving modified MSCs to treat ocular disorders, including glaucoma. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02330978- missed in pdf.

Assuntos

Glaucoma de Ângulo Aberto , Glaucoma , Células-Tronco Mesenquimais , Medula Óssea , Eletrorretinografia , Humanos , Injeções Intravítreas

RESUMO

PURPOSE: To determine normative values, intra- and inter-session variability for a range of parameters derived from the photopic negative response (PhNR) using a handheld mini-Ganzfeld stimulator in healthy normal adults. METHODS: Light-adapted flash full-field electroretinograms (ERGs) were recorded from healthy individuals with no visual complaints, visual acuity equal to or better than 0.0 logMAR (20/20 Snellen), and negative family history for visual diseases. ERGs were recorded from both eyes using a DTL® type fiber electrode after dilation of the pupils with instillation of 1 drop of tropicamide eye drops (1%). The full-field PhNR stimulus conditions were produced by a LED-based ColorBurst™ (Diagnosys LLC, Lowell, MA, USA) handheld stimulator. Red flashes of 1, 5 and 7 cd.s/m2 on a blue background of 10 cd/m2 were presented. A-wave, b-wave and PhNR amplitude (determined by both baseline to trough-BT and peak to trough-PT) and peak times were analyzed. Normal limits were determined as 5% percentile for amplitudes and 95% percentile for latencies. Intra- and inter-session variability were assessed with Wilcoxon signed-rank test, intraclass correlation coefficient (ICC) and the coefficient of variability (COV). RESULTS: Normative limits for PhNR amplitude (µV) using 1, 5 and 7 cd.s./m2 stimuli were, respectively: 20.81; 18.06 and 19.60 for BT and 69.11; 77.98; 76.51 for PT. Peak times (ms) normative limits for 1, 5 and 7 cd.s/m2 intensities were, respectively, 65.98; 78.20 and 77.96. Overall, intra-session variability assessed by coefficients of variation ranged from 1.35 to 10.28%. Inter-session variability disclosed significant intraclass correlation values for all PhNR parameters only for 1 cd.s/m2 stimuli. CONCLUSIONS: The normative values provided by this study are clinically helpful in the diagnosis of inner retinal disorders, especially those affecting retinal ganglion cells such as glaucoma and other optic neuropathies. Further studies, including a larger sample with variable age range would extend the validity of the current results.

Assuntos

Visão de Cores/fisiologia , Eletrorretinografia/métodos , Retina/fisiologia , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Microeletrodos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estimulação Luminosa , Valores de Referência , Células Ganglionares da Retina/fisiologia , Adulto Jovem

RESUMO

Purpose: Disturbances that affect the inside of the eyeball tend to be highly harmful since they compromise the homeostasis of this organ. Alongside this, the eyeball has several anatomical barriers that prevent the entry of substances. This way, diseases that affect the retina are among those that present greater difficulty in the treatment. In many cases, abnormal proliferation of blood vessels (neovascularization) occurs from the lower layers of the retina. This process damages its structure physiologically and anatomically, causing the rapid and irreversible loss of visual capacity. This work aims to develop nanosuspensions of quantum dots (QDs) conjugated to bevacizumab. Methods: Two types of QDs were produced by aqueous route, stabilized with chitosan conjugated to bevacizumab. The antiangiogenic activity was evaluated in the chorioallantoic membrane model, in which results indicated discrete activity at the doses tested. Samples were assessed for their biosafety in animals, after intravitreal administration, by means of electroretinography (ERG), intraocular pressure (IOP) measurement, histological, morphometric, and immunohistochemical evaluation. Results: No significant alterations were detected in ERG that suggests damage to retinal function by the samples. No significant changes in IOP were also detected. The histological sections did not show signs of acute inflammation, although there was evidence of late retinal damage. The immunohistochemical analysis did not detect any apoptotic bodies. Conclusion: Preliminary results suggest that QDs present potential applicability in ocular therapy, and it is necessary to better characterize their in vivo behavior and to optimize their dosage.

Assuntos

Inibidores da Angiogênese/farmacologia , Bevacizumab/farmacologia , Pontos Quânticos/uso terapêutico , Retina/patologia , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Animais , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Membrana Corioalantoide/efeitos dos fármacos , Contenção de Riscos Biológicos/normas , Eletrorretinografia/métodos , Imuno-Histoquímica/métodos , Pressão Intraocular/efeitos dos fármacos , Injeções Intravítreas , Masculino , Modelos Animais , Nanopartículas/química , Nanopartículas/uso terapêutico , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/tratamento farmacológico , Pontos Quânticos/administração & dosagem , Pontos Quânticos/química , Ratos , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/metabolismo , Suspensões/administração & dosagem , Suspensões/química , Suspensões/farmacocinética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/farmacologia , Fator A de Crescimento do Endotélio Vascular/imunologia

RESUMO

Resumo Apresentamos um caso de distrofia macular oculta bilateral, em paciente de 70 anos com queixa de baixa acuidade visual progressiva, sem achados fundoscópicos ou angiográficos justificáveis. Foram realizados exames de imagem do sistema nervoso central que afastaram lesões expansivas e testes eletrofisiológicos que sugeriram diagnóstico.

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Abstract We report a case of bilateral occult macular dystrophy in a 70-year-old woman with progressive low visual acuity, without justifiable fundoscopic or angiographic findings. Imaging tests were done to excluding expansive lesions and electrophysiological tests that suggested the diagnosis.

Assuntos

Humanos , Feminino , Idoso , Angiofluoresceinografia/métodos , Acuidade Visual , Tomografia de Coerência Óptica/métodos , Eletrofisiologia/métodos , Eletrorretinografia/métodos , Degeneração Macular/diagnóstico , Diagnóstico Diferencial

RESUMO

Spiders are a large group of arthropods and nearly omnipresent in warm and temperate climates. They rely on tactile and visual information to hunt and breed, but compared with their mechanical senses, little is known about their visual systems. In this study, we analyzed the visual spectral sensitivity of the Chilean recluse spider Loxosceles laeta, a synanthropic species posing a significant threat to humans, using electroretinogram recordings of its three eye types and open field tests with localized chromatic illumination for behavioral analysis. The electroretinogram displayed two sensitivity peaks in the ultraviolet and green ranges, and no differences were observed between the three eye types and between male and female specimens. Selective chromatic adaptation reduced overall light sensitivity, but did not support the expression of more than one type of rhodopsin in photoreceptors. The open field tests revealed a preference for corners over side areas, and an increased exploration of open field areas illuminated by shorter wavelength (violet to green) light compared with non-illuminated areas, while no behavioral responses to red and near-infrared light were observed. These data suggest that L. laeta has monochromatic vision without spectral specializations in its three secondary eye pairs.

Assuntos

Percepção de Cores , Aranhas/fisiologia , Animais , Feminino , Masculino

RESUMO

Purpose: To evaluate the intermediate and outer retina of patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) using OCT and multifocal electroretinography (mf-ERG). Methods: Patients with MS (n = 30), NMOSD (n = 30), and healthy controls (n = 29) underwent visual field (VF), OCT, and mf-ERG testing. The eyes were distributed into 5 groups: MS with or without history of ON (MS+ON, MS-ON), NMOSD with or without ON (NMOSD+ON, NMOSD-ON), and controls. The thickness of the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer was measured. mf-ERG P1 and N1 responses were registered and grouped in 3 sets of rings. The groups were compared using GEE models, and effect size (ES) calculated. Results: Compared to controls, GCL and IPL thickness was significantly smaller in MS+ON (both p < 0.01), MS-ON (p < 0.01 and p = 0.015, respectively), NMOSD+ON (both p < 0.01) and NMOSD-ON (p = 0.03 and p = 0.018, respectively). ES was >0.80. mRNFL was smaller in three of the above groups (p < 0.01, p < 0.001, and p = 0.028; ES > 0.80) but not in MS-ON eyes (p = 0.18). No significant difference was observed for the remaining layers. Compared to controls, P1 and N1 peak times were shorter in MS (p-values in the range 0.049-0.002, ES < 0.50; and 0.049-0.010; ES < 0.50, respectively) but not in NMOSD. These abnormalities were strongly correlated with intermediate and outer retinal layer thickness. Conclusions: mf-ERG data suggest outer retinal abnormalities in MS, but not in NMOSD. Our results may help understand how the two conditions differ regarding retinal damage.

RESUMO

PURPOSE: To prospectively evaluate the dynamic changes of the full-field electroretinogram (ff-ERG) and its association with inflammatory signs in patients with Vogt-Koyanagi-Harada disease (VKHD) followed up after acute onset. METHODS: Twelve acute VKHD patients, who were followed up for at least 24 months, were enrolled at a tertiary center from June 2011 to January 2017. Treatment consisted of intravenous methylprednisolone followed by 1 mg/kg/day of oral prednisone with a slow tapering associated with late non-steroidal immunosuppressive therapy in previously defined cases. Inflammation was systematically evaluated with clinical and posterior segment imaging (PSI) exams (fluorescein angiography, FA, indocyanine green angiography, ICGA, enhanced depth imaging optical coherence tomography, EDI-OCT). A ff-ERG was performed upon enrollment as well as at predefined intervals. Scotopic ff-ERG parameters changes between the 12th and 24th months defined the ERG-stable or ERG-worsening groups. "Flare" was defined as an appearance or worsening of inflammatory signs (after the initial 6 months following disease onset) under the predefined treatment protocol. RESULTS: ff-ERG parameters initially improved in all eyes; in the evaluation between the 12th and 24th months, ff-ERG results were stable in 17 eyes (71 %) and worsened in 7 eyes (29 %). Subnormal ff-ERG results were observed in 15 eyes (62 %) at the 24th month. On the other hand, the flare was observed in 8 eyes (33 %) as cells in the anterior chamber and in 24 eyes (100 %) as any PSI inflammatory sign. The ERG-worsening group presented thicker subfoveal choroid at the first month (p = 0.001) and fluctuations in choroidal thickness more often during follow-up when compared to the ERG-stable group (p = 0.02). CONCLUSIONS: Scotopic ff-ERG parameters worsened between the 12th and 24th months in a quarter of the patients. Subclinical inflammation detected as an increase in CT seems to be related to worsening in visual function measured with ffERG.

Assuntos

Eletrorretinografia/métodos , Retina/fisiopatologia , Síndrome Uveomeningoencefálica/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Corioide/patologia , Progressão da Doença , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Retina/diagnóstico por imagem , Fatores de Tempo , Tomografia de Coerência Óptica/métodos , Síndrome Uveomeningoencefálica/fisiopatologia , Adulto Jovem

RESUMO

Light pollution by artificial light, might accelerate retinal diseases and circadian asynchrony. The excess of light exposure is a growing problem in societies, so studies on the consequences of long-term exposure to low levels of light are needed to determine the effects on vision. The possibility to understand the molecular mechanisms of light damage will contribute to the knowledge about visual disorders related to defects in the phototransduction. Several animal models have been used to study retinal degeneration (RD) by light; however, some important aspects remain to be established. Previously, we demonstrated that cool white treatment of 200 lux light-emitting diode (LED) induces retinal transformation with rods and cones cell death and significant changes in opsin expression in the inner nuclear layer (INL) and ganglion cell layer (GCL). Therefore, to further develop describing the molecular pathways of RD, we have examined here the oxidative stress and the fatty acid composition in rat retinas maintained at constant light. We demonstrated the existence of oxidative reactions after 5 days in outer nuclear layer (ONL), corresponding to classical photoreceptors; catalase (CAT) enzyme activity did not show significant differences in all times studied and the fatty acid study showed that docosahexaenoic acid decreased after 4 days. Remarkably, the docosahexaenoic acid diminution showed a correlation with the rise in stearic acid indicating a possible association between them. We assumed that the reduction in docosahexaenoic acid may be affected by the oxidative stress in photoreceptors outer segment which in turn affects the stearic acid composition with consequences in the membrane properties. All these miss-regulation affects the photoreceptor survival through unknown mechanisms involved. We consider that oxidative stress might be one of the pathways implicated in RD promoted by light.