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1.
Vestn Oftalmol ; 137(5): 57-67, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34726859

RESUMO

Purpose - to investigate functional and morphological effects of peptide bioregulator (Retinalamin) in modeling of photochemical damage to rabbit retina. MATERIAL AND METHODS: The study was conducted on 36 rabbits (72 eyes) randomized into 4 equal groups: two experimental groups received parabulbar injections of Retinalamin («Geropharm¼, Russia) in each eye in dosages of 0.25 mg/kg in a course of 10 days starting from day 1 and day 10 of the experiment, respectively, and two control groups that received injections of normal solution with the same regimen. To simulate photochemical damage to the retina, exposure to light with a wavelength of 405 nm, a power density of 5 mW/cm2 and daily exposure time of 4 h was performed for 20 days. Multifocal and flicker 30 Hz electroretinogram (mfERG and fERG) were recorded, and histological studies of retina samples with quantitative assessment of retinal cells apoptosis by the TUNEL method were conducted before, as well as 10, 20 and 30 days after the start of light exposure. RESULTS: Ophthalmoscopic signs of light-induced retinal degeneration were revealed 6-10 days after start of exposure in all groups. When registering mfERG and fERG in all groups, there was a significant decrease in the amplitude of N1 and P1 peaks, retinal density of the bioelectric response of the P1 component, as well as the amplitude of fERG on days 10 and 20 after the beginning of light exposure (p<0.001 in comparison with the background values), and a slight increase in the indicators on day 30. Histological examination revealed a significant decrease in the number of cells in the outer nuclear layer and an increase in the proportion of apoptotic cells in the outer and inner nuclear layers on days 10 and 20 of the experiment, with a decrease on day 30 (after cessation of light exposure). Comparison of the groups receiving Retinalamin injections from days 1 or 10 of light exposure between themselves and the control groups revealed no significant differences in any of the studied parameters (p>0.05). CONCLUSION: No significant functional and morphological evidence of neuroprotective effects of Retinalamin were found in the model of photochemical damage to rabbit retinas.


Assuntos
Eletrorretinografia , Retina , Animais , Modelos Teóricos , Peptídeos , Coelhos
2.
Vestn Oftalmol ; 137(5): 114-121, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34726865

RESUMO

Unilateral pigmentary retinopathy (PR) is a rare, atypical form of hereditary retinal pathology. Different types of secondary retinopathy associated with various non-hereditary diseases, trauma or intoxication can imitate unilateral PR. Therefore, it is important to determine the cause of visual disorders and differentiate between unilateral and asymmetric PR. The article presents an example of using modern structural and functional diagnostic methods that helped diagnose the asymmetric form of the disease in a patient with suspected unilateral PR.


Assuntos
Eletrorretinografia , Retinite Pigmentosa , Humanos , Retina/diagnóstico por imagem , Retinite Pigmentosa/complicações , Retinite Pigmentosa/diagnóstico , Tomografia de Coerência Óptica , Acuidade Visual
3.
Invest Ophthalmol Vis Sci ; 62(14): 8, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34757417

RESUMO

Purpose: Current melphalan-based regimens for intravitreal chemotherapy for retinoblastoma vitreous seeds are effective but toxic to the retina. Thus, alternative agents are needed. Based on the known biology of histone deacetylases (HDACs) in the retinoblastoma pathway, we systematically studied whether the HDAC inhibitor belinostat is a viable, molecularly targeted alternative agent for intravitreal delivery that might provide comparable efficacy, without toxicity. Methods: In vivo pharmacokinetic experiments in rabbits and in vitro cytotoxicity experiments were performed to determine the 90% inhibitory concentration (IC90). Functional toxicity by electroretinography and structural toxicity by optical coherence tomography (OCT), OCT angiography, and histopathology were evaluated in rabbits following three injections of belinostat 350 µg (2× IC90) or 700 µg (4× IC90), compared with melphalan 12.5 µg (rabbit equivalent of the human dose). The relative efficacy of intravitreal belinostat versus melphalan to treat WERI-Rb1 human cell xenografts in rabbit eyes was directly quantified. RNA sequencing was used to assess belinostat-induced changes in RB cell gene expression. Results: The maximum nontoxic dose of belinostat was 350 µg, which caused no reductions in electroretinography parameters, retinal microvascular loss on OCT angiography, or retinal degeneration. Melphalan caused severe retinal structural and functional toxicity. Belinostat 350 µg (equivalent to 700 µg in the larger human eye) was equally effective at eradicating vitreous seeds in the rabbit xenograft model compared with melphalan (95.5% reduction for belinostat, P < 0.001; 89.4% reduction for melphalan, P < 0.001; belinostat vs. melphalan, P = 0.10). Even 700 µg belinostat (equivalent to 1400 µg in humans) caused only minimal toxicity. Widespread changes in gene expression resulted. Conclusions: Molecularly targeted inhibition of HDACs with intravitreal belinostat was equally effective as standard-of-care melphalan but without retinal toxicity. Belinostat may therefore be an attractive agent to pursue clinically for intravitreal treatment of retinoblastoma.


Assuntos
Modelos Animais de Doenças , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Inoculação de Neoplasia , Retina/efeitos dos fármacos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Sulfonamidas/uso terapêutico , Animais , Anexina A5 , Antineoplásicos Alquilantes/uso terapêutico , Eletrorretinografia , Angiofluoresceinografia , Inibidores de Histona Desacetilases/farmacocinética , Inibidores de Histona Desacetilases/toxicidade , Ácidos Hidroxâmicos/farmacocinética , Ácidos Hidroxâmicos/toxicidade , Injeções Intravítreas , Dose Máxima Tolerável , Melfalan/uso terapêutico , Coelhos , Retina/fisiologia , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/fisiopatologia , Retinoblastoma/diagnóstico , Retinoblastoma/fisiopatologia , Estudos Retrospectivos , Sulfonamidas/farmacocinética , Sulfonamidas/toxicidade , Tomografia de Coerência Óptica , Corpo Vítreo/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Transl Vis Sci Technol ; 10(12): 3, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605876

RESUMO

Purpose: The purpose of this study was to present normative data of optical coherence tomography (OCT), electrophysiological, and ocular biometry parameters and their correlation in minipigs. Methods: Eighty-eight eyes of 44 minipigs underwent full-field electroretinogram (ERG) recording and ocular biometry. However, 10 eyes of 6 minipigs were excluded because of poor OCT image quality. The thickness of the retinal sublayers was measured on a vertical line at 5 locations with a 1 mm interval from the disc margin to the dorsal periphery and at 10 locations on the visual streak. Visual evoked potentials (VEPs) were measured in 15 eyes of 8 minipigs. Results: All minipigs were female with a mean age and axial length of 13.83 ± 10.56 months and 20.33 ± 0.88 mm, respectively. The implicit time of the a-wave and b-wave in scotopic 3.0 ERGs was longer than that in photopic 3.0 ERG. The implicit time of the n2-wave and p2-wave in VEP was 25.67 ± 7.41 ms and 52.96 ± 10.38 ms, respectively. The total retinal layer (TRL) and nerve fiber layer (NFL) became thinner near the periphery. The inner retinal sublayers near the visual streak were thicker than those at other locations. Central TRL and NFL thickness on visual streak was 223.06 ± 23.19 µm and 74.03 ± 13.93 µm, respectively. The temporal TRL and NFL on the visual streak were thicker than those on the nasal side. Conclusions: The normative electrophysiological and OCT parameters used in our study can be used as reference data in further pig studies. Translational Relevance: This study presents normative data of minipigs, which are adequate animal models for preclinical studies.


Assuntos
Eletrorretinografia , Potenciais Evocados Visuais , Animais , Feminino , Humanos , Fibras Nervosas , Retina/diagnóstico por imagem , Suínos , Porco Miniatura
5.
J Neurodev Disord ; 13(1): 45, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625026

RESUMO

BACKGROUND: Disturbances in sensory function are an important clinical feature of neurodevelopmental disorders such as fragile X syndrome (FXS). Evidence also directly connects sensory abnormalities with the clinical expression of behavioral impairments in individuals with FXS; thus, positioning sensory function as a potential clinical target for the development of new therapeutics. Using electroretinography (ERG) and contrast sensitivity (CS), we previously reported the presence of sensory deficits in the visual system of the Fmr1-/y genetic mouse model of FXS. The goals of the current study were two-folds: (1) to assess the feasibility of measuring ERG and CS as a biomarker of sensory deficits in individuals with FXS, and (2) to investigate whether the deficits revealed by ERG and CS in Fmr1-/y mice translate to humans with FXS. METHODS: Both ERG and CS were measured in a cohort of male individuals with FXS (n = 20, 18-45 years) and age-matched healthy controls (n = 20, 18-45 years). Under light-adapted conditions, and using both single flash and flicker (repeated train of flashes) stimulation protocols, retinal function was recorded from individual subjects using a portable, handheld, full-field flash ERG device (RETeval®, LKC Technologies Inc., Gaithersburg, MD, USA). CS was assessed in each subject using the LEA SYMBOLS® low-contrast test (Good-Lite, Elgin, IL, USA). RESULTS: Data recording was successfully completed for ERG and assessment of CS in most individuals from both cohorts demonstrating the feasibility of these methods for use in the FXS population. Similar to previously reported findings from the Fmr1-/y genetic mouse model, individuals with FXS were found to exhibit reduced b-wave and flicker amplitude in ERG and an impaired ability to discriminate contrasts compared to healthy controls. CONCLUSIONS: This study demonstrates the feasibility of using ERG and CS for assessing visual deficits in FXS and establishes the translational validity of the Fmr1-/y mice phenotype to individuals with FXS. By including electrophysiological and functional readouts, the results of this study suggest the utility of both ERG and CS (ERG-CS) as complementary translational biomarkers for characterizing sensory abnormalities found in FXS, with potential applications to the clinical development of novel therapeutics that target sensory function abnormalities to treat core symptomatology in FXS. TRIAL REGISTRATION: ID-RCB number 2019-A01015-52 registered on the 17 May 2019.


Assuntos
Síndrome do Cromossomo X Frágil , Animais , Biomarcadores , Sensibilidades de Contraste , Eletrorretinografia , Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/genética , Masculino , Camundongos
6.
Invest Ophthalmol Vis Sci ; 62(13): 25, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34705026

RESUMO

Purpose: To provide a comprehensive analysis of light- and dark-adapted luminance thresholds and their associations with retinal structure in X-linked retinoschisis (XLRS). Methods: Nine subjects with XLRS and 10 visually-normal individuals participated. Threshold was measured at 15 locations along the horizontal meridian of the visual field at several adaptation levels (5 × 10-5 to 50 cd/m2) after dark-adaptation. The relationship between threshold and adaptation level across the field was described using a standard "threshold-versus-illuminance" model. Optical coherence tomography images were obtained and segmented to quantify outer nuclear layer (ONL+) and outer segment (OS+) thickness. A linear structure-function model was used to describe the relationship between threshold and the product of ONL+ and OS+ thickness. Results: For peripheral field measurements, thresholds were generally normal for most subjects with XLRS. All subjects had perifoveal and parafoveal threshold elevations under dark-adapted and high illuminance conditions, with thresholds at moderate illuminances being closer to normal. For foveal measurements, seven of nine subjects with XLRS had normal dark-adapted thresholds, and all had abnormally elevated high illuminance thresholds. Threshold-versus-illuminance curves in the fovea, parafovea, and perifovea were abnormally steep for subjects with XLRS, appearing similar to the normal peripheral field shape. Under both dark- and light-adapted conditions, threshold was predicted by ONL+ × OS+ thickness at nearly all field locations. Conclusions: Threshold elevation in XLRS is complex, depending on both the adaptation level and the visual field location. The pattern of threshold-versus-illuminance suggests that macular function in XLRS is similar to the periphery of controls.


Assuntos
Adaptação à Escuridão/fisiologia , Fóvea Central/diagnóstico por imagem , Retinosquise/fisiopatologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Campos Visuais/fisiologia , Adolescente , Adulto , Eletrorretinografia , Feminino , Fóvea Central/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Adulto Jovem
7.
Invest Ophthalmol Vis Sci ; 62(13): 8, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34643661

RESUMO

Purpose: Cell-based therapy development for geographic atrophy (GA) in age-related macular degeneration (AMD) is hampered by the paucity of models of localized photoreceptor and retinal pigment epithelium (RPE) degeneration. We aimed to characterize the structural and functional deficits in a laser-induced nonhuman primate model, including an analysis of the choroid. Methods: Macular laser photocoagulation was applied in four macaques. Fundus photography, optical coherence tomography (OCT), dye angiography, and OCT-angiography were conducted over 4.5 months, with histological correlation. Longitudinal changes in spatially resolved macular dysfunction were measured using multifocal electroretinography (MFERG). Results: Lesion features, depending on laser settings, included photoreceptor layer degeneration, inner retinal sparing, skip lesions, RPE elevation, and neovascularization. The intralesional choroid was degenerated. The normalized mean MFERG amplitude within lesions was consistently lower than control regions (0.94 ± 0.35 vs. 1.10 ± 0.27, P = 0.032 at month 1, 0.67 ± 0.22 vs. 0.83 ± 0.15, P = 0.0002 at month 2, and 0.97 ± 0.31 vs. 1.20 ± 0.21, P < 0.0001 at month 3.5). The intertest variation of mean MFERG amplitudes in rings 1 to 5 ranged from 13.0% to 26.0% in normal eyes. Conclusions: Laser application in this model caused localized outer retinal, RPE, and choriocapillaris loss. Localized dysfunction was apparent by MFERG in the first month after lesion induction. Correlative structure-function testing may be useful for research on the functional effects of stem cell-based therapy for GA. MFERG amplitude data should be interpreted in the context of relatively high intertest variability of the rings that correspond to the central macula. Sustained choroidal insufficiency may limit long-term subretinal graft viability in this model.


Assuntos
Eletrorretinografia/métodos , Angiofluoresceinografia/métodos , Atrofia Geográfica/patologia , Segmento Externo das Células Fotorreceptoras da Retina/patologia , Tomografia de Coerência Óptica/métodos , Animais , Modelos Animais de Doenças , Fundo de Olho , Atrofia Geográfica/fisiopatologia , Macaca fascicularis , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/fisiopatologia , Acuidade Visual
8.
Invest Ophthalmol Vis Sci ; 62(13): 9, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34643665

RESUMO

Purpose: To evaluate differences by sex in the neuroretina of rats with chronic glaucoma over 24 weeks of follow-up, and to assess by sex the influence on neurodegeneration of different methods of inducing ocular hypertension. Methods: Forty-six Long-Evans rats-18 males and 28 females-with induced chronic glaucoma were analyzed. Glaucoma was achieved via 2 models: repeatedly sclerosing the episcleral veins (9 male/14 female) or by injecting poly(lactic-co-glycolic acid) microspheres measuring 20 to 10 µm (Ms20/10) into the anterior chamber (9 male/14 female). The IOP was measured weekly by tonometer; neuroretinal function was recorded by dark/light-adapted electroretinography at baseline and weeks 12 and 24; and structure was analyzed by optical coherence tomography using the retina posterior pole, retinal nerve fiber layer and ganglion cell layer protocols at baseline and weeks 8, 12, 18, and 24. Results: Males showed statistically significant (P < 0.05) higher IOP in both chronic glaucoma models, and greater differences were found in the episcleral model at earlier stages. Males with episclerally induced glaucoma showed a statistically higher increase in retinal thickness in optical coherence tomography recordings than females and also when comparing Ms20/10 at 12 weeks. Males showed a higher percentage of retinal nerve fiber layer thickness loss in both models. Ganglion cell layer thickness loss was only detected in the Ms20/10 model. Males exhibited worse dark/light-adapted functionality in chronic glaucoma models, which worsened in the episcleral sclerosis model at 12 weeks, than females. Conclusions: Female rats with chronic glaucoma experienced lower IOP and structural loss and better neuroretinal functionality than males. Sex and the ocular hypertension-inducing method influenced neuroretinal degeneration.


Assuntos
Glaucoma/complicações , Degeneração Retiniana/etiologia , Células Ganglionares da Retina/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Eletrorretinografia , Feminino , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Masculino , Fibras Nervosas/patologia , Ratos , Ratos Long-Evans , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/fisiopatologia , Fatores de Tempo , Tomografia de Coerência Óptica/métodos
9.
Indian J Ophthalmol ; 69(11): 3235-3240, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34708779

RESUMO

Purpose: To examine (i) the retinal structure and function using optical coherence tomography angiography (OCTA) and multifocal electroretinography (mfERG), respectively, in eyes with and without nonproliferative diabetic retinopathy (NPDR), (ii) and their interrelationship between retinal structure (OCTA) and function (mfERG) in the two groups independently. Methods: This was a prospective observational study. One hundred twenty-one eligible participants with type 2 diabetes with No DR (n = 89), or with mild or moderate NPDR (n = 32) underwent ophthalmic examination, ultrawide field-view fundus photography, OCTA, and mfERG. Group differences were assessed using a Mann-Whitney U test. Correlations were assessed using Spearman's rho. Results: There were no significant differences in OCTA measures between the two groups. The mfERG P1 implicit times (rings 1-6) were significantly delayed and P1 response densities in rings 5 and 6 were significantly lower in participants with NPDR compared to those with No DR. In those with No DR, P1 implicit times in almost all rings were delayed in relation to lower vessel density and perfusion (maximum variance noted was 13%). In individuals with NPDR, the P1 response density in rings 2 and 3 showed a positive nonsignificant correlation with macular perfusion. Conclusion: In those with diabetes with No DR, retinal neuronal function is influenced by lower macular vessel density and perfusion. The retinal neuronal function is abnormal in individuals with NPDR compared to those with No DR and is not correlated with OCT angiometric measures, suggesting the likelihood of a different retinal structural correlate.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Retinopatia Diabética/diagnóstico , Eletrorretinografia , Angiofluoresceinografia , Humanos , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica
10.
Indian J Ophthalmol ; 69(11): 3241-3248, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34708780

RESUMO

Purpose: To evaluate the change in broadband (W/W), red on blue (R/B), and blue on yellow (B/Y) photopic negative response (PhNR) in patients with diabetes mellitus with no diabetic retinopathy (no DR) and different stages of DR and compare it with age-matched controls. This study was performed to provide a single PhNR protocol that can be used for early diagnosis of DR. Methods: It was a cross-sectional case-control study done in a hospital setup. Patients with diabetes with no DR and different stages of DR with no other associated ocular pathologies were included. Age-matched controls with no retinal pathologies were also included for comparison. All subjects underwent detailed ophthalmic examination and W/W, R/B, and B/Y electroretinography. Fifty control eyes and 52 treatment naïve eyes of 52 patients with diabetes [no DR = 11, mild nonproliferative diabetic retinopathy (NPDR) =11, moderate NPDR = 10, severe NPDR = 9, and proliferative DR = 11] were included in the study. Results: On comparing the ERG responses in patients with diabetes and age-matched controls, a significant reduction (P < 0.05) was noted in the amplitudes of a-wave (39.78 ± 11.34 µV vs. 67.28 ± 12.88 µV), b-wave (116.25 ± 45.25 vs. 134.39 ± 28.78 µV), W/W PhNR (33.86 ± 17.33 vs. 67.18 ± 15.99 µV), R/B PhNR (28.77 ± 15.85 vs. 53.48 ± 14.15 µV), and B/Y PhNR (55.04 ± 32.63 vs. 104.79 ± 24.37 µV). Post hoc analysis revealed that all the eyes in the diabetic group, including those with no DR, had a significantly reduced PhNR amplitude (P < 0.05) when compared with controls. PhNR was found to reduce in amplitude with increasing severity of DR (P < 0.05), with more significance in B/Y. Receiver operating characteristic showed highest area under the curve in B/Y PhNR (94%, P < 0.001), with maximum sensitivity and specificity of 88% and 87%, respectively. Conclusion: Changes in the amplitude and implicit time of ERG can reflect the severity of DR. PhNR amplitudes, especially B/Y PhNR, appear to be significantly reduced even in eyes with no DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Estudos de Casos e Controles , Estudos Transversais , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Eletrorretinografia , Humanos , Células Ganglionares da Retina
12.
Medicina (Kaunas) ; 57(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34577815

RESUMO

We report a unique case of coexisting pigmentary retinopathy and ocular toxoplasmosis in a young male patient. A 23-year-old man presented with sudden visual deterioration in the left eye (LE). The fundus findings revealed bone spicule-shaped pigment deposits, a slightly pale optic disc, arteriole constriction, cystoid macular edema with an epiretinal membrane, and two small inflammatory chorioretinal scars in the right eye, with a concentric narrowing of the visual field and a nonrecordable multifocal electroretinogram (ERG). An active inflammatory lesion at the border of a pre-existing chorioretinal scar in the macula was found in the LE, with a central scotoma in the visual field. Moreover, the patient tested positive for anti-Toxoplasma gondii immunoglobulin G antibodies and showed positive results in polymerase chain reaction testing of aqueous humor. Fluorescein angiography revealed hyperfluorescence in the early phase with fluorescein leakage. A multifocal ERG of the LE showed selective loss of responses from the central 10 degrees. Genetic testing revealed heterozygosity in the RP1 and CELSR1 genes. Our case illustrates challenges in the diagnosis of unilateral pigmentary retinopathy. Based on the typical toxoplasmic lesions in the LE and two scars likely caused by inflammation, our patient was diagnosed with pigmentary retinopathy probably related to toxoplasmosis. Genetic consultation did not confirm the diagnosis of retinitis pigmentosa, but more advanced tests might be needed to definitively exclude it.


Assuntos
Retinite Pigmentosa , Toxoplasmose Ocular , Adulto , Eletrorretinografia , Humanos , Masculino , Retina , Retinite Pigmentosa/diagnóstico , Retinite Pigmentosa/genética , Toxoplasmose Ocular/complicações , Toxoplasmose Ocular/diagnóstico , Campos Visuais , Adulto Jovem
13.
J Affect Disord ; 295: 453-462, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34507226

RESUMO

BACKGROUND: Developing easy-to-access biomarkers is crucial in Major Depressive Disorder. The retina has already been suggested as relevant. However, there is a need for a global and local assessment of whole retinal function using a reproducible, standardized protocol allowing for comparison across studies. Our aim is to assess whole retinal function in patients with actual unipolar Major Depressive Episode (MDE) using pattern, flash and multifocal electroretinogram (ERG) according to the International Society for Clinical Electrophysiology of Vision standardized protocols. METHODS: We assessed retinal function in 14 males and females with MDE, diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders, and in age- and sex-matched healthy controls. RESULTS: Comparing the patients with the controls, we observed the following using multifocal ERG: a significant increase in N1 peak time in ring 3 and a decrease in P1 amplitude in ring 2; using pattern ERG: a significant increase in P50 peak time; using flash ERG: a decrease in a- and b-wave peak time and an increase in the b-wave amplitude in dark-adapted 3.0, a decrease in a- and b-wave peak time and an increase in both wave amplitudes in light-adapted 3.0, and a decrease in the b-wave peak time in light-adapted flicker. LIMITATIONS: Sample size. Contribution of pharmacological treatments to the outcomes cannot be formally excluded. CONCLUSIONS: Patients with MDE exhibit delayed signaling in the central retina and hyperreactivity to light in the periphery. Central retinal function may be a marker of psychomotor retardation and cognitive impairment in MDE.


Assuntos
Transtorno Depressivo Maior , Eletrorretinografia , Feminino , Humanos , Masculino , Estimulação Luminosa , Retina
14.
Sensors (Basel) ; 21(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34577270

RESUMO

Analysis of biomedical signals is a very challenging task involving implementation of various advanced signal processing methods. This area is rapidly developing. This paper is a Part III paper, where the most popular and efficient digital signal processing methods are presented. This paper covers the following bioelectrical signals and their processing methods: electromyography (EMG), electroneurography (ENG), electrogastrography (EGG), electrooculography (EOG), electroretinography (ERG), and electrohysterography (EHG).


Assuntos
Eletrorretinografia , Processamento de Sinais Assistido por Computador , Eletromiografia , Eletroculografia
15.
Invest Ophthalmol Vis Sci ; 62(12): 14, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34529004

RESUMO

Purpose: Argonaute proteins are key players in small RNA-guided gene silencing processes. Ago2 is the member of the Argonaute subfamily with slicer endonuclease activity and is critical for microRNA homeostasis and indispensable for biological development. However, the impact of Ago2 dysregulation in the retina remains to be fully explored. In this study, we studied the role of Ago2 in mouse retina. Methods: We explored the function of Ago2 in the mouse retina through an adeno-associated virus-mediated Ago2 disruption mouse model. An ERG was carried out to determine the retinal function. Spectral domain optical coherence tomography, fundus photographs, and immunostaining were performed to investigate the retinal structure. A quantitative RT-PCR assay was used to determine the expression of noncoding RNAs. Results: Both silencing and overexpression of Ago2 in mouse retina resulted in significant retinal morphological alterations and severe impairment of retinal function, mainly with a thinned outer nuclear layer, shortened inner segment/outer segment, and diminished ERG responses. Furthermore, Ago2 disruption resulted in alterations of noncoding RNAs in retina. Conclusions: Our finding demonstrated that Ago2 interruption led to severe retinal degeneration, suggested that Ago2 homeostasis contributed to retinal structural and functional maintenance.


Assuntos
Proteínas Argonauta/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Degeneração Retiniana/genética , Animais , Proteínas Argonauta/biossíntese , Modelos Animais de Doenças , Eletrorretinografia , Camundongos Endogâmicos C57BL , Retina , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/metabolismo , Tomografia de Coerência Óptica/métodos
16.
Elife ; 102021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550876

RESUMO

Eukaryotes generally display a circadian rhythm as an adaption to the reoccurring day/night cycle. This is particularly true for visual physiology that is directly affected by changing light conditions. Here we investigate the influence of the circadian rhythm on the expression and function of visual transduction cascade regulators in diurnal zebrafish and nocturnal mice. We focused on regulators of shut-off kinetics such as Recoverins, Arrestins, Opsin kinases, and Regulator of G-protein signaling that have direct effects on temporal vision. Transcript as well as protein levels of most analyzed genes show a robust circadian rhythm-dependent regulation, which correlates with changes in photoresponse kinetics. Electroretinography demonstrates that photoresponse recovery in zebrafish is delayed in the evening and accelerated in the morning. Functional rhythmicity persists in continuous darkness, and it is reversed by an inverted light cycle and disrupted by constant light. This is in line with our finding that orthologous gene transcripts from diurnal zebrafish and nocturnal mice are often expressed in an anti-phasic daily rhythm.


Assuntos
Ritmo Circadiano/efeitos da radiação , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Células Fotorreceptoras Retinianas Cones/efeitos da radiação , Animais , Arrestinas/genética , Arrestinas/metabolismo , Escuridão , Eletrorretinografia , Feminino , Receptor Quinase 1 Acoplada a Proteína G/genética , Receptor Quinase 1 Acoplada a Proteína G/metabolismo , Luz , Transdução de Sinal Luminoso , Masculino , Camundongos , Modelos Animais , Células Fotorreceptoras de Vertebrados/metabolismo , Proteínas RGS/genética , Proteínas RGS/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Visão Ocular/efeitos da radiação , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
17.
Invest Ophthalmol Vis Sci ; 62(12): 28, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34581725

RESUMO

Purpose: To investigate the relationship between retinal structure and macular function in eyes screened for hydroxychloroquine (HCQ) toxicity. Methods: Participants referred for hydroxychloroquine retinopathy screening with spectral domain optical coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) testing were included in the analysis. Amplitude and implicit time of mfERG N1 and P1 responses were included in the analysis. Ring ratios were computed for amplitude values as the ratio of rings 1-3:5 (R1-3:R5). A control group of healthy participants was included for comparison of SD-OCT metrics. Results: Sixty-three eyes screened for HCQ retinopathy and 30 control eyes were analyzed. The outer nuclear layer (ONL) was significantly thinner in HCQ patients in the foveal (P = 0.008), parafoveal (P < 0.0001), and perifoveal (P < 0.0001) regions. The HCQ cohort was further divided into two subgroups according to the presence of structural clinically detectable retinopathy (i.e., structural damage as detected by multimodal imaging). HCQ eyes without retinopathy had a thinner ONL thickness in the foveal (P = 0.032), parafoveal (P < 0.0001), and perifoveal (P < 0.0001) regions and a thinner inner nuclear layer (INL) in the parafoveal region (P = 0.045 versus controls). Structural changes in HCQ patients without retinopathy were significantly associated with macular function as R2:R5 ring ratio of mfERG P1 amplitude was associated with INL (P = 0.002) and ONL (P = 0.044) thicknesses, and R3:R5 ring ratio of P1 amplitude was associated with ONL thickness (P = 0.004). Conclusions: Our results suggest that structural alterations secondary to HCQ toxicity may occur in the absence of clinically detectable retinopathy, and this may reflect in an impaired macular function.


Assuntos
Antirreumáticos/toxicidade , Hidroxicloroquina/toxicidade , Retina/fisiopatologia , Doenças Retinianas/fisiopatologia , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Eletrorretinografia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Retina/efeitos dos fármacos , Doenças Retinianas/induzido quimicamente , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Campos Visuais/fisiologia
18.
Exp Eye Res ; 211: 108762, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34499916

RESUMO

Ceramides are bioactive compounds that play important roles in regulating cellular responses to extracellular stimuli and stress. Previous studies have shown that ceramides contribute to retinal degeneration associated with ischemic and ocular hypertensive stress. Acid sphingomyelinase (ASMase) is one of the major enzymes responsible for the stress-induced generation of ceramides. The goals of this study are to investigate the effects of ceramides on retinal ganglion cells (RGCs) and of ASMase inhibition in ocular hypertensive mice. Induced pluripotent stem cell (iPSC)-derived RGCs and primary cultures of human optic nerve head astrocytes were used to characterize the response to C2-ceramide. Microbead-induced ocular hypertension in the ASMase heterozygote mouse model was used to confirm the physiological relevance of in vitro studies. In mice, RGC function and morphology were assessed with pattern ERG (pERG) and immunofluorescence. The addition of C2-ceramide to iPSC-derived RGCs produced a significant concentration- and time-dependent reduction in cell numbers when compared to control cultures. While the addition of C2-ceramide to astrocytes did not affect viability, it resulted in a 2.6-fold increase in TNF-α secretion. The addition of TNF-α or conditioned media from C2-ceramide-treated astrocytes to RGC cultures significantly reduced cell numbers by 56.1 ± 8.4% and 24.7 ± 4.8%, respectively. This cytotoxic response to astrocyte-conditioned media was blocked by TNF-α antibody. In ASMase heterozygote mice, functional and morphological analyses of ocular hypertensive eyes reveal significantly less RGC degeneration when compared with hypertensive eyes from wild-type mice. These results provide evidence that ceramides can induce RGC cell death by acting directly, as well as indirectly via the secretion of TNF-α from optic nerve head astrocytes. In vivo studies in mice provide evidence that ceramides derived through the activity of ASMase contribute to ocular hypertensive injury. Together these results support the importance of ceramides in the pathogenesis of ocular hypertensive injury to the retina.


Assuntos
Ceramidas/toxicidade , Degeneração Retiniana/induzido quimicamente , Células Ganglionares da Retina/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Western Blotting , Contagem de Células , Morte Celular , Eletrorretinografia , Humanos , Células-Tronco Pluripotentes Induzidas , Pressão Intraocular , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hipertensão Ocular/metabolismo , Disco Óptico/citologia , Reação em Cadeia da Polimerase em Tempo Real , Degeneração Retiniana/metabolismo , Células Ganglionares da Retina/metabolismo , Esfingomielina Fosfodiesterase/metabolismo , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Cells ; 10(9)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34572141

RESUMO

Transcorneal electrical stimulation (TES) has emerged as a non-invasive neuromodulation approach that exerts neuroprotection via diverse mechanisms, including neurotrophic, neuroplastic, anti-inflammatory, anti-apoptotic, anti-glutamatergic, and vasodilation mechanisms. Although current studies of TES have mainly focused on its applications in ophthalmology, several lines of evidence point towards its putative use in treating depression. Apart from stimulating visual-related structures and promoting visual restoration, TES has also been shown to activate brain regions that are involved in mood alterations and can induce antidepressant-like behaviour in animals. The beneficial effects of TES in depression were further supported by its shared mechanisms with FDA-approved antidepressant treatments, including its neuroprotective properties against apoptosis and inflammation, and its ability to enhance the neurotrophic expression. This article critically reviews the current findings on the neuroprotective effects of TES and provides evidence to support our hypothesis that TES possesses antidepressant effects.


Assuntos
Córnea/fisiologia , Depressão/terapia , Terapia por Estimulação Elétrica/métodos , Animais , Córnea/metabolismo , Transtorno Depressivo/terapia , Eletrorretinografia/métodos , Humanos , Fármacos Neuroprotetores/metabolismo , Retina/metabolismo , Retina/fisiologia
20.
Photobiomodul Photomed Laser Surg ; 39(9): 581-586, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34546108

RESUMO

Objective: To evaluate the short-term result of retinal functional behavior in patients with dry age-related macular degeneration (AMD) corrected by photobiomodulation (PBM) with 670 nm light-emitting diode (LED) light. Materials and methods: Ten patients with dry AMD underwent a treatment consisting of nine PBM sessions with LED light of 670 nm with two cycles of 50 mW/cm2, producing 4 J/cm2 per dose in 88 sec. The studied eye was compared with the baseline (before therapy), and after nine PBM sessions, the following aspects were evaluated: best-corrected visual acuity (VA), retinal sensitivity, and characteristics of the correction area by the fundus automated perimetry using the Compass system. A functional and structural assessment of the retina was also performed using the multifocal electroretinography (ERG), optical coherence tomography (OCT), fluorescence retinography (FR), and autofluorescence (AF). All examinations were performed 1, 4, and 16 weeks after the therapy. The Chi-square and Student's t-tests were used for comparisons. The analyses followed the 95% confidence level (p-value ≤0.05). Results: The BCVA significantly improved, from an average of 1.1 to 0.98 LogMAR (p = 0.01). The visual field examination, according to the parameters of mean deviation, standard deviation, and index of deviation of background perimeter, showed a significant improvement of -12.6% to -10.6%, 10.54% to 9.89%, and 56% to 60%, respectively (p = 0.02, 0.03, and 0.02, respectively). No participant had an adverse effect during the follow-up period; neither did any participant experience abnormalities in OCT, ERG, FR, and AF findings. Conclusions: In this short-term study, the PBM technique in patients with dry AMD showed the potential to improve VA and macular perimetry without causing significant adverse events. A larger number of patients and a longer follow-up will be necessary to further assess the success of this technique in these patients.


Assuntos
Degeneração Macular , Eletrorretinografia , Humanos , Degeneração Macular/radioterapia , Retina/diagnóstico por imagem , Acuidade Visual , Testes de Campo Visual
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