RESUMO
We previously reported that 2-arachidonoylglycerol (2-AG) synthesis by diacylglycerol lipase (DAGL) and lysophosphatidate phosphohydrolase (LPAP) and hydrolysis by monoacylglycerol lipase (MAGL) in rod outer segments (ROS) from bovine retina were differently modified by light applied to the retina. Based on these findings, the aim of the present research was to evaluate whether 2-AG metabolism could be modulated by proteins involved in the visual process. To this end, ROS kept in darkness (DROS) or obtained in darkness and then subjected to light (BROS) were treated with GTPγS and GDPßS, or with low and moderate ionic strength buffers for detaching soluble and peripheral proteins, or soluble proteins, respectively. Only DAGL activity was stimulated by the application of light to the ROS. GTPγS-stimulated DAGL activity in DROS reached similar values to that observed in BROS. The studies using different ionic strength show that (1) the highest decrease in DROS DAGL activity was observed when both phosphodiesterase (PDE) and transducin α (Tα) are totally membrane-associated; (2) the decrease in BROS DAGL activity does not depend on PDE association to membrane, and that (3) MAGL activity decreases, both in DROS and BROS, when PDE is not associated to the membrane. Our results indicate that the bioavailability of 2-AG under light conditions is favored by G protein-stimulated increase in DAGL activity and hindered principally by Tα/PDE association with the ROS membrane, which decreases DAGL activity.
Assuntos
Ácidos Araquidônicos , Endocanabinoides , Glicerídeos , Segmento Externo da Célula Bastonete , Animais , Endocanabinoides/metabolismo , Ácidos Araquidônicos/metabolismo , Segmento Externo da Célula Bastonete/metabolismo , Bovinos , Glicerídeos/metabolismo , Transdução de Sinal Luminoso , Transducina/metabolismo , Luz , Lipase Lipoproteica/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Visão Ocular/fisiologia , Visão Ocular/efeitos dos fármacosRESUMO
Glaucoma is a blindness-causing disease that involves selective damage to retinal ganglion cells (RGCs) and their axons. A subset of RGCs expressing the photopigment melanopsin regulates non-image-forming visual system functions, such as pupillary light reflex and circadian rhythms. We analyzed the effect of melatonin on the non-image-forming visual system alterations induced by experimental glaucoma. For this purpose, male Wistar rats were weekly injected with vehicle or chondroitin sulfate into the eye anterior chamber. The non-image-forming visual system was analyzed in terms of (1) melanopsin-expressing RGC number, (2) anterograde transport from the retina to the olivary pretectal nucleus and the suprachiasmatic nuclei, (3) blue- and white light-induced pupillary light reflex, (4) light-induced c-Fos expression in the suprachiasmatic nuclei, (5) daily rhythm of locomotor activity, and (6) mitochondria in melanopsin-expressing RGC cells. Melatonin prevented the effect of experimental glaucoma on melanopsin-expressing RGC number, blue- and white light-induced pupil constriction, retina-olivary pretectal nucleus, and retina- suprachiasmatic nuclei communication, light-induced c-Fos expression in the suprachiasmatic nuclei, and alterations in the locomotor activity daily rhythm. In addition, melatonin prevented the effect of glaucoma on melanopsin-expressing RGC mitochondrial alterations. These results support that melatonin protected the non-image-forming visual system against glaucoma, probably through a mitochondrial protective mechanism.
Assuntos
Antioxidantes/administração & dosagem , Glaucoma/prevenção & controle , Melatonina/administração & dosagem , Células Ganglionares da Retina/efeitos dos fármacos , Visão Ocular/efeitos dos fármacos , Animais , Glaucoma/induzido quimicamente , Glaucoma/metabolismo , Luz/efeitos adversos , Masculino , Ratos , Ratos Wistar , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/metabolismo , Núcleo Supraquiasmático/efeitos dos fármacos , Núcleo Supraquiasmático/metabolismo , Visão Ocular/fisiologiaRESUMO
Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide. We conducted an observational study of 262 consecutive individuals (n = 344 eyes) with ocular toxoplasmosis who were followed over a 34-month period. Most subjects were T. gondii IgG + /IgM- (n = 242; 92.4%; 317 eyes), and 140 eyes (40.7%) had active lesions. For eyes in which retinal lesions were active at recruitment and best-corrected visual acuity (BCVA) could be measured (n = 133), 21.0% (n = 28) remained blind (BCVA below 20/400) after inflammation resolved. In these eyes, atypical ocular toxoplasmosis (OR 4.99; 95% CI 1.14-22.85; p = 0.0330), macular lesion (OR 9.95; 95% CI 2.45-47.15; p = 0.0019) and any complication (OR 10.26; 95% CI 3.82-30.67; p < 0.0001) were associated with BCVA below 20/200. For eyes with only inactive lesions at recruitment and BCVA measured (n = 178), 28.1% (n = 50) were blind. In these eyes, having at least one lesion larger than one disc-diameter (OR 6.30; 95% CI 2.28-22.46; p = 0.0013) and macular lesion (OR 5.69; 95% CI 2.53-13.54; p < 0.0001) were associated with BCVA below 20/200. Older age (OR 1.02; 95% CI 1.00-1.05; p = 0.0493) and active disease at presentation (OR 4.74; 95% CI 1.95-12.91; p = 0.0011) were associated with recurrences. Additional clinical attention should be directed towards patients with risk factors for poor visual outcome.
Assuntos
Cegueira/patologia , Toxoplasma/patogenicidade , Toxoplasmose/patologia , Uveíte Posterior/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Anticorpos Antiprotozoários/sangue , Antiprotozoários/uso terapêutico , Cegueira/tratamento farmacológico , Cegueira/imunologia , Cegueira/parasitologia , Brasil , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Pirimetamina/uso terapêutico , Recidiva , Retina/efeitos dos fármacos , Retina/imunologia , Retina/parasitologia , Retina/patologia , Fatores de Risco , Sulfadiazina/uso terapêutico , Toxoplasma/efeitos dos fármacos , Toxoplasma/crescimento & desenvolvimento , Toxoplasmose/tratamento farmacológico , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Uveíte Posterior/tratamento farmacológico , Uveíte Posterior/imunologia , Uveíte Posterior/parasitologia , Visão Ocular/efeitos dos fármacos , Acuidade Visual/efeitos dos fármacosRESUMO
Objective: Patients with schizophrenia have visual processing impairments. The main findings from the literature indicate that these deficits may be related to differences in paradigms, medications, and illness duration. This study is part of a large-scale study investigating visual sensitivity in schizophrenia. Here we aimed to investigate the combined effects of illness duration and antipsychotic use on contrast sensitivity function. Methods: Data were collected from 50 healthy controls and 50 outpatients with schizophrenia (classified according to illness duration and medication type) aged 20-45 years old. The contrast sensitivity function was measured for spatial frequencies ranging from 0.2 to 20 cycles per degree using linear sine-wave gratings. Results: Patients with an illness duration > 5 years had more pronounced deficits. Differences in the combined effects of illness duration and antipsychotic use were marked in patients on typical antipsychotics who had been ill > 10 years. No significant differences were found between typical and atypical antipsychotics in patients with an illness duration < 5 years. Conclusion: Visual impairment was related to both long illness duration and medication type. These results should be tested in further studies to investigate pharmacological mechanisms.
Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Transtornos da Visão/induzido quimicamente , Escalas de Graduação Psiquiátrica , Esquizofrenia/complicações , Fatores de Tempo , Visão Ocular/efeitos dos fármacos , Sensibilidades de Contraste/efeitos dos fármacos , Estudos de Casos e Controles , Clorpromazina/efeitos adversos , Resultado do Tratamento , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Patients with schizophrenia have visual processing impairments. The main findings from the literature indicate that these deficits may be related to differences in paradigms, medications, and illness duration. This study is part of a large-scale study investigating visual sensitivity in schizophrenia. Here we aimed to investigate the combined effects of illness duration and antipsychotic use on contrast sensitivity function. METHODS: Data were collected from 50 healthy controls and 50 outpatients with schizophrenia (classified according to illness duration and medication type) aged 20-45 years old. The contrast sensitivity function was measured for spatial frequencies ranging from 0.2 to 20 cycles per degree using linear sine-wave gratings. RESULTS: Patients with an illness duration > 5 years had more pronounced deficits. Differences in the combined effects of illness duration and antipsychotic use were marked in patients on typical antipsychotics who had been ill > 10 years. No significant differences were found between typical and atypical antipsychotics in patients with an illness duration < 5 years. CONCLUSION: Visual impairment was related to both long illness duration and medication type. These results should be tested in further studies to investigate pharmacological mechanisms.
Assuntos
Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Transtornos da Visão/induzido quimicamente , Adulto , Estudos de Casos e Controles , Clorpromazina/efeitos adversos , Sensibilidades de Contraste/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/complicações , Fatores de Tempo , Resultado do Tratamento , Visão Ocular/efeitos dos fármacos , Adulto JovemRESUMO
Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM) causing vision impairment even at young ages. There are numerous mechanisms involved in its development such as inflammation and cellular degeneration leading to endothelial and neural damage. These mechanisms are interlinked thus worsening the diabetic retinopathy outcome. In this review, we propose oxidative stress as the focus point of this complication onset.
Assuntos
Antioxidantes/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Estresse Oxidativo/fisiologia , Animais , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Retinopatia Diabética/metabolismo , Progressão da Doença , Humanos , Fatores de Risco , Visão Ocular/efeitos dos fármacos , Visão Ocular/fisiologiaRESUMO
PURPOSE: To investigate whether exposure to occupational levels of organic solvents in the dry cleaning industry is associated with neurotoxic symptoms and visual deficits in the perception of basic visual features such as luminance contrast and colour, higher level processing of global motion and form (Experiment 1), and cognitive function as measured in a visual search task (Experiment 2). METHODS: The Q16 neurotoxic questionnaire, a commonly used measure of neurotoxicity (by the World Health Organization), was administered to assess the neurotoxic status of a group of 33 dry cleaners exposed to occupational levels of organic solvents (OS) and 35 age-matched non dry-cleaners who had never worked in the dry cleaning industry. In Experiment 1, to assess visual function, contrast sensitivity, colour/hue discrimination (Munsell Hue 100 test), global motion and form thresholds were assessed using computerised psychophysical tests. Sensitivity to global motion or form structure was quantified by varying the pattern coherence of global dot motion (GDM) and Glass pattern (oriented dot pairs) respectively (i.e., the percentage of dots/dot pairs that contribute to the perception of global structure). In Experiment 2, a letter visual-search task was used to measure reaction times (as a function of the number of elements: 4, 8, 16, 32, 64 and 100) in both parallel and serial search conditions. RESULTS: Dry cleaners exposed to organic solvents had significantly higher scores on the Q16 compared to non dry-cleaners indicating that dry cleaners experienced more neurotoxic symptoms on average. The contrast sensitivity function for dry cleaners was significantly lower at all spatial frequencies relative to non dry-cleaners, which is consistent with previous studies. Poorer colour discrimination performance was also noted in dry cleaners than non dry-cleaners, particularly along the blue/yellow axis. In a new finding, we report that global form and motion thresholds for dry cleaners were also significantly higher and almost double than that obtained from non dry-cleaners. However, reaction time performance on both parallel and serial visual search was not different between dry cleaners and non dry-cleaners. CONCLUSIONS: Exposure to occupational levels of organic solvents is associated with neurotoxicity which is in turn associated with both low level deficits (such as the perception of contrast and discrimination of colour) and high level visual deficits such as the perception of global form and motion, but not visual search performance. The latter finding indicates that the deficits in visual function are unlikely to be due to changes in general cognitive performance.
Assuntos
Lavanderia , Exposição Ocupacional/análise , Compostos Orgânicos/toxicidade , Solventes/toxicidade , Visão Ocular/efeitos dos fármacos , Adulto , Sensibilidades de Contraste/efeitos dos fármacos , Humanos , Neurotoxinas/toxicidade , Estimulação Luminosa , Tempo de Reação/efeitos dos fármacos , Limiar Sensorial/efeitos dos fármacosRESUMO
BACKGROUND: The insecticide chlordecone was extensively used in the French West Indies to control banana root borer. Its persistence in soils has led to the widespread pollution of the environment, and human beings are still exposed to this chemical. Chlordecone has been shown to impair neurological and behavioural functions in rodents when exposed gestationally or neonatally. OBJECTIVES: The aim of the study was to evaluate the impact of prenatal and postnatal exposure to chlordecone on the cognitive, visual, and motor development of 7-month-old infants from Guadeloupe. METHODS: Infants were tested at 7 months (n=153). Visual recognition memory and processing speed were assessed with the Fagan Tests of Infant Intelligence (FTII), visual acuity with the Teller Acuity Card, and fine motor development with the Brunet-Lezine. Samples of cord blood and breast milk at 3 months (n=88) were analyzed for chlordecone concentrations. Postnatal exposure was determined through breast feeding and frequency of contaminated food consumption by the infants. RESULTS: Cord chlordecone concentrations in tertiles were associated with reduced novelty preference on the FTII in the highly exposed group (ß=-0.19, p=0.02). Postnatal exposure through contaminated food consumption was marginally related to reduced novelty preference (ß=-0.14, p=0.07), and longer processing speed (ß=0.16, p=0.07). Detectable levels of chlordecone in cord blood were associated with higher risk of obtaining low scores on the fine motor development scale (OR=1.25, p<0.01). CONCLUSION: These results suggest that pre- and postnatal low chronic exposure to chlordecone is associated with negative effects on cognitive and motor development during infancy.
Assuntos
Clordecona/toxicidade , Cognição/efeitos dos fármacos , Exposição Ambiental , Inseticidas/toxicidade , Desempenho Psicomotor/efeitos dos fármacos , Visão Ocular/efeitos dos fármacos , Guadalupe , Humanos , LactenteRESUMO
Corneal neovascularization is often accompanied by inflammatory response and loss of their immune privilege which leads to significant visual impairment and worsens the prognosis of a subsequent penetrating keratoplasty. Several types of treatment are currently used. However, there are some associated limitations and complications. The consumption of (-)-epigallocatechin 3-gallate (EGCG) has been studied extensively as a potential treatment for a variety of carcinogenic and degenerative diseases due to its ability to suppress a variety of inflammatory and angiogenic factors such as NF-κB, IL-1ß, COX2, VEGF, and matrix metalloproteinases. These factors are involved in the development of corneal neovascularization. The safety of long-term EGCG administration as well as the drug's high solubility in water urge further investigation of the therapeutic potential of this drug. Therefore, we propose that the administration of EGCG to the ocular surface represents a new chemopreventive alternative to suppress the corneal neovascularization induced by inflammation.
Assuntos
Catequina/análogos & derivados , Neovascularização da Córnea/tratamento farmacológico , Olho/metabolismo , Visão Ocular/efeitos dos fármacos , Animais , Catequina/farmacologia , Catequina/uso terapêutico , Humanos , Interleucina-1beta/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Fator de Transcrição RelARESUMO
BACKGROUND: Voriconazole is an antifungal agent with in vitro activity and clinical efficacy against yeasts, molds, and dimorphic fungi (eg, Paracoccidioides brasiliensis). The safety profile of voriconazole includes transient visual adverse events (VAEs) that resolve while undergoing treatment or after its discontinuation. OBJECTIVE: The goal of this study was to assess the long-term (ie, 6-12 months) visual safety of voriconazole in adult patients with paracoccidioidomycosis. METHODS: Ophthalmic data were prospectively collected as part of a multicenter, open-label, comparative study. Patients aged ≥18 years with paracoccidioidomycosis were randomized in a 2:1 ratio to receive either voriconazole (200 mg BID orally, after the loading dose of 400 mg BID on day 1) or itraconazole (100 mg BID orally, with no loading dose). Patients were expected to receive treatment for a minimum of 6 months, or longer if needed as determined by the investigator (maximum duration, 1 year). Visual function tests and safety assessments were performed at baseline, week 12, week 24, end of treatment (EOT), and 8 weeks post-EOT. Ophthalmic examinations included visual acuity, color vision, contrast sensitivity, visual field, funduscopy, and slit lamp biomicroscopy. Treatment compliance was monitored via pill counts at each study visit. RESULTS: Thirty-five patients (mean age, 48 years; 96.2% male; 83.0% white) were randomized to receive voriconazole and 18 to receive itraconazole. Fourteen voriconazole-treated patients received >6 months of treatment (median, 169 days). Efficacy and overall safety results have been published previously. Sixteen voriconazole-treated patients and 2 itraconazole-treated patients experienced drug-related VAEs; none was considered serious or severe or led to dose reductions or resulted in discontinuation. Overall, visual examination results were not clinically significantly different between patients treated with voriconazole or itraconazole. There was no apparent relationship between changes in visual function test results and the occurrence of VAEs in either treatment group. CONCLUSION: Clinical assessment in this study found no evidence of an effect of voriconazole on long-term visual function in these adult patients with paracoccidioidomycosis.