RESUMEN
In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones > > rods > > > ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.
Asunto(s)
Estimulación Luminosa , Células Ganglionares de la Retina , Animales , Ratas , Ratones , Masculino , Células Ganglionares de la Retina/fisiología , Femenino , Sensibilidad de Contraste/fisiología , Conducta Animal/fisiología , Células Fotorreceptoras Retinianas Conos/fisiología , Ratones Endogámicos C57BL , Percepción Visual/fisiología , Miedo/fisiología , Retina/fisiología , Vías Visuales/fisiologíaRESUMEN
Fast gamma oscillations, generated within the retina, and transmitted to the cortex via the lateral geniculate nucleus (LGN), are thought to carry information about stimulus size and continuity. This hypothesis relies mainly on studies conducted under anesthesia and the extent to which it holds under more naturalistic conditions remains unclear. Using multielectrode recordings of spiking activity in the retina and the LGN of both male and female cats, we show that visually driven gamma oscillations are absent for awake states and are highly dependent on halothane (or isoflurane). Under ketamine, responses were nonoscillatory, as in the awake condition. Response entrainment to the monitor refresh was commonly observed up to 120 Hz and was superseded by the gamma oscillatory responses induced by halothane. Given that retinal gamma oscillations are contingent on halothane anesthesia and absent in the awake cat, such oscillations should be considered artifactual, thus playing no functional role in vision.SIGNIFICANCE STATEMENT Gamma rhythms have been proposed to be a robust encoding mechanism critical for visual processing. In the retinogeniculate system of the cat, many studies have shown gamma oscillations associated with responses to static stimuli. Here, we extend these observations to dynamic stimuli. An unexpected finding was that retinal gamma responses strongly depend on halothane concentration levels and are absent in the awake cat. These results weaken the notion that gamma in the retina is relevant for vision. Notably, retinal gamma shares many of the properties of cortical gamma. In this respect, oscillations induced by halothane in the retina may serve as a valuable preparation, although artificial, for studying oscillatory dynamics.
Asunto(s)
Ritmo Gamma , Halotano , Masculino , Femenino , Animales , Retina/fisiología , Cuerpos Geniculados/fisiología , Visión Ocular , Estimulación Luminosa/métodosRESUMEN
Recent experimental work on zebrafish has shown the in vivo activity of photoreceptors and horizontal cells (HCs) as a function of the stimulus spectrum, highlighting the appearance of chromatic-opponent signals at their first synaptic connection. Altogether with the observed lack of excitatory intercone connections, these findings suggest that the mechanism yielding early color opponency in zebrafish is dominated by inhibitory feedback. We propose a neuronal population model based on zebrafish retinal circuitry to investigate whether networks with predominantly inhibitory feedback are more advantageous in encoding chromatic information than networks with mixed excitatory and inhibitory mechanisms. We show that networks with dominant inhibitory feedback exhibit a unique and reliable encoding of chromatic information. In contrast, this property is not guaranteed in networks with strong excitatory intercone connections, exhibiting bistability. These findings provide a theoretical explanation for the absence of excitatory intercone couplings in zebrafish color circuits. In addition, our study shows that these networks, with only one type of horizontal cell, are suitable to encode most of the variance from the zebrafish environment. However, at least two successive layers of inhibitory neurons are needed to reach the optimum. Finally, we contrast the encoding performance of networks with different opsin sensitivities, showing an improvement of only 13% compared with zebrafish, suggesting that the zebrafish retina is adapted to encode color information from its habitat efficiently.
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Retina , Pez Cebra , Animales , Retina/fisiología , Células Fotorreceptoras , Neuronas , Percepción de Color/fisiologíaRESUMEN
The retina hosts all processes needed to convert external visual stimuli into a neural code. Light phototransduction and its conversion into an electrical signal involve biochemical cascades, ionic regulations, and different kinds of coupling, among other relevant processes. These create a nonlinear processing scheme and light-dependent adaptive responses. The dynamical adaptation model formulated in recent years is an excellent phenomenological candidate to resume all these phenomena into a single feedforward processing scheme. In this work, we analyze this description in highly nonlinear conditions and find that responses do not match those resulting from a very detailed microscopic model, developed to reproduce electrophysiological recordings on horizontal cells. When a delayed light-dependent gain factor incorporates into the description, responses are in excellent agreement, even when spanning several orders of magnitude in light intensity, contrast, and duration, for simple and complex stimuli. This extended model may be instrumental for studies of the retinal function, enabling the linking of the microscopic domain to the understanding of signal processing properties, and further incorporated in spatially extended retinal networks.
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Luz , Retina , Retina/fisiología , Adaptación Fisiológica/fisiología , NeuronasRESUMEN
ABSTRACT Purpose: To describe an innovative animal model of eye transplantation used in rabbits. Methods: six Dutch-belted male rabbits were submitted to lateral orbitotomy in the right eye, wide retrobulbar anatomy exposure, dissection of the structures, identification and distal section of the optic nerve followed by anastomosis either by vicryl (group 1) or fibrin glue (group 2). Electroretinography recording was performed before the section of the optic nerve and every 30 seconds after, to monitor the function of retina. Left eye was used as control group. Results: After optic nerve resection and anastomosis, stable ERG amplitude of the right eye was lost after 302 seconds in group 1 and after 296 seconds on group 2. Left eye kept longer stable ERG amplitude curves. Conclusions: The animal model of whole eye transplantation was effective in describing a novel technique to be used in rabbits, with success of the anatomic procedure. Further studies will clarify the best anastomosis methods and maintenance of function of the receptor organ. Translational relevance: this animal model of whole eye transplantation provides a novel perspective for blind patients and the research models, since we describe a novel mammal animal model. This model can be used as basis of a human model of whole eye transplantation in future studies.
RESUMO Objetivo: Descrever uma técnica cirúrgica inovadora para transplante de olho em um modelo animal em coelhos. Métodos: Seis coelhos machos com Dutch Belted foram submetidos à orbitotomia lateral do olho direito, com ampla exposição da anatomia retrobulbar, dissecção do cone muscular, exposição e secção distal do nervo óptico seguida de anastomose por vicryl (Grupo 1) ou cola de fibrina (Grupo 2). O registro da eletrorretinografia foi realizado antes da secção do nervo óptico e a cada 30 segundos após, para monitorar a função da retina. O olho esquerdo foi usado como grupo controle. Resultados: Após a ressecção do nervo óptico, a estabilidade da amplitude da eletrorretinografia foi perdida no olho direito após 302 segundos no Grupo 1 e após 296 segundos no Grupo 2. O olho esquerdo manteve eletrorretinografia estável por períodos mais longos. Conclusão: O modelo animal de transplante total de olho foi eficaz em descrever uma nova técnica cirúrgica para ser utilizada em laboratório com coelhos, com sucesso do procedimento anatômico. Novos estudos esclarecerão os melhores métodos de anastomose e manutenção da função do órgão receptor.
Asunto(s)
Animales , Masculino , Nervio Óptico/cirugía , Retina/fisiología , Electrorretinografía , Ojo/trasplante , Órbita/cirugía , Conejos , Células Ganglionares de la Retina/fisiología , Anastomosis Quirúrgica , Enucleación del Ojo , Modelos Animales , Microscopía con Lámpara de HendiduraRESUMEN
Since the discovery of melanopsin as a retinal non-visual photopigment, opsins have been described in several organs and cells. This distribution is strikingly different from the classical localization of photopigments in light-exposed tissues such as the eyes and the skin. More than 10 years ago, a new paradigm in the field was created as opsins were shown, to detect not only light, but also thermal energy in Drosophila. In agreement with these findings, thermal detection by opsins was also reported in mammalian cells. Considering the presence of opsins in tissues not reached by light, an intriguing question has emerged: What is the role of a classical light-sensor, and more recently appreciated thermo-sensor, in these tissues? To tackle this question, we address in this review the most recent studies in the field, with emphasis in mammals. We provide the present view about the role of opsins in peripheral tissues, aiming to integrate the current knowledge of the presence and function of opsins in organs that are not directly affected by light.
Asunto(s)
Luz , Opsinas/metabolismo , Retina/fisiologíaRESUMEN
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.
Asunto(s)
Visión de Colores/fisiología , Electrorretinografía/métodos , Retina/fisiología , Adolescente , Adulto , Femenino , Voluntarios Sanos , Humanos , Masculino , Microelectrodos , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estimulación Luminosa , Valores de Referencia , Células Ganglionares de la Retina/fisiología , Adulto JovenRESUMEN
Oxidative stress is implicated in retinal cell injury associated with glaucoma and other retinal diseases. However, the mechanism by which oxidative stress leads to retinal damage is not completely understood. Transient receptor potential ankyrin 1 (TRPA1) is a redox-sensitive channel that, by amplifying the oxidative stress signal, promotes inflammation and tissue injury. Here, we investigated the role of TRPA1 in retinal damage evoked by ischemia (1 hour) and reperfusion (I/R) in mice. In wild-type mice, retinal cell numbers and thickness were reduced at both day-2 and day-7 after I/R. By contrast, mice with genetic deletion of TRPA1 were protected from the damage seen in their wild-type littermates. Daily instillation of eye drops containing two different TRPA1 antagonists, an oxidative stress scavenger, or a NADPH oxidase-1 inhibitor also protected the retinas of C57BL/6J mice exposed to I/R. Mice with genetic deletion of the proinflammatory TRP channels, vanilloid 1 (TRPV1) or vanilloid 4 (TRPV4), were not protected from I/R damage. Surprisingly, genetic deletion or pharmacological blockade of TRPA1 also attenuated the increase in the number of infiltrating macrophages and in the levels of the oxidative stress biomarker, 4-hydroxynonenal, and of the apoptosis biomarker, active caspase-3, evoked by I/R. These findings suggest that TRPA1 mediates the oxidative stress burden and inflammation that result in murine retinal cell death. We also found that TRPA1 (both mRNA and protein) is expressed by human retinal cells. Thus, it is possible that inhibition of a TRPA1-dependent pathway could also attenuate glaucoma-related retinal damage.
Asunto(s)
Daño por Reperfusión/metabolismo , Retina/metabolismo , Canal Catiónico TRPA1/metabolismo , Animales , Muerte Celular , Inflamación , Isquemia , Masculino , Ratones , Ratones Endogámicos C57BL , NADPH Oxidasa 1/metabolismo , Estrés Oxidativo/fisiología , Reperfusión , Daño por Reperfusión/fisiopatología , Retina/fisiología , Enfermedades de la Retina , Canal Catiónico TRPA1/genética , Canal Catiónico TRPA1/fisiología , Canales Catiónicos TRPV/metabolismo , Canales de Potencial de Receptor Transitorio/genéticaRESUMEN
Motion detection represents one of the critical tasks of the visual system and has motivated a large body of research. However, it remains unclear precisely why the response of retinal ganglion cells (RGCs) to simple artificial stimuli does not predict their response to complex, naturalistic stimuli. To explore this topic, we use Motion Clouds (MC), which are synthetic textures that preserve properties of natural images and are merely parameterized, in particular by modulating the spatiotemporal spectrum complexity of the stimulus by adjusting the frequency bandwidths. By stimulating the retina of the diurnal rodent, Octodon degus with MC we show that the RGCs respond to increasingly complex stimuli by narrowing their adjustment curves in response to movement. At the level of the population, complex stimuli produce a sparser code while preserving movement information; therefore, the stimuli are encoded more efficiently. Interestingly, these properties were observed throughout different populations of RGCs. Thus, our results reveal that the response at the level of RGCs is modulated by the naturalness of the stimulus - in particular for motion - which suggests that the tuning to the statistics of natural images already emerges at the level of the retina.
Asunto(s)
Ritmo Circadiano/fisiología , Percepción de Movimiento/fisiología , Movimiento (Física) , Octodon/fisiología , Retina/fisiología , Células Ganglionares de la Retina/fisiología , Algoritmos , Animales , Potenciales Postsinápticos Inhibidores/fisiología , Modelos Neurológicos , Movimiento/fisiología , Red Nerviosa/fisiología , Estimulación Luminosa/métodos , Retina/citología , Transmisión Sináptica/fisiologíaRESUMEN
PURPOSE: To evaluate the 52-week safety and efficacy of intravitreal ziv-aflibercept in patients with neovascular age-related macular degeneration. METHODS: All patients received three monthly intravitreal injections of 0.05 mL of ziv-aflibercept (1.25 mg) followed by a pro re nata regimen. The best-corrected visual acuity and spectral domain optical coherence tomography were obtained at baseline and monthly. Full-field and multifocal electroretinograms were obtained at baseline and 4, 13, 26, and 52 weeks. For some full-field electroretinography parameters, we calculated the differences between baseline and 52 weeks and then compared those differences between treated and untreated fellow eyes. RESULTS: Fifteen patients were included and 14 completed the 52-week follow-up. The mean best-corrected visual acuity improved from 0.95 ± 0.41 (20/200) at baseline to 0.75 ± 0.51 (20/125) logarithm of the minimum angle of resolution at 52 weeks (P = 0.0066). The baseline central retinal thickness decreased from 478.21 ± 153.48 µm to 304.43 ± 98.59 µm (P = 0.0004) at 52 weeks. Full-field electroretinography parameters used to assess retinal toxicity after intravitreal injections (rod response and oscillatory potentials) remained unchanged during follow-up. The average multifocal electroretinography macular response in 5° showed increased N1-P1 amplitude and decreased P1 implicit time (P < 0.05). One patient presented with intraocular inflammation after the seventh intravitreal procedure. CONCLUSION: The results suggested that intravitreal ziv-aflibercept might be safe and effective for treating neovascular age-related macular degeneration. More patients and a longer follow-up are needed to confirm the long-term outcomes of intravitreal ziv-aflibercept.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neovascularización Coroidal/tratamiento farmacológico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Degeneración Macular Húmeda/tratamiento farmacológico , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/fisiopatología , Electrorretinografía , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes de Fusión/efectos adversos , Retina/fisiología , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/fisiología , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/fisiopatologíaRESUMEN
We studied the time course of changes of cytochrome oxidase (CytOx) blob spatial density and blob cross-sectional area of deprived (D) and nondeprived (ND) portions of V1 in four capuchin monkeys after massive and restricted retinal laser lesions. Laser shots at the border of the optic disc produced massive retinal lesions, while low power laser shots in the retina produced restricted retinal lesions. These massive and restricted retinal lesions were intended to simulate glaucoma and diabetic retinopathy, respectively. We used a Neodymium-YAG dual frequency laser to make the lesions. We measured Layer III blobs in CytOx-reacted tangential sections of flat-mounted preparations of V1. The plasticity of the blob system and that of the ocular dominance columns (ODC) varied with the degree of retinal lesions. We found that changes in the blob system were different from that of the ODC. Blob sizes changed drastically in the region corresponding to the retinal lesion. Blobs were larger and subjectively darker above and below the non deprived ODC than in the deprived columns. With restricted lesions, blobs corresponding to the ND columns had sizes similar to those from non-lesioned areas. In contrast, blobs corresponding to the deprived columns were smaller than those from nonlesioned areas. With massive lesions, ND blobs were larger than the deprived blobs. Plastic changes in blobs described here occur much earlier than previously described.
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Complejo IV de Transporte de Electrones/análisis , Terapia por Láser/efectos adversos , Plasticidad Neuronal/fisiología , Retina/fisiología , Corteza Visual/fisiología , Animales , Haplorrinos , Terapia por Láser/métodos , Neodimio/toxicidad , Retina/química , Retina/lesiones , Sapajus apella , Corteza Visual/química , Corteza Visual/citologíaRESUMEN
Cell adhesion molecules play a central role in morphogenesis, as they mediate the complex range of interactions between different cell types that result in their arrangement in multicellular organs and tissues. How their coordinated dynamic expression in space and time - an essential requirement for their function - is regulated at the genomic and transcriptional levels constitutes an important, albeit still little understood question. The Irre Cell Recognition Module (IRM) is a highly conserved phylogenetically group of structurally related single pass transmembrane glycoproteins belonging to the immunoglobulin superfamily that in Drosophila melanogaster are encoded by the genes roughest (rst), kin-of-irre (kirre), sticks-and-stones (sns) and hibris (hbs). Their cooperative and often partly redundant action are crucial to major developmental processes such axonal pathfinding, myoblast fusion and patterning of the pupal retina. In this latter system rst and kirre display a tightly regulated complementary transcriptional pattern so that lowering rst mRNA levels leads to a concomitant increase in kirre mRNA concentration. Here we investigated whether other IRM components are similarly co-regulated and the extent changes in their mRNA levels affect each other as well as their collective function in retinal patterning. Our results demonstrate that silencing any of the four IRM genes in 24% APF retinae changes the levels all other group members although only kirre and hbs mRNA levels are increased. Furthermore, expression, in a rst null background, of truncated versions of rst cDNA in which the portion encoding the intracellular domain has been partially or completely removed not only can still induce changes in mRNA levels of other IRM members but also result in Kirre mislocalization. Taken together, our data point to the presence of a highly precise and fine-tuned control mechanism coordinating IRM expression that may be crucial to the functional redundancy shown by its components during the patterning of the pupal retina.
Asunto(s)
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas del Ojo/genética , Pupa/genética , Retina/fisiología , Transcripción Genética/genética , Animales , Moléculas de Adhesión Celular/genética , Regulación de la Expresión Génica/genética , Glicoproteínas/genética , Proteínas de la Membrana/genética , Morfogénesis/genética , ARN Mensajero/genéticaRESUMEN
Neuronal activity in the retina generates osmotic gradients that lead to Müller cell swelling, followed by a regulatory volume decrease (RVD) response, partially due to the isoosmotic efflux of KCl and water. However, our previous studies in a human Müller cell line (MIO-M1) demonstrated that an important fraction of RVD may also involve the efflux of organic solutes. We also showed that RVD depends on the swelling-induced Ca2+ release from intracellular stores. Here we investigate the contribution of taurine (Tau) and glutamate (Glu), the most relevant amino acids in Müller cells, to RVD through the volume-regulated anion channel (VRAC), as well as their Ca2+ dependency in MIO-M1 cells. Swelling-induced [3H]Tau/[3H]Glu release was assessed by radiotracer assays and cell volume by fluorescence videomicroscopy. Results showed that cells exhibited an osmosensitive efflux of [3H]Tau and [3H]Glu (Tau > Glu) blunted by VRAC inhibitors 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)-oxybutyric acid and carbenoxolone reducing RVD. Only [3H]Tau efflux was mainly dependent on Ca2+ release from intracellular stores. RVD was unaffected in a Ca2+-free medium, probably due to Ca2+-independent Tau and Glu release, but was reduced by chelating intracellular Ca2+. The inhibition of phosphatidylinositol-3-kinase reduced [3H]Glu efflux but also the Ca2+-insensitive [3H]Tau fraction and decreased RVD, providing evidence of the relevance of this Ca2+-independent pathway. We propose that VRAC-mediated Tau and Glu release has a relevant role in RVD in Müller cells. The observed disparities in Ca2+ influence on amino acid release suggest the presence of VRAC isoforms that may differ in substrate selectivity and regulatory mechanisms, with important implications for retinal physiology. NEW & NOTEWORTHY The mechanisms for cell volume regulation in retinal Müller cells are still unknown. We show that swelling-induced taurine and glutamate release mediated by the volume-regulated anion channel (VRAC) largely contributes the to the regulatory volume decrease response in a human Müller cell line. Interestingly, the hypotonic-induced efflux of these amino acids exhibits disparities in Ca2+-dependent and -independent regulatory mechanisms, which strongly suggests that Müller cells may express different VRAC heteromers formed by the recently discovered leucine-rich repeat containing 8 (LRRC8) proteins.
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Calcio/metabolismo , Tamaño de la Célula , Células Ependimogliales/citología , Células Ependimogliales/metabolismo , Ácido Glutámico/metabolismo , Taurina/metabolismo , Análisis de Varianza , Aniones/metabolismo , Antiulcerosos/farmacología , Carbenoxolona/farmacología , Ciclopentanos/farmacología , Humanos , Indanos/farmacología , Canales Iónicos/antagonistas & inhibidores , Microscopía por Video , Osmorregulación/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Retina/fisiologíaRESUMEN
A Newman-Watts graph is formed by including random links in a regular lattice. Here, the emergence of synchronization in coupled Newman-Watts graphs is studied. The whole neural network is considered as a toy model of mammalian visual pathways. It is composed by four coupled graphs, in which a coupled pair represents the lateral geniculate nucleus and the visual cortex of a cerebral hemisphere. The hemispheres communicate with each other through a coupling between the graphs representing the visual cortices. This coupling makes the role of the corpus callosum. The state transition of neurons, supposed to be the nodes of the graphs, occurs in discrete time and it follows a set of deterministic rules. From periodic stimuli coming from the retina, the neuronal activity of the whole network is numerically computed. The goal is to find out how the values of the parameters related to the network topology affect the synchronization among the four graphs.
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Cuerpo Calloso/fisiología , Cuerpos Geniculados/fisiología , Modelos Neurológicos , Retina/fisiología , Corteza Visual/fisiología , Animales , Simulación por Computador , Sincronización Cortical , Mamíferos , Neuronas/fisiología , Factores de Tiempo , Vías Visuales/fisiología , Percepción Visual/fisiologíaRESUMEN
BACKGROUND: Pigmented and albino rabbits are commonly used in visual research; however, the lack of pigment in the eyes may affect retinal responses. Here, we compare and describe the differences of retinal function between pigmented (English Butterfly) and albino (New Zealand) rabbits. METHODS: Electroretinograms were recorded in pigmented and albino rabbits in the dark-adapted eye, in the light-adapted eye and for four temporal frequencies in the light-adapted eye. The implicit time and amplitude of the a- and b-waves were analyzed, as well as the amplitude and phase of the first harmonic component of the photopic flicker response. RESULTS: Albino rabbits presented significantly larger amplitudes for both a- and b-waves at all intensities and frequencies. The intensity-response function of the scotopic b-wave also showed that the albino retina is more sensitive than the pigmented retina and the larger flicker amplitudes found in the albino group also revealed post-receptoral changes specifically related to cone pathways. CONCLUSIONS: The larger amplitude of albino receptoral and post-receptoral activities might be attributed to greater availability of light due to scatter and reflection at the retinal layer, and as the differences in response amplitudes between the groups increase with flicker frequency, we suggest that ON bipolar cells recover faster in the albino group, suggesting that this might be a mechanism to explain the higher temporal resolution for albinos compared to the pigmented group.
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Albinismo Oculocutáneo/fisiopatología , Electrorretinografía , Conejos/fisiología , Retina/fisiología , Animales , Visión de Colores/fisiología , Adaptación a la Oscuridad , Visión Nocturna/fisiología , Estimulación Luminosa , Células Fotorreceptoras Retinianas Conos/fisiología , Pigmentación de la PielRESUMEN
A17 amacrine cells are an important part of the scotopic pathway. Their synaptic varicosities receive glutamatergic inputs from rod bipolar cells (RBC) and release GABA onto the same RBC terminal, forming a reciprocal feedback that shapes RBC depolarization. Here, using patch-clamp recordings, we characterized electrical coupling between A17 cells of the rat retina and report the presence of strongly interconnected and non-coupled A17 cells. In coupled A17 cells, evoked currents preferentially flow out of the cell through GJs and cross-synchronization of presynaptic signals in a pair of A17 cells is correlated to their coupling degree. Moreover, we demonstrate that stimulation of one A17 cell can induce electrical and calcium transients in neighboring A17 cells, thus confirming a functional flow of information through electrical synapses in the A17 coupled network. Finally, blocking GJs caused a strong decrease in the amplitude of the inhibitory feedback onto RBCs. We therefore propose that electrical coupling between A17 cells enhances feedback onto RBCs by synchronizing and facilitating GABA release from inhibitory varicosities surrounding each RBC axon terminal. GJs between A17 cells are therefore critical in shaping the visual flow through the scotopic pathway.
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Células Amacrinas/fisiología , Células Bipolares de la Retina/metabolismo , Animales , Calcio/metabolismo , Adaptación a la Oscuridad/fisiología , Retroalimentación , Femenino , Uniones Comunicantes/fisiología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Visión Nocturna/fisiología , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley , Receptores AMPA/metabolismo , Receptores de GABA/metabolismo , Retina/metabolismo , Retina/fisiología , Células Bipolares de la Retina/fisiología , Células Fotorreceptoras Retinianas Bastones/fisiología , Sinapsis/metabolismo , Transmisión Sináptica/fisiología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
OBJECTIVE: to determine the functional and morphological effects at rabbits retina of PS80 concentration used in the preparation of intravitreal drugs. METHODS: eleven New Zealand rabbits received a intravitreal injection of 0.1ml of PS80. As control, the contralateral eye of each rabbit received the same volume of saline. Electroretinography was performed according to a modified protocol, as well as biomicroscopy and retina mapping before injection and seven and ten days after. Animals were euthanized in the 30th day and the retinas were analyzed by light microscopy. RESULTS: eyes injected with PS80 did not present clinical signs of intraocular inflammation. Electroretinography did not show any alteration of extent and implicit time of a and b waves at scotopic and photopic conditions. There were no morphological alterations of retinas at light microscopy. CONCLUSION: intravitreal injection of PS80 in the used concentration for intravitreal drug preparations do not cause any functional or morphological alterations of rabbit retinas. These results suggest that PS80 is not toxic to rabbit retinas and may be safely used in the preparation of new lipophilic drugs for intravitreal injection.
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Polisorbatos/administración & dosificación , Retina/anatomía & histología , Retina/fisiología , Animales , Electrorretinografía , Inyecciones Intravítreas , Conejos , Retina/efectos de los fármacosRESUMEN
ABSTRACT Objective : to determine the functional and morphological effects at rabbits retina of PS80 concentration used in the preparation of intravitreal drugs. Methods: eleven New Zealand rabbits received a intravitreal injection of 0.1ml of PS80. As control, the contralateral eye of each rabbit received the same volume of saline. Electroretinography was performed according to a modified protocol, as well as biomicroscopy and retina mapping before injection and seven and ten days after. Animals were euthanized in the 30th day and the retinas were analyzed by light microscopy. Results: eyes injected with PS80 did not present clinical signs of intraocular inflammation. Electroretinography did not show any alteration of extent and implicit time of a and b waves at scotopic and photopic conditions. There were no morphological alterations of retinas at light microscopy. Conclusion: intravitreal injection of PS80 in the used concentration for intravitreal drug preparations do not cause any functional or morphological alterations of rabbit retinas. These results suggest that PS80 is not toxic to rabbit retinas and may be safely used in the preparation of new lipophilic drugs for intravitreal injection.
RESUMO Objetivo: determinar os efeitos funcionais e morfológicos na retina de coelhos da concentração de PS80 utilizada na preparação de drogas intravítreas. Métodos: onze coelhos New Zealand receberam injeção intravítrea de 0,1ml de PS80. Como controle, o olho contralateral de cada coelho recebeu o mesmo volume de soro fisiológico. Foram realizados eletrorretinogramas de acordo com o protocolo modificado, biomicroscopia e mapeamento de retina antes da injeção, sete e dez dias depois. Os animais foram sacrificados no 30o dia e as retinas analisadas por microscopia de luz. Resultados: os olhos injetados com PS80 não apresentaram sinais clínicos de inflamação intraocular. O eletrorretinograma não apresentou alteração de amplitude e tempo implícito das ondas a e b nas condições escotópica e fotópica. Não houve alteração morfológica da retina na microscopia de luz. Conclusão: a injeção intravítrea de PS80 na concentração utilizada na preparação de drogas intravítreas não causa alterações funcionais e morfológicas na retina de coelhos. Esses resultados sugerem que o PS80 não é tóxico para a retina de coelhos e pode ser usado com segurança na preparação de novas drogas lipofílicas para injeção intravítrea.
Asunto(s)
Animales , Polisorbatos/administración & dosificación , Retina/anatomía & histología , Retina/fisiología , Conejos , Retina/efectos de los fármacos , Electrorretinografía , Inyecciones IntravítreasRESUMEN
Purpose: To analyze the presence of complex alleles of the ABCA4 gene in Brazilian patients with Stargardt disease and to assess the correlation with clinical features. Methods: This was an observational cross-sectional study. Patients with a diagnosis of Stargardt disease who presented three pathogenic variants of the ABCA4 gene or who had variants previously described as complex alleles were included. The relatives of these probands were evaluated in the segregation analysis. The patients were evaluated based on age at symptom onset and visual acuity, and the clinical characteristics were classified according to the findings observed on autofluorescence examination. Results: Among the 47 families analyzed, approximately 30% (14/47) presented complex alleles. The segregation analysis in 14 families with cases of Stargardt disease identified three novel complex alleles and one previously described complex allele. The known complex allele p.[Leu541Pro; Ala1038Val] was identified in two families. The novel complex alleles identified were p.[Leu541Pro; Arg1443His] in five families, p.[Ser1642Arg; Val1682_Val1686del] in seven families, and p.[Pro1761Arg; Arg2106Cys] in one family. Furthermore, four new variants (p.Lys22Asn, p.Asp915Asn, p.Glu1447Val, and p.Pro1761Arg) were identified in the second allele of the ABCA4 gene. Conclusions: Segregation analysis is important in order to confirm the molecular diagnosis of patients with Stargardt disease, given the frequency of complex alleles in the ABCA4 gene. The various pathogenic variation combinations observed in this study were associated with different phenotypes.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Alelos , Degeneración Macular/congénito , Mutación , Adolescente , Adulto , Anciano , Brasil , Niño , Estudios Transversales , Análisis Mutacional de ADN , Electrorretinografía , Femenino , Estudios de Asociación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Degeneración Macular/diagnóstico , Degeneración Macular/genética , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Linaje , Retina/fisiología , Enfermedad de Stargardt , Agudeza Visual/fisiología , Adulto JovenRESUMEN
Damage in fish activates retina repair that restores sight. The purinergic signalling system serves multiple homeostatic functions and has been implicated in cell cycle control of progenitor cells in the developing retina. We examined whether changes in the expression of purinergic molecules were instrumental in the proliferative phase after injury of adult zebrafish retinas with ouabain. P2RY1 messenger RNA (mRNA) increased early after injury and showed maximal levels at the time of peak progenitor cell proliferation. Extracellular nucleotides, mainly ADP, regulate P2RY1 transcriptional and protein expression. The injury-induced upregulation of P2RY1 is mediated by an autoregulated mechanism. After injury, the transcriptional expression of ecto-nucleotidases and ecto-ATPases also increased and ecto-ATPase activity inhibitors decreased Müller glia-derived progenitor cell amplification. Inhibition of P2RY1 endogenous activation prevented progenitor cell proliferation at two intervals after injury: one in which progenitor Müller glia mitotically activates and the second one in which Müller glia-derived progenitor cells amplify. ADPßS induced the expression of lin28a and ascl1a genes in mature regions of uninjured retinas. The expression of these genes, which regulate multipotent Müller glia reprogramming, was significantly inhibited by blocking the endogenous activation of P2RY1 early after injury. We consistently observed that the number of glial fibrillary acidic protein-BrdU-positive Müller cells after injury was larger in the absence than in the presence of the P2RY1 antagonist. Ecto-ATPase activity inhibitors or P2RY1-specific antagonists did not modify apoptotic cell death at the time of peak progenitor cell proliferation. The results suggested that ouabain injury upregulates specific purinergic signals which stimulates multipotent progenitor cell response.