RESUMO
Elevation of mean intraocular pressure (IOP) has long been recognized as a leading risk factor for glaucoma. Less is known about the possible contribution of moment-to-moment variations in IOP to disease development and progression due to limitations of tonometry, the prevailing method of IOP measurement. Tonometry provides good estimates of mean IOP but not IOP variance. The aim of this study was to quantitatively characterize IOP variability via round-the-clock IOP telemetry in conscious unrestrained rats. The anterior chamber of one eye was implanted with a microcannula connected to a wireless backpack telemetry system, and IOP data were collected every 4 s for one week. The cannula was then repositioned under the conjunctiva, and control data were collected for an additional week. IOP statistics were computed in 30-min intervals over a 24-h period and averaged across days. All animals exhibited a diurnal variation in mean IOP, while deviations about the mean were independent of time of day. Correlation analysis of the deviations revealed transient and sustained components, which were respectively extracted from IOP records using an event detection algorithm. The amplitude and interval distributions of transient and sustained events were characterized, and their energy content was estimated based on outflow tissue resistance of rat eyes. Transient IOP events occurred â¼231 times per day and were typically ≤5 mmHg in amplitude and 2-8 min in duration, while sustained IOP events occurred â¼16 times per day and were typically ≤5 mmHg in amplitude and 20-60 min in duration. Both persisted but were greatly reduced in control recordings, implying minor contamination of IOP data by motion-induced telemetry noise. Sustained events were also often synchronous across implanted animals, indicating that they were driven by autonomic startle and stress responses or other physiological processes activated by sensory signals in the animal housing environment. Not surprisingly, the total daily fluidic energy applied to resistive outflow pathways was determined primarily by basal IOP level. Nevertheless, transient and sustained fluctuations collectively contributed 6% and diurnal fluctuations contributed 9% to daily IOP energy. It is therefore important to consider the cumulative impact of biomechanical stress that IOP fluctuations apply over time to ocular tissues.
Assuntos
Glaucoma , Pressão Intraocular , Ratos , Animais , Tonometria Ocular , Ritmo Circadiano/fisiologia , TelemetriaRESUMO
Intraocular pressure (IOP) is important for eye health as abnormal levels can led to ocular tissue damage. IOP is typically estimated by tonometry, which only provides snapshots of pressure history. Tonometry also requires subject cooperation and corneal contact that may influence IOP readings. The aim of this research was to investigate IOP dynamics of conscious animals in response to stressors, common anesthetics, tonometry, and temperature manipulations. An eye of male Brown-Norway rats was implanted with a fluid-filled cannula connected to a wireless telemetry system that records IOP continuously. Stress effects were examined by restricting animal movements. Anesthetic effects were examined by varying isoflurane concentration or injecting a bolus of ketamine. Tonometry effects were examined using applanation and rebound tonometers. Temperature effects were examined by exposing anesthetized and conscious animals to warm or cool surfaces. Telemetry recordings revealed that IOP fluctuates spontaneously by several mmHg, even in idle and anesthetized animals. Environmental disturbances also caused transient IOP fluctuations that were synchronous in recorded animals and could last over a half hour. Animal immobilization produced a rapid sustained elevation of IOP that was blocked by anesthetics, whereas little-to-no IOP change was detected in isoflurane- or ketamine-anesthetized animals if body temperature (BT) was maintained. IOP and BT decreased precipitously when heat support was not provided and were highly correlated during surface temperature manipulations. Surface temperature had no impact on IOP of conscious animals. IOP increased slightly during applanation tonometry but not rebound tonometry. The results show that IOP is dynamically modulated by internal and external factors that can activate rapidly and last long beyond the initiating event. Wireless telemetry indicates that animal interaction induces startle and stress responses that raise IOP. Anesthesia blocks these responses, which allows for better tonometry estimates of resting IOP provided that BT is controlled.
Assuntos
Anestésicos Gerais/administração & dosagem , Temperatura Corporal/fisiologia , Pressão Intraocular/fisiologia , Estresse Fisiológico , Tonometria Ocular , Doença Aguda , Anestésicos Dissociativos/administração & dosagem , Anestésicos Inalatórios/administração & dosagem , Animais , Isoflurano/administração & dosagem , Ketamina/administração & dosagem , Masculino , Ratos , Ratos Endogâmicos BN , TelemetriaRESUMO
KEY POINTS: An elevation in intracranial pressure (ICP) lowers conventional outflow facility (increases aqueous outflow resistance) of rat eyes. The reduction in outflow facility correlates with an increase in intraocular pressure (IOP). The effect of ICP elevation on outflow facility and IOP is blocked by TTX. The results indicate that aqueous humour dynamics is modulated by ICP-driven neural feedback from the brain. This feedback mechanism may act to stabilize translaminar pressure across the optic nerve head and may provide a new avenue for glaucoma therapy. ABSTRACT: While intraocular pressure (IOP) is a well-known risk factor for glaucoma, intracranial pressure (ICP) is attracting heightened interest because of its influence on optic nerve head biomechanics. Studies have shown that ICP can have marked impacts on posterior eye health by modifying the translaminar pressure gradient across the optic nerve. There is also growing evidence that IOP and ICP may be interconnected, although the mechanism of their putative interaction is unknown. We sought to test the hypothesis that ICP modulates IOP by altering aqueous humour dynamics. The anterior chamber and lateral ventricle of anaesthetized Brown-Norway rats were cannulated with fine-gauge needles connected to a programmable pump and saline reservoir, respectively. ICP was manipulated by varying reservoir height, and eye outflow facility (C) was determined from the pump flow rate required to hold IOP at different levels. C was 22 ± 4 nl/min/mmHg at resting ICP and 13 ± 3 nl/min/mmHg when ICP was raised 15 mmHg, a reduction of 41 ± 13% (n = 18). The decrease in outflow facility was independent of blood pressure, reversible, scaled with ICP elevation and correlated with increases in resting IOP. It was physiological in origin because C returned to baseline values after the rats were killed and corneal application of TTX though ICP remained elevated. These results indicate that a neural feedback mechanism driven by ICP regulates conventional outflow facility in rats. The mechanism may protect the eye from translaminar pressure swings and may offer a new target for glaucoma treatment.
Assuntos
Humor Aquoso , Glaucoma/fisiopatologia , Pressão Intracraniana , Pressão Intraocular , Animais , Nervo Óptico , RatosRESUMO
Repeated spike firing can transmit information at synapses and modulate spike timing, shape, and conduction velocity. These latter effects have been found to result from voltage-induced changes in ion currents and could alter the signals carried by axons. Here, we test whether Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates spike propagation in adult rat optic nerve. We find that small-, medium-, and large-diameter axons bind anti-Thr286-phosphorylated CaMKII (pT286) antibodies and that, in isolated optic nerves, electrical stimulation reduces pT286 levels, spike propagation is hastened by CaMKII autophosphorylation and slowed by CaMKII dephosphorylation, single and multiple spikes slow propagation of subsequently activated spikes, and more frequent stimulation produces greater slowing. Likewise, exposing freely moving animals to flickering illumination reduces pT286 levels in optic nerves and electrically eliciting spikes in vivo in either the optic nerve or optic chiasm slows subsequent spike propagation in the optic nerve. By increasing the time that elapses between successive spikes as they propagate, pT286 dephosphorylation and activity-induced spike slowing reduce the frequency of propagated spikes below the frequency at which they were elicited and would thus limit the frequency at which axons synaptically drive target neurons. Consistent with this, the ability of retinal ganglion cells to drive at least some lateral geniculate neurons has been found to increase when presented with light flashes at low and moderate temporal frequencies but less so at high frequencies. Activity-induced decreases in spike frequency may also reduce the energy required to maintain normal intracellular Na+ and Ca2+ levels.SIGNIFICANCE STATEMENT By propagating along axons at constant velocities, spikes could drive synapses as frequently as they are initiated. However, the onset of spiking has been found to alter the conduction velocity of subsequent ("follower") spikes in various preparations. Here, we find that spikes reduce spike frequency in rat optic nerve by slowing follower spike propagation and that electrically stimulated spiking ex vivo and spike-generating flickering illumination in vivo produce net decreases in axonal Ca2+/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation. Consistent with these effects, propagation speed increases and decreases, respectively, with CaMKII autophosphorylation and dephosphorylation. Lowering spike frequency by CaMKII dephosphorylation is a novel consequence of axonal spiking and light adaptation that could decrease synaptic gain as stimulus frequency increases and may also reduce energy use.
Assuntos
Potenciais de Ação/fisiologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Condução Nervosa/fisiologia , Nervo Óptico/fisiologia , Animais , Estimulação Elétrica , Feminino , Masculino , Neurônios/fisiologia , Nervo Óptico/metabolismo , Fosforilação , Ratos , Ratos Long-Evans , Sinapses/fisiologiaRESUMO
PURPOSE: The existence of retinopetal (sometimes referred to as "efferent" or "centrifugal") axons in the mammalian optic nerve is a topic of long-standing debate. Opposition is fading as efferent innervation of the retina has now been widely documented in rodents and other animals. The existence and function of an efferent system in humans and non-human primates has not, though, been definitively established. Such a feedback pathway could have important functional, clinical, and experimental significance to the field of vision science and ophthalmology. METHODS: Following a comprehensive literature review (PubMed and Google Scholar, until July 2016), we present evidence regarding a system that can influence the bioelectrical activity of the retina in primates. RESULTS: Anatomical and physiological evidences are presented separately. Improvements in histological staining and the advent of retrograde nerve fiber tracers have allowed for more confidence in the identification of efferent optic nerve fibers, including back to their point of origin. CONCLUSION: Even with the accumulation of more modern anatomical and physiological evidence, some limitations and uncertainties about crucial details regarding the origins and role of a top-down, efferent system still exist. However, the summary of the evidence from earlier and more modern studies makes a compelling case in support of such a system in humans and non-human primates.
Assuntos
Olho/inervação , Neurônios Eferentes/fisiologia , Nervo Óptico/fisiologia , Primatas/fisiologia , Retina/fisiologia , Animais , Axônios/fisiologia , Humanos , Fibras Nervosas/fisiologia , Nervo Óptico/anatomia & histologia , Visão Ocular/fisiologiaRESUMO
The existence and functional relevance of efferent optic nerve fibers in mammals have long been debated. While anatomical evidence for cortico-retinal and retino-retinal projections is substantial, physiological evidence is lacking, as efferent fibers are few in number and are severed in studies of excised retinal tissue. Here we show that interocular connections contribute to retinal bioelectrical activity in adult mammals. Full-field flash electroretinograms (ERGs) were recorded from one or both eyes of Brown-Norway rats under dark-adapted (n = 16) and light-adapted (n = 11) conditions. Flashes were confined to each eye by an opaque tube that blocked stray light. Monocular flashes evoked a small (5-15 µV) signal in the nonilluminated eye, which was named "crossed ERG" (xERG). The xERG began under dark-adapted conditions with a positive (xP1) wave that peaked at 70-90 ms and ended with slower negative (xN1) and positive (xP2) waves from 200 to 400 ms. xN1 was absent under light-adapted conditions. Injection of tetrodotoxin in either eye (n = 15) eliminated the xERG. Intraocular pressure elevation of the illuminated eye (n = 6) had the same effect. The treatments also altered the ERG b-wave in both eyes, and the alterations correlated with xERG disappearance. Optic nerve stimulation (n = 3) elicited a biphasic compound action potential in the nonstimulated nerve with 10- to 13-ms latency, implying that the xERG comes from slow-conducting (W type) fibers. Monocular dye application (n = 7) confirmed the presence of retino-retinal ganglion cells in adult rats. We conclude that mammalian eyes communicate directly with each other via a handful of optic nerve fibers. The cross talk alters retinal activity in rats, and perhaps other animals.
Assuntos
Potenciais de Ação/fisiologia , Lateralidade Funcional/fisiologia , Neurônios/fisiologia , Retina/fisiologia , Vias Visuais/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Biofísica , Adaptação à Escuridão , Estimulação Elétrica , Eletrorretinografia , Olho/citologia , Lateralidade Funcional/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/fisiologia , Masculino , Neurônios/citologia , Neurônios/efeitos dos fármacos , Nervo Óptico/fisiologia , Estimulação Luminosa , Ratos , Retina/citologia , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/farmacologia , Vias Visuais/efeitos dos fármacosRESUMO
Luminance and contrast adaptation are neuronal mechanisms employed by the visual system to adjust our sensitivity to light. They are mediated by an assortment of cellular and network processes distributed across the retina and visual cortex. Both have been demonstrated in the eyes of many vertebrates, but only luminance adaptation has been shown in invertebrate eyes to date. Since the computational benefits of contrast adaptation should apply to all visual systems, we investigated whether this mechanism operates in horseshoe crab eyes, one of the best-understood neural networks in the animal kingdom. The spike trains of optic nerve fibers were recorded in response to light stimuli modulated randomly in time and delivered to single ommatidia or the whole eye. We found that the retina adapts to both the mean luminance and contrast of a white-noise stimulus, that luminance- and contrast-adaptive processes are largely independent, and that they originate within an ommatidium. Network interactions are not involved. A published computer model that simulates existing knowledge of the horseshoe crab eye did not show contrast adaptation, suggesting that a heretofore unknown mechanism may underlie the phenomenon. This mechanism does not appear to reside in photoreceptors because white-noise analysis of electroretinogram recordings did not show contrast adaptation. The likely site of origin is therefore the spike discharge mechanism of optic nerve fibers. The finding of contrast adaption in a retinal network as simple as the horseshoe crab eye underscores the broader importance of this image processing strategy to vision.
Assuntos
Adaptação Fisiológica , Sensibilidades de Contraste , Nervo Óptico/fisiologia , Retina/fisiologia , Potenciais de Ação , Animais , Caranguejos FerraduraRESUMO
Purpose: The purpose of this study was to determine the effects of ambient lighting on intraocular pressure (IOP) rhythmicity and variability. Methods: IOP was continuously recorded by wireless telemetry from rats under light/dark (LD), dark/light (DL), asymmetric (6L18D and 18D6L), constant dark (DD), and constant light (LL) cycles. In some DD experiments, 1-hour light pulses were presented at varying times. IOP rhythmicity and variability were respectively quantified via cosinor analysis and peak detection algorithms that identified transient and sustained fluctuations. Results: Rat IOP peaked at night and troughed during the day with LD amplitude of 8.7 ± 3.4 mm Hg. Rhythmicity persisted in DD and LL with a free-running period of 24.1 ± 0.3 and 25.2 ± 0.4 hours, respectively. Peak-to-trough amplitude was approximately 60% smaller in LL, often disappeared after 1 to 2 weeks as daytime IOP drifted 2.6 ± 1.5 mm Hg higher, and returned to approximately 60% larger in LD. Rhythmicity was similarly impacted but resynchronized to DL over 4 to 6 days. Rhythmicity was unaltered by short photoperiods (6L18D), but the nocturnal IOP elevation was markedly shortened by long photoperiods (18L6D) and temporarily lowered to daytime levels by light pulses during the subjective night. Transient and sustained event rate, amplitude, interval, and energy content were nearly identical in LD, DD, and LL. Conclusions: Aqueous humor dynamics of rat eyes are intrinsically configured to set IOP at daytime levels. Circadian clock input modulates these dynamics to elevate IOP at night. Light at night blocks this input, sending IOP back to daytime levels. Effects of abnormal lighting on IOP rhythmicity may contribute to pressure-related ocular neuropathies.
Assuntos
Ritmo Circadiano , Pressão Intraocular , Telemetria , Animais , Pressão Intraocular/fisiologia , Ratos , Ritmo Circadiano/fisiologia , Masculino , Iluminação , Ratos Sprague-Dawley , Tonometria Ocular , Fotoperíodo , LuzRESUMO
Intraocular pressure (IOP) is heavily influenced by the resistance of trabecular outflow pathways through which most of the aqueous humor produced by the eye continuously drains. The standard method of quantifying outflow resistance and other aspects of ocular fluid dynamics is eye cannulation, which allows for direct measurement and manipulation of IOP and flow in animal models. Since the method is invasive, indirect techniques that are slower and less accurate must be used for chronological studies. A novel technology is introduced that can autonomously measure outflow facility in conscious rats multiple times a day. A smart portable micropump infuses fluid into the eye through a permanently-implanted cannula and dynamically adjusts flow rate using a unique proportional feedback algorithm that sets IOP to a target level, even though IOP fluctuates erratically in awake free-moving animals. Pressure-flow data collected by the system from anesthetized rats were validated against intraocular recordings with commercial pressure and flow sensors. System and sensor estimates of outflow facility were indistinguishable, averaging 23 ± 3 nl·min-1·mmHg-1 across animals (n = 11). Pressure-flow data were then collected round-the-clock for several days from conscious rats, while outflow facility was measured every few hours. A significant diurnal facility rhythm was observed in every animal (n = 4), with mean daytime level of 22 ± 10 nl·min-1·mmHg-1 and mean nighttime level of 15 ± 7 nl·min-1·mmHg-1. The rhythm correlated with diurnal changes in IOP and likely contributed prominently to those changes based on the day-night swing in facility magnitude. Hence, the portable smart pump offers a unique tool for repeated long-term monitoring of outflow facility and other possible parameters of ocular health. It could also be useful in animal glaucoma studies for reversibly inducing acute or chronic ocular hypertension without explicitly damaging trabecular outflow pathways.
Assuntos
Glaucoma , Hipertensão Ocular , Ratos , Animais , Retroalimentação , Pressão Intraocular , Tonometria Ocular , Humor Aquoso/metabolismoRESUMO
Aqueous humor dynamics are commonly assessed by infusing fluid into the eye and measuring intraocular pressure (IOP). From the pressure-flow relationship, conventional outflow facility is estimated to study glaucomatous processes that lower facility or identify therapeutics that enhance facility in hopes of restoring healthy IOP levels. The relative merits and limitations of constant flow (CF), gravity-driven constant pressure (CPg), and pump-driven constant pressure (CPp) infusion techniques were explored via simulations of a lumped parameter viscoelastic model of the eye. Model parameter values were based on published perfusion system properties and outflow facility data from rodents. Step increases in pressure or flow were simulated without and with IOP noise recorded from enucleated eyes, anesthetized animals, and conscious animals. Steady-state response levels were determined using published window and ratio criteria. Model simulations show that all perfusion techniques estimate facility accurately and that ocular fluid dynamics set a hard limit on how fast measurements can be taken. This limit can be approached with CPg and CPp systems by increasing their gain but not with CF systems, which invariably take longest to settle. Facility experiment duration is further lengthened by inclusion of IOP noise, and data filtering is needed for steady-state detection with in vivo noise. The ratio criterion was particularly affected because noise in the flow data is amplified by the higher gain of CPg and CPp systems. A recursive regression method is introduced, which can ignore large transient IOP fluctuations that interfere with steady-state detection by fitting incoming data to the viscoelastic eye model. The fitting method greatly speeds up data collection without loss of accuracy, which could enable outflow facility measurements in conscious animals. The model may be generalized to study response dynamics to fluid infusion in other viscoelastic compartments of the body and model insights extended to optimize experiment design.
Assuntos
Glaucoma , Pressão Intraocular , Animais , Glaucoma/diagnóstico , Tonometria Ocular , Humor Aquoso/fisiologia , Perfusão/métodosRESUMO
There are no known drugs or drug combinations that promote substantial central nervous system axonal regeneration after injury. We used systems pharmacology approaches to model pathways underlying axonal growth and identify a four-drug combination that regulates multiple subcellular processes in the cell body and axons using the optic nerve crush model in rats. We intravitreally injected agonists HU-210 (cannabinoid receptor-1) and IL-6 (interleukin 6 receptor) to stimulate retinal ganglion cells for axonal growth. We applied, in gel foam at the site of nerve injury, Taxol to stabilize growing microtubules, and activated protein C to clear the debris field since computational models predicted that this drug combination regulating two subcellular processes at the growth cone produces synergistic growth. Physiologically, drug treatment restored or preserved pattern electroretinograms and some of the animals had detectable visual evoked potentials in the brain and behavioral optokinetic responses. Morphology experiments show that the four-drug combination protects axons or promotes axonal regrowth to the optic chiasm and beyond. We conclude that spatially targeted drug treatment is therapeutically relevant and can restore limited functional recovery.
RESUMO
The rat is a popular animal model for vision research, yet there is little quantitative information about the physiological properties of the cells that provide its brain with visual input, the retinal ganglion cells. It is not clear whether rats even possess the full complement of ganglion cell types found in other mammals. Since such information is important for evaluating rodent models of visual disease and elucidating the function of homologous and heterologous cells in different animals, we recorded from rat ganglion cells in vivo and systematically measured their spatial receptive field (RF) properties using spot, annulus, and grating patterns. Most of the recorded cells bore likeness to cat X and Y cells, exhibiting brisk responses, center-surround RFs, and linear or nonlinear spatial summation. The others resembled various types of mammalian W cell, including local-edge-detector cells, suppressed-by-contrast cells, and an unusual type with an ON-OFF surround. They generally exhibited sluggish responses, larger RFs, and lower responsiveness. The peak responsivity of brisk-nonlinear (Y-type) cells was around twice that of brisk-linear (X-type) cells and several fold that of sluggish cells. The RF size of brisk-linear and brisk-nonlinear cells was indistinguishable, with average center and surround diameters of 5.6 ± 1.3 and 26.4 ± 11.3 deg, respectively. In contrast, the center diameter of recorded sluggish cells averaged 12.8 ± 7.9 deg. The homogeneous RF size of rat brisk cells is unlike that of cat X and Y cells, and its implication regarding the putative roles of these two ganglion cell types in visual signaling is discussed.
Assuntos
Potenciais de Ação/fisiologia , Retina/citologia , Células Ganglionares da Retina/fisiologia , Campos Visuais/fisiologia , Animais , Masculino , Distribuição Normal , Estimulação Luminosa/métodos , Ratos , Ratos Long-Evans , Limiar Sensorial/fisiologia , Vias Visuais/fisiologiaRESUMO
Ocular diseases can deteriorate vision to the point of blindness and thus can have a major impact on the daily life of an individual. Conventional therapies are unable to provide absolute therapy for all ocular diseases due to the several limitations during drug delivery across the blood-retinal barrier, making it a major clinical challenge. With recent developments, the vast number of publications undergird the need for nanotechnology-based drug delivery systems in treating ocular diseases. The tool of nanotechnology provides several essential advantages, including sustained drug release and specific tissue targeting. Additionally, comprehensive in vitro and in vivo studies have suggested a better uptake of nanoparticles across ocular barriers. Nanoparticles can overcome the blood-retinal barrier and consequently increase ocular penetration and improve the bioavailability of the drug. In this review, we aim to summarize the development of organic and inorganic nanoparticles for ophthalmic applications. We highlight the potential nanoformulations in clinical trials as well as the products that have become a commercial reality.
RESUMO
The output of retinal ganglion cells depends on local and global aspects of the visual scene. The local receptive field is well studied and classically consists of a linear excitatory center and a linear antagonistic surround. The global receptive field contains pools of nonlinear subunits that are distributed widely across the retina. The subunit pools mediate in uncertain ways various nonlinear behaviors of ganglion cells, like temporal-frequency doubling, saccadic suppression, and contrast adaptation. To clarify mechanisms of subunit function, we systematically examined the effect of remote grating patterns on the spike activity of cat X- and Y-type ganglion cells in vivo. We present evidence for two distinct subunit types based on spatiotemporal relationships between response nonlinearities elicited by remote drifting and contrast-reversing gratings. One subunit type is excitatory and activated by gratings of approximately 0.1 cycles per degree, while the other is inhibitory and activated by gratings of approximately 1 cycle per degree. The two subunit pools contribute to a global gain control mechanism that differentially modulates ganglion cell response dynamics, particularly for ON-center cells, where excitatory and inhibitory subunit stimulation respectively makes responses to antipreferred and preferred contrast steps more transient. We show that the excitatory subunits also have a profound influence on spatial tuning, turning cells from lowpass into bandpass filters. Based on difference-of-Gaussians model fits to tuning curves, we attribute the increased bandpass selectivity to changes in center-surround strength and relative phase and not center-surround size. A conceptual model of the extraclassical receptive field that could explain many observed phenomena is discussed.
Assuntos
Potenciais de Ação/fisiologia , Sensibilidades de Contraste/fisiologia , Retina/citologia , Células Ganglionares da Retina/fisiologia , Percepção Espacial/fisiologia , Animais , Gatos , Modelos Neurológicos , Dinâmica não Linear , Orientação/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa/métodos , Psicofísica , Células Ganglionares da Retina/classificação , Campos Visuais/fisiologia , Vias Visuais/fisiologiaRESUMO
To accommodate the wide input range over which the visual system operates within the narrow output range of spiking neurons, the retina adjusts its sensitivity to the mean light level so that retinal ganglion cells can faithfully signal contrast, or relative deviations from the mean luminance. Given the large operating range of the visual system, the majority of work on luminance adaptation has involved logarithmic changes in light level. We report that luminance gain controls are recruited for remarkably small fluctuations in luminance as well. Using spike recordings from the rat optic tract, we show that ganglion cell responses to a brief flash of light are modulated in amplitude by local background fluctuations as little as 15% contrast. The time scale of the gain control is rapid (<125 ms), at least for on cells. The retinal locus of adaptation precedes the ganglion cell spike generator because response gain changes of on cells were uncorrelated with firing rate. The mechanism seems to reside within the inner retinal network and not in the photoreceptors, because the adaptation profiles of on and off cells differed markedly. The response gain changes follow Weber's law, suggesting that network mechanisms of luminance adaptation described in previous work modulates retinal ganglion cell sensitivity, not just when we move between different lighting environments, but also as our eyes scan a visual scene. Finally, we show that response amplitude is uniformly reduced for flashes on a modulated background that has spatial contrast, indicating that another gain control that integrates luminance signals nonlinearly over space operates within the receptive field center of rat ganglion cells.
Assuntos
Adaptação Fisiológica/fisiologia , Sensibilidades de Contraste/fisiologia , Células Ganglionares da Retina/fisiologia , Potenciais de Ação/fisiologia , Animais , Modelos Neurológicos , Dinâmica não Linear , Estimulação Luminosa/métodos , Ratos , Retina/citologiaRESUMO
Glaucoma-like neuropathies can be experimentally induced by disturbing aqueous outflow from the eye, resulting in intraocular pressure (IOP) changes that are variable in magnitude and time course and permanent in duration. This study introduces a novel method of glaucoma induction that offers researchers round-the-clock measurement and reversible control of IOP for the first time. One eye of Brown-Norway rats was implanted with a cannula tethered to a pressure sensor and aqueous reservoir. IOP was raised 10 mmHg for weeks-to-months in treated animals and unaltered in control animals. Counts of Brn3a-expressing retinal ganglion cells (RGCs) in implanted eyes were indistinguishable from non-implanted eyes in control animals and 15 ± 2%, 23 ± 4%, and 38 ± 4% lower in animals exposed to 2, 4, and 9 weeks of IOP elevation. RGC loss was greater in peripheral retina at 2 weeks and widespread at longer durations. Optic nerves also showed progressive degeneration with exposure duration, yet conventional outflow facility of implanted eyes was normal (24.1 ± 2.9 nl/min/mmHg) even after 9-weeks elevation. Hence, this infusion-based glaucoma model exhibits graded neural damage with unimpaired outflow pathways. The model further revealed a potentially-significant finding that outflow properties of rat eyes do not remodel in response to chronic ocular hypertension.
Assuntos
Glaucoma/fisiopatologia , Pressão Intraocular , Animais , Modelos Animais de Doenças , Glaucoma/patologia , Masculino , Nervo Óptico/patologia , Ratos , Células Ganglionares da Retina/patologiaRESUMO
Rats are a popular animal model for vision research and for investigating disorders of the visual system. The study aimed to quantify the spatiotemporal contrast sensitivity function (CSF) of healthy adult Brown-Norway rats under scotopic and photopic illumination. Animals were trained to jump onto the one of two adjacent platforms behind which was displayed a sinewave grating pattern. Contrast thresholds of light- and dark-adapted rats were determined using a staircase method of adjustment for gratings that varied in spatial frequency (sf) and temporal frequency (tf) and ranged several log-units in mean luminance. Photopic CSFs showed strong bandpass spatial tuning, consistent with prior measurements, and weak bandpass temporal tuning. CSFs were parameterized by a truncated log-parabola model, yielding a peak contrast sensitivity of 52⯱â¯9, peak sf of 0.17⯱â¯0.05 cycles/degree, sf limit of 1.6⯱â¯0.3 cycles/degree, low sf attenuation of 85⯱â¯9%, peak tf of 1.7⯱â¯1.1â¯Hz, extrapolated tf limit of 166⯱â¯44â¯Hz, and low tf attenuation of 55⯱â¯12%. CSFs became more lowpass and decreased systematically in contrast sensitivity and spatiotemporal acuity as mean luminance was reduced. CSFs were also measured via the visual head-tracking reflex. Photopic contrast sensitivity, spatial acuity, and temporal acuity were all markedly below that of the grating detection task and optomotor findings for other rat strains. The CSF data provide a comprehensive and quantitative description of rat spatial and temporal vision and a benchmark for evaluating effects of ocular diseases on their ability to see.
Assuntos
Visão de Cores , Sensibilidades de Contraste , Animais , Iluminação , RatosRESUMO
Spike conduction velocity characteristically differs between myelinated and unmyelinated axons. Here we test whether spikes of myelinated and unmyelinated paths differ in other respects by measuring rat retinal ganglion cell (RGC) spike duration in the intraretinal, unmyelinated nerve fiber layer and the extraretinal, myelinated optic nerve and optic chiasm. We find that rapid spike firing and illumination broaden spikes in intraretinal axons but not in extraretinal axons. RGC axons thus initiate spikes intraretinally and normalize spike duration extraretinally. Additionally, we analyze spikes that were recorded in a previous study of rhesus macaque retinogeniculate transmission and find that rapid spike firing does not broaden spikes in optic tract. The spike normalization we find reduces the number of spike properties that can change during RGC light responses. However, this is not because identical spikes fire in all axons. Instead, our recordings show that different subtypes of RGC generate axonal spikes of different durations and that the differences resemble spike duration increases that alter neurotransmitter release from other neurons. Moreover, previous studies have shown that RGC spikes of shorter duration can fire at higher maximum frequencies. These properties should facilitate signal transfer by different mechanisms at RGC synapses onto subcortical target neurons.
Assuntos
Axônios , Células Ganglionares da Retina , Animais , Macaca mulatta , Quiasma Óptico , Nervo Óptico , Ratos , RetinaRESUMO
Action potentials were recorded from rat retinal ganglion cell fibers in the presence of a uniform field, and the maintained discharge pattern was characterized. Spike trains recorded under ketaminexylazine. The majority of cells had multimodal interval distributions, with the first peak in the range of 25.00.97). Both ON and OFF cells show serial correlations between adjacent interspike intervals, while ON cells also showed second-order correlations. Cells with multimodal interval distribution showed a strong peak at high frequencies in the power spectra in the range of 28.9-41.4 Hz. Oscillations were present under both anesthetic conditions and persisted in the dark at a slightly lower frequency, implying that the oscillations are generated independent of any light stimulus but can be modulated by light level. The oscillation frequency varied slightly between cells of the same type and in the same eye, suggesting that multiple oscillatory generating mechanisms exist within the retina. Cells with high-frequency oscillations were described well by an integrate-and-fire model with the input consisting of Gaussian noise plus a sinusoid where the phase was jittered randomly to account for the bandwidth present in the oscillations.
Assuntos
Ratos , Células Ganglionares da Retina/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/efeitos da radiação , Analgésicos/farmacologia , Anestésicos Dissociativos/farmacologia , Animais , Ketamina/farmacologia , Luz , Modelos Neurológicos , Oscilometria , Ratos Endogâmicos BN , Tempo de Reação , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/efeitos da radiação , Xilazina/farmacologiaRESUMO
Purpose: The study aimed to provide a quantitative description of aqueous humor dynamics in healthy rat eyes. Methods: One eye of 26 anesthetized adult Brown-Norway rats was cannulated with a needle connected to a perfusion pump and pressure transducer. Pressure-flow data were measured in live and dead eyes by varying pump rate (constant-flow technique) or by modulating pump duty cycle to hold intraocular pressure (IOP) at set levels (modified constant-pressure technique). Data were fit by the Goldmann equation to estimate conventional outflow facility (C) and unconventional outflow rate (Fun). Parameter estimates were respectively checked by inserting a shunt of similar conductance into the eye and by varying eye hydration methodology. Results: Rat IOP averaged 14.6 ± 1.9 mm Hg at rest. Pressure-flow data were repeatable and indistinguishable for the two perfusion techniques, yielding C = 0.023 ± 0.002 µL/min/mm Hg and Fun = 0.096 ± 0.024 µL/min. C was similar for live and dead eyes and increased upon shunt insertion by an amount equal to shunt conductance, validating measurement accuracy. At 100% humidity Fun dropped to 0.003 ± 0.030 µL/min. Physiological washout was not observed (-0.35 ± 0.65%/h), and trabecular anatomy looked normal. Conclusions: Rat aqueous humor dynamics are intermediate in magnitude compared to those in mice and humans, consistent with species differences in eye size. C does not change with time or death. Evaporation complicates measurement of Fun even when eyes are not enucleated. Absence of washout is a notable finding seen only in mouse and human eyes to date.