RESUMO
The first retinal synapse, photoreceptorâbipolar cell (BC), is both anatomically and functionally complex. Within the same synaptic region, a change in presynaptic glutamate release is sensed by both ON BCs (DBCs) via the metabotropic glutamate receptor 6 (mGluR6), and OFF BCs (HBCs) via ionotropic glutamate receptors to establish parallel signaling pathways that preferentially encode light increments (ON) or decrements (OFF), respectively. The synaptic structural organization of ON and OFF-type BCs at the photoreceptor terminal differs. DBCs make an invaginating synapse that contains a diverse but incompletely understood complex of interacting proteins (signalplex). HBCs make primarily flat contacts that contain an apparent different set of proteins that is equally uncharacterized. LRIT3 is a synaptic protein known to be essential for ON pathway visual function. In both male and female mice, we demonstrate that LRIT3 interacts with and is required for expression of nyctalopin, and thus TRPM1 at all DBC dendritic tips, but DBC signalplex components are not required for LRIT3 expression. Using whole-cell and multielectrode array (MEA) electrophysiology and glutamate imaging, we demonstrate that the loss of LRIT3 impacts both ON and OFF signaling pathway function. Without LRIT3, excitatory input to type 1 BCs is reduced, as are the visually evoked responses of many OFF retinal ganglion cells (RGCs). We conclude that the absence of LRIT3 expression disrupts excitatory input to OFF BCs and, thus disrupts the normal function of OFF RGCs.
Assuntos
Proteínas de Membrana , Retina , Células Bipolares da Retina , Transdução de Sinais , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , SinapsesRESUMO
Congenital nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here, we investigated whether nystagmus associated with congenital stationary night blindness (CSNB) results from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lacked functional nyctalopin protein (NYX, nyx) in ON bipolar cells (BCs) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4-7 Hz. nob ON direction-selective ganglion cells (DSGCs), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GCs) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light when contrast was present. Retinal pharmacological and genetic manipulations that blocked nob GC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced the oscillation frequency of nob GCs also reduced the oscillation frequency of their eye movements. We conclude that, in nob mice, synchronized oscillations of retinal GCs, most likely the ON-DCGCs, cause nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of congenital nystagmus, paving the way for development of therapeutic strategies.
Assuntos
Oftalmopatias Hereditárias/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Miopia/fisiopatologia , Cegueira Noturna/fisiopatologia , Nistagmo Congênito/etiologia , Células Ganglionares da Retina/fisiologia , Animais , Pré-Escolar , Modelos Animais de Doenças , Feminino , Humanos , Lactente , Masculino , Camundongos KnockoutRESUMO
Throughout the CNS, interactions between pre- and postsynaptic adhesion molecules establish normal synaptic structure and function. Leucine-rich repeat (LRR) domain-containing proteins are a large family that has a diversity of ligands, and their absence can cause disease. At the first retinal synapse, the absence of LRIT3 expression leads to the disassembly of the postsynaptic glutamate signaling complex (signalplex) expressed on depolarizing bipolar cell (DBC) dendrites. The prevalent view is that assembly of the signalplex results from direct postsynaptic protein:protein interactions. In contrast, we demonstrate that LRIT3 is expressed presynaptically, in rod photoreceptors (rods), and when we restore LRIT3 expression in Lrit3-/- rods, we restore expression of the postsynaptic glutamate signalplex and rod-driven vision. Our results demonstrate that, in the retina, the LRR-containing protein LRIT3 acts as a transsynaptic organizer of the postsynaptic complex required for normal synaptic function.
Assuntos
Ácido Glutâmico/metabolismo , Proteínas de Membrana/metabolismo , Sinapses/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Dendritos/metabolismo , Dendritos/fisiologia , Feminino , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Células Bipolares da Retina/metabolismo , Células Bipolares da Retina/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Sinapses/fisiologia , Potenciais SinápticosRESUMO
GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal depolarizing bipolar cells (DBCs). Mutations in GRM6 lead to DBC dysfunction and underlie the human condition autosomal recessive complete congenital stationary night blindness. Mouse mutants for Grm6 are important models for this condition. Here we report a new Grm6 mutant, identified in an electroretinogram (ERG) screen of mice maintained at The Jackson Laboratory. The Grm6nob8 mouse has a reduced-amplitude b-wave component of the ERG, which reflects light-evoked DBC activity. Sequencing identified a missense mutation that converts a highly conserved methionine within the ligand binding domain to leucine (p.Met66Leu). Consistent with prior studies of Grm6 mutant mice, the laminar size and structure in the Grm6nob8 retina were comparable to control. The Grm6nob8 phenotype is distinguished from other Grm6 mutants that carry a null allele by a reduced but not absent ERG b-wave, decreased but present expression of mGluR6 at DBC dendritic tips, and mislocalization of mGluR6 to DBC somas. Consistent with a reduced but not absent b-wave, there were a subset of retinal ganglion cells whose responses to light onset have times to peak within the range of those in control retinas. These data indicate that the p.Met66Leu mutant mGluR6 is trafficked less than control. However, the mGluR6 that is localized to the DBC dendritic tips is able to initiate DBC signal transduction. The Grm6nob8 mouse extends the Grm6 allelic series and will be useful for elucidating the role of mGluR6 in DBC signal transduction and in human disease.NEW & NOTEWORTHY This article describes a mouse model of the human disease complete congenital stationary night blindness in which the mutation reduces but does not eliminate GRM6 expression and bipolar cell function, a distinct phenotype from that seen in other Grm6 mouse models.
Assuntos
Oftalmopatias Hereditárias/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Mutação de Sentido Incorreto , Miopia/metabolismo , Cegueira Noturna/metabolismo , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Células Bipolares da Retina/metabolismo , Visão Ocular/fisiologia , Animais , Dendritos/metabolismo , Dendritos/patologia , Dendritos/efeitos da radiação , Modelos Animais de Doenças , Eletrorretinografia , Proteínas de Escherichia coli , Oftalmopatias Hereditárias/genética , Oftalmopatias Hereditárias/patologia , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Transgênicos , Miopia/genética , Miopia/patologia , Cegueira Noturna/genética , Cegueira Noturna/patologia , Células Bipolares da Retina/patologia , Fatores de TranscriçãoRESUMO
The morphological consequences of retinal photoreceptor degeneration are well documented. Much less is known about changes in visual function during degeneration and whether central visual structures directly reflect changes in retinal ganglion cell (RGC) function. To address this, we compared changes in visual function of RGCs and cells in the superior colliculus (SC) in transgenic (Tg) P23H-1 rats, a model of retinitis pigmentosa (RP), and wild-type (WT) rats at postnatal days 35-50 (P35-50) and P300. RGCs were classified on the basis of their responses to light: onset (ON), offset (OFF), or both (ON-OFF). The distribution of ON, OFF, and ON-OFF RGCs is similar between WT and P35 Tg P23H-1 rats. By P300, many Tg P23H-1 RGCs are nonresponsive (NR). At this age, there is a sharp decline in ON and ON-OFF RGCs, and the majority that remain are OFF RGCs. Spontaneous rhythmic activity was observed in many RGCs at P300, but only in OFF or NR RGCs. In the SC, WT and P50 Tg P23H-1 responses are similar. At P300, Tg P23H-1 ON SC responses declined but OFF responses increased. We examined postsynaptic glutamate receptor expression located on the bipolar cells (BC), where the ON and OFF pathways arise. At P150, metabotropic glutamate receptor 6 (mGluR6) expression is lower than in WT, consistent with a decrease in ON RGC responses. GluR4 expression, an ionotropic glutamate receptor associated with OFF BCs, appears similar to that in WT. The loss of ON responses in Tg P23H-1 RGCs and in the SC is conserved and related to reduced mGluR6 signaling.
Assuntos
Células Bipolares da Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Retinose Pigmentar/fisiopatologia , Colículos Superiores/fisiopatologia , Vias Visuais/fisiologia , Potenciais de Ação , Envelhecimento/fisiologia , Animais , Modelos Animais de Doenças , Imuno-Histoquímica , Ratos Transgênicos , Receptores de Glutamato Metabotrópico/metabolismo , Técnicas de Cultura de TecidosRESUMO
We studied the spatial arrangement of L- and M-cone driven electroretinograms (ERGs) reflecting the activity of magno- and parvocellular pathways. L- and M-cone isolating sine wave stimuli were created with a four primary LED stimulator using triple silent substitution paradigms. Temporal frequencies were 8 and 12 Hz, to reflect cone opponent activity, and 30, 36 and 48 Hz to reflect luminance activity. The responses were measured for full-field stimuli and for different circular and annular stimuli. The ERG data confirm the presence of two different mechanisms at intermediate and high temporal frequencies. The responses measured at high temporal frequencies strongly depended upon spatial stimulus configuration. In the full-field conditions, the L-cone driven responses were substantially larger than the full-field M-cone driven responses and also than the L-cone driven responses with smaller stimuli. The M-cone driven responses at full-field and with 70° diameter stimuli displayed similar amplitudes. The L- and M-cone driven responses measured at 8 and 12 Hz were of similar amplitude and approximately in counter-phase. The amplitudes were constant for most stimulus configurations. The results indicate that, when the ERG reflects luminance activity, it is positively correlated with stimulus size. Beyond 35° retinal eccentricity, the retina mainly contains L-cones. Small stimuli are sufficient to obtain maximal ERGs at low temporal frequencies where the ERGs are also sensitive to cone-opponent processing.
Assuntos
Células Fotorreceptoras Retinianas Cones/fisiologia , Adulto , Eletrorretinografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Células Fotorreceptoras Retinianas Cones/citologia , Análise EspacialRESUMO
Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission.
Assuntos
Células Amácrinas/citologia , Modelos Animais de Doenças , Células Ependimogliais/citologia , Células Bipolares da Retina/citologia , Retinose Pigmentar/cirurgia , Visão Ocular/fisiologia , Próteses Visuais , Células Amácrinas/fisiologia , Animais , Biomarcadores/metabolismo , Eletrorretinografia , Células Ependimogliais/fisiologia , Técnica Indireta de Fluorescência para Anticorpo , Proteína Glial Fibrilar Ácida/metabolismo , Implantação de Prótese , Proteína Quinase C-alfa/metabolismo , Ratos , Ratos Mutantes , Ratos Transgênicos , Células Bipolares da Retina/fisiologia , Retinose Pigmentar/metabolismo , Retinose Pigmentar/patologia , Acuidade Visual/fisiologiaRESUMO
OBJECTIVE: In clinical trials, retinitis pigmentosa patients implanted with a retinal prosthetic device show enhanced spatial vision, including the ability to read large text and navigate. New prosthetics aim to increase spatial resolution by decreasing pixel/electrode size and limiting current spread. To examine spatial resolution of a new prosthetic design, we characterized and compared two photovoltaic array (PVA) designs and their interaction with the retina after subretinal implantation in transgenic S334ter line 3 rats (Tg S334ter-3). APPROACH: PVAs were implanted subretinally at two stages of degeneration and assessed in vivo using extracellular recordings in the superior colliculus (SC). Several aspects of this interaction were evaluated by varying duration, irradiance and position of a near infrared laser focused on the PVA. These characteristics included: activation threshold, response linearity, SC signal topography and spatial localization. The major design difference between the two PVA designs is the inclusion of local current returns in the newer design. MAIN RESULTS: When tested in vivo, PVA-evoked response thresholds were independent of pixel/electrode size, but differ between the new and old PVA designs. Response thresholds were independent of implantation age and duration (⩽7.5 months). For both prosthesis designs, threshold intensities were within established safety limits. PVA-evoked responses require inner retina synaptic transmission and do not directly activate retinal ganglion cells. The new PVA design evokes local retinal activation, which is not found with the older PVA design that lacks local current returns. SIGNIFICANCE: Our study provides in vivo evidence that prosthetics make functional contacts with the inner nuclear layer at several stages of degeneration. The new PVA design enhances local activation within the retina and SC. Together these results predict that the new design can potentially harness the inherent processing within the retina and is likely to produce higher spatial resolution in patients.
Assuntos
Retina/fisiologia , Retinose Pigmentar/fisiopatologia , Retinose Pigmentar/terapia , Colículos Superiores , Próteses Visuais , Animais , Potenciais Evocados Visuais/fisiologia , Lasers , Estimulação Luminosa , Desenho de Prótese , Implantação de Prótese , Ratos , Ratos Long-Evans , Transmissão SinápticaRESUMO
L- and M-cone driven on- and off- ERG responses and their interactions were examined using full field stimuli with sawtooth temporal profiles. The effects of temporal frequency and contrast were studied. ERG recordings were obtained from 21 trichromatic, 1 protanopic, and 1 deuteranopic subjects. ERGs to L-cone increments and decrements resembled those to M-cone decrements and increments, respectively (i.e., of the opposite polarity). Temporal frequency and contrast had little effect on the implicit times. All response components varied linearly with contrast. When stimulated simultaneously, the responsivities of most components were larger for counterphase than for inphase modulation. The retinal processing leading to an ERG response is reversed for L- and M-cone driven responses.
Assuntos
Eletrorretinografia/métodos , Estimulação Luminosa , Células Fotorreceptoras Retinianas Cones/citologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
In this study, the on- and off-responses elicited by luminance square wave and sawtooth stimuli at different temporal frequencies and contrasts are described quantitatively. Adding on- and off-responses reveals response asymmetries. Full-field stimuli were produced using a Ganzfeld bowl with arrays of light-emitting diodes (LEDs) as light sources. ERG responses were recorded from six normal subjects. The amplitudes and implicit times of components of the on- and off-responses and the additions were analyzed. The amplitudes of the on-, off- and addition components elicited by square wave stimuli did not depend on temporal frequency with the exception of the late negative components, which decreased with increasing temporal frequency up to 4 Hz. The amplitudes of all components elicited by sawtooth stimuli, except the P-on, decreased with increasing temporal frequency. The amplitude of all components elicited by square wave and sawtooth stimuli were positively correlated with stimulus contrast. The implicit times of the on-components to square wave stimuli and all response components to sawtooth stimuli decreased with increasing temporal frequency. Contrast had an effect on the implicit times of the N-on, P-on, P-off and P-add components elicited by square wave stimuli and the N-on, P-on, P-add and LN-on components elicited by sawtooth stimuli. The asymmetries between on- and off-responses can possibly be used to reveal inner retinal contributions and may therefore be interesting in detecting glaucomatous changes...
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Eletrorretinografia , Estimulação LuminosaRESUMO
In this study, the on- and off-responses elicited by luminance square wave and sawtooth stimuli at different temporal frequencies and contrasts are described quantitatively. Adding on- and off-responses reveals response asymmetries. Full-field stimuli were produced using a Ganzfeld bowl with arrays of light-emitting diodes (LEDs) as light sources. ERG responses were recorded from six normal subjects. The amplitudes and implicit times of components of the on- and off-responses and the additions were analyzed. The amplitudes of the on-, off- and addition components elicited by square wave stimuli did not depend on temporal frequency with the exception of the late negative components, which decreased with increasing temporal frequency up to 4 Hz. The amplitudes of all components elicited by sawtooth stimuli, except the P-on, decreased with increasing temporal frequency. The amplitude of all components elicited by square wave and sawtooth stimuli were positively correlated with stimulus contrast. The implicit times of the on-components to square wave stimuli and all response components to sawtooth stimuli decreased with increasing temporal frequency. Contrast had an effect on the implicit times of the N-on, P-on, P-off and P-add components elicited by square wave stimuli and the N-on, P-on, P-add and LN-on components elicited by sawtooth stimuli. The asymmetries between on- and off-responses can possibly be used to reveal inner retinal contributions and may therefore be interesting in detecting glaucomatous changes.(AU)
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Eletrorretinografia , Estimulação LuminosaRESUMO
The aim of this study is to measure the on- and off-responses and their response asymmetries elicited by sawtooth stimuli in normal subjects and glaucoma patients. Furthermore, the correlation between the ERGs and other functional and structural parameters are investigated. Full-field stimuli were produced using a Ganzfeld bowl with Light Emitting Diodes (LEDs) as light sources. On- and off-response ERGs were recorded from 17 healthy subjects, 12 pre-perimetric and 15 perimetric glaucoma patients using 4-Hz luminance rapid-on and rapid-off sawtooth stimuli (white light; mean luminance 55 cd/m(2)) at 100% contrast. The on- and off-responses were added to study response asymmetries. In addition, flash ERGs were elicited by red stimuli (200 cd/m(2)) on a blue background (10 cd/m(2)). The mean deviations (MD) of the visual field defects were obtained by standard automated perimetry. The retinal nerve fibre layer thickness (RNFLT) was measured with Spectral Domain Optical Coherence Tomography (SOCT). We studied the correlation between ERG response amplitudes, visual field mean deviation (MDs) and RNFLT values. The on-responses showed an initial negative (N-on) followed by a positive (P-on), a late positive (LP-on) and a late negative responses (LN-on). The off-responses showed an initial positive (P-off) a late positive (LP-off) and a late negative response (LN-off). The addition of on- and off-responses revealed an initial positive (P-add) and a late negative response (LN-add). The on-response components (N-on, P-on and LN-on) in the glaucoma patients were relatively similar to those of the control subjects. However, the LP-on was significantly elevated (p = 0.03) in perimetric patients. The LP-off was significantly elevated (p < 0.001), and the amplitude of LN-off was significantly reduced in perimetric patients (p = 0.02). The LN-add amplitude was significantly reduced (p < 0.001) and delayed (p = 0.03) in perimetric patients. The amplitudes of the LN-off and LN-add ERG components were significantly correlated with the PhNR in the flash ERG (LN-off: p = 0.01; LN-add: p < 0.001) and with RNFLT (LN-off: p = 0.006; LN-add: p = 0.001). On- and off-response ERGs and their response asymmetries, elicited by sawtooth stimuli, are altered in the glaucoma patients. The late components are affected. Changes in the late negative components are correlated with structural and other functional changes.
Assuntos
Eletrorretinografia , Glaucoma de Ângulo Aberto/fisiopatologia , Doenças do Nervo Óptico/fisiopatologia , Retina/fisiologia , Idoso , Feminino , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Estimulação Luminosa , Tomografia de Coerência Óptica , Testes de Campo Visual , Campos VisuaisRESUMO
Electroretinographic responses to cone and rod isolating stimuli and to simultaneous L- and M-cone modulation were measured at different temporal frequencies between 2 and 60 Hz and at two mean luminances using a four primary stimulator. The responses driven by each photoreceptor type had distinct characteristics. The responses to stimuli containing L- and/or M-cone stimulation indicated the presence of two underlying mechanisms that were active in distinct frequency regions. Between 2 and 12 Hz, the responses displayed properties that were reminiscent of the L-M-cone opponent system. At higher temporal frequencies, the electroretinograms were more determined by the luminance content in the stimuli.
Assuntos
Eletrorretinografia/métodos , Células Fotorreceptoras Retinianas Cones/citologia , Células Fotorreceptoras Retinianas Bastonetes/citologia , Adulto , Cor , Humanos , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Estimulação Luminosa , Fatores de Tempo , Adulto JovemRESUMO
Flash electroretinogram responses were measured in normal subjects to different chromatic combinations of flashes and backgrounds. The amplitudes of the flash response components were measured at different flash strengths and could be described by a generalized Naka-Rushton function. The measurements were repeated at different background luminances to study adaptation effects. It was found that when flash strength and background luminance were expressed in photometric terms (cd s/m² and cd/m², respectively), then the responses were very similar for all chromatic combinations with the exception of the condition in which blue (peak wavelength 458 nm) was flashed upon an orange (peak wavelength 591 nm) background. We propose that in this condition, a second (possibly S-cone or rod-driven) mechanism intrudes. The negative response after the b-wave (here called "photopic negative response" or PhNR for all conditions) is thought to reflect ganglion cell activity and was also largest at this condition. Responses were measured to the 458 nm flash on 591 nm background and the reversed combination in a population of 39 normal subjects and 49 glaucoma patients. It was found that the PhNR amplitude was affected by glaucoma in all conditions. Other component parameters, reflecting responses and adaptation dynamics, were not altered. The best stimulus condition among the conditions used to separate the PhNR amplitude of normals and patients was a 1 cd s/m² 458 nm flash on a 10 cd/m² 591 nm background.
Assuntos
Eletrorretinografia/métodos , Glaucoma/fisiopatologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Adulto , Visão de Cores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação LuminosaRESUMO
PURPOSE: To measure heterochromatic flicker electroretinograms (ERGs) at high (36 Hz) and intermediate (12 Hz) temporal frequencies to evaluate luminance and cone opponent responses, respectively, in glaucoma eyes with (perimetric) and without (preperimetric) visual field defects. METHODS: Flicker ERGs were recorded from one randomly chosen dilated eye of 32 patients (mean age, 61 ± 11 years; 15 men, 17 women) from the Erlangen Glaucoma Registry and from 24 healthy volunteers (mean age, 43 ± 11 years; 14 men, 10 women). Red and green light-emitting diodes in a Ganzfeld stimulator were sine wave-modulated in counterphase. The responses were measured at 36 Hz, the frequency at which ERGs reflect activity of the luminance pathway, and at 12 Hz, the frequency at which ERGs reflect chromatic activity. RESULTS: Response amplitudes were similar in glaucoma patients and controls. Phase differences were observed in patients with visual field defects (perimetric) compared with the control group at 36 and 12 Hz in the first harmonic and second harmonic responses. Patients without visual field defects (preperimetric) showed phase differences for the second harmonic component at 36 Hz. No age effect on response amplitudes and phases was found in any of the subject groups (controls and patients). CONCLUSIONS: The responses displayed phase differences but not amplitude differences in perimetric glaucoma patients at both 36 and 12 Hz, suggesting that both magnocellular and parvocellular pathways are affected. Preperimetric glaucoma patients also showed phase differences. The response phase may be sensitive to early dysfunction of the inner retina. (ClinicalTrials.gov number, NCT00494923).
Assuntos
Visão de Cores , Eletrorretinografia , Glaucoma de Ângulo Aberto/fisiopatologia , Iluminação , Células Fotorreceptoras Retinianas Cones/fisiologia , Campos Visuais , Adulto , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Testes de Campo VisualRESUMO
Recent studies suggest a diagnostic value of the photopic negative response (PhNR) with a long-duration stimulus. The aim of this study was to record the on and off responses of the photopic fullfield electroretinogram (ERG) in normal subjects and glaucoma patients. We focused on different waves of the responses after onset and offset of the long-duration stimulus ERG. Photopic fullfield ERGs were recorded in response to a white bright LED flash on a white 20 cd/m(2) background. Stimulus luminances were 40, 60 and 80 cd/m(2). Responses were averaged using a flash duration of 240 ms and an offset period of 500 ms. We examined 19 healthy subjects, 27 patients with glaucomatous optic disc atrophy and 7 ocular hypertensive patients. The amplitudes and implicit times of the on and off responses of the human ERG depended on flash luminance. Comparing patients with glaucoma and healthy subjects for the 60 cd/m² flash, there was a significant change in the PhNRs (at onset: P < 0.01, at offset: P < 0.001) of the d-wave and of the i-wave at offset (P < 0.01). No significant difference was found for peak times of the fullfield ERG and for a- and b-wave amplitudes. PhNR amplitudes were significantly correlated with mean thickness of retinal nerve fibre layer as measured with OCT. In comparison with the normal photopic long-flash ERG, glaucoma patients showed changes in the PhNR amplitude following stimulus onset and in waves following stimulus offset.
Assuntos
Visão de Cores , Eletrorretinografia/métodos , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Idoso , Atrofia , Estudos de Coortes , Feminino , Glaucoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/patologia , Hipertensão Ocular/fisiopatologia , Disco Óptico/patologia , Estimulação Luminosa/métodos , Retina/patologiaRESUMO
Full-field electroretinograms were recorded from five normal human subjects using white light (mean luminance: 250 cd/m2) sine wave stimuli at different frequencies and contrasts. In agreement with previous studies, we found that the amplitude of the fundamental component displayed a dip at about 12 Hz, coinciding with a maximum in the second harmonic component, indicating frequency doubling of the responses. By including measurements at different contrasts, we were able to recognize two (sine-like and transient) response components. We found that the waveform of the transient response was relatively frequency independent. An algorithm to separate the two components was developed. The interaction between these two components can explain the frequency-doubled responses around 12 Hz. The sine-like component is more linear and prominent in the low-frequency region, whereas the transient seems to be more nonlinear and prominent in the high-frequency region.