scholarly journals Early localized alterations of the retinal inner plexiform layer in association with visual field worsening in glaucoma patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247401
Author(s):  
Rukiye Aydın ◽  
Mine Barış ◽  
Ceren Durmaz-Engin ◽  
Lama A. Al-Aswad ◽  
Dana M. Blumberg ◽  
...  
Keyword(s):  
Experimental Data ◽  
Optic Nerve ◽  
Visual Field ◽  
Animal Models ◽  
Multivariate Logistic Regression Analysis ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Visual Field Defects ◽  
Control Group ◽  
Inner Plexiform Layer

Glaucoma is a chronic neurodegenerative disease of the optic nerve and a leading cause of irreversible blindness, worldwide. While the experimental research using animal models provides growing information about cellular and molecular processes, parallel analysis of the clinical presentation of glaucoma accelerates the translational progress towards improved understanding, treatment, and clinical testing of glaucoma. Optic nerve axon injury triggers early alterations of retinal ganglion cell (RGC) synapses with function deficits prior to manifest RGC loss in animal models of glaucoma. For testing the clinical relevance of experimental observations, this study analyzed the functional correlation of localized alterations in the inner plexiform layer (IPL), where RGCs establish synaptic connections with retinal bipolar and amacrine cells. Participants of the study included a retrospective cohort of 36 eyes with glaucoma and a control group of 18 non-glaucomatous subjects followed for two-years. The IPL was analyzed on consecutively collected macular SD-OCT scans, and functional correlations with corresponding 10–2 visual field scores were tested using generalized estimating equations (GEE) models. The GEE-estimated rate of decrease in IPL thickness (R = 0.36, P<0.001) and IPL density (R = 0.36, P<0.001), as opposed to unchanged or increased IPL thickness or density, was significantly associated with visual field worsening at corresponding analysis locations. Based on multivariate logistic regression analysis, this association was independent from the patients’ age, the baseline visual field scores, or the baseline thickness or alterations of retinal nerve fiber or RGC layers (P>0.05). These findings support early localized IPL alterations in correlation with progressing visual field defects in glaucomatous eyes. Considering the experimental data, glaucoma-related increase in IPL thickness/density might reflect dendritic remodeling, mitochondrial redistribution, and glial responses for synapse maintenance, but decreased IPL thickness/density might correspond to dendrite atrophy. The bridging of experimental data with clinical findings encourages further research along the translational path.

scholarly journals Substance P-immunoreactive neurons in hamster retinas

1999 ◽  
Vol 16 (3) ◽  
pp. 475-481 ◽  
Author(s):  
HAI-BIAO LI ◽  
KWOK-FAI SO ◽  
WAH CHEUK
Keyword(s):  
Optic Nerve ◽  
Substance P ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Inner Plexiform Layer ◽  
Nerve Section ◽  
Displaced Amacrine Cells ◽  
Contralateral Eye

Light-microscopic immunocytochemistry was utilized to localize the different populations of substance P-immunoreactive (SP-IR) neurons in the hamster retina. Based on observation of 2505 SP-IR neurons in transverse sections, 34% were amacrine cells whose pear-shaped or round cell bodies (7–8 μm) were situated in the inner half of the inner nuclear layer (INL) or in the inner plexiform layer (IPL), while 66% of SP-IR somata (6–20 μm) were located in the ganglion cell layer (GCL) which were interpreted to be displaced amacrine cells and retinal ganglion cells (RGCs). At least three types of SP-IR amacrine cells were identified. The SP-IR processes were distributed in strata 1, 3, and 5 with the densest plexus in stratum 5 of the inner plexiform layer. In the wholemounted retina, the SP-IR cells were found to be distributed throughout the entire retina and their mean number was estimated to be 4224 ± 76. Two experiments were performed to clarify whether any of the SP-IR neurons in the GCL were RGCs. The first experiment demonstrated the presence of SP-IR RGCs by retrogradely labeling the RGCs and subsequently staining the SP-IR cells in the retina using immunocytochemistry. The second experiment identified SP-IR central projections of RGCs to the contralateral dorsal lateral geniculate nucleus. This projection disappeared following removal of the contralateral eye. The number of SP-IR RGCs was estimated following optic nerve section. At 2 months after sectioning the optic nerve, the total number of SP-IR neurons in the GCL reduced from 4224 ± 76 to a mean of 1192 ± 139. Assuming that all SP-IR neurons in the GCL which disappeared after nerve section were RGCs, the number of SP-IR RGCs was estimated to be 3032, representing 3–4% of the total RGCs. In summary, findings of the present study provide evidence for the existence of SP-IR RGCs in the hamster retina.

scholarly journals Integrated electrophysiological evaluation in early normal-tension glaucoma

2016 ◽  
Vol 1 (2) ◽  
pp. 79-88
Author(s):  
Dario Messenio ◽  
Giuseppe Marano ◽  
Elia Biganzoli
Keyword(s):  
Optic Nerve ◽  
Visual Field ◽  
Evoked Potentials ◽  
Visual Evoked Potentials ◽  
Optic Nerve Head ◽  
Pattern Electroretinogram ◽  
Normal Subjects ◽  
Visual Field Defects ◽  
Control Group ◽  
Visual Evoked

Purpose: To evaluate the variations of intraocular pressure (IOP), morphometric optic nerve head characteristic, perimetric indices and electrophysiological parameters (pattern electroretinogram and visual evoked potentials) before and after topical IOP lowering in patients with early normal-tension glaucoma.Methods: we evaluated 38 eyes of 20 patients with IOP < 21 mmHg, initial glaucomatous optic neuropathy (valued with HRT: retinal nerve fiber layer thickness (RNFL) and linear cup/disk ratio (linear C/D ratio)), minimal visual field defects (Octopus 101: G2 program), best correct visual acuity more than 15/20 and pathological electrophysiological parameters (valued with pattern electroretinogram (PERG) and visual evoked potentials (VEPs)), free of systemic or other ocular diseases. All parameters were evaluated at the beginning of the study (T0) and after 12 months of therapy (T12). A randomized normal control group (27 eyes of 14 subjects) with apparent larger disc cupping underwent all exams at initial of study (T0) and after 12 months (T12).Results: Among electrophysiological parameters, at the beginning of the study NTG P100 VEPs latency is slightly increased and P100 amplitude is reduced compared to normal subjects. There are not significant variations after 12 months. P50 PERG latency in NTG is quite similar respect normal and do not modify after therapy. P50N95 complex PERG amplitude in NTG is reduced compared to normal subjects and slightly increases after 12 months (1.8 vs 1.5 ; 2.4 vs 1.9 micronvolts, with different checkboard spatial frequency). Cortical retinal time (CRT) is slightly delayed in NTG and does not modify. Among visual field indices, MD and CLV is slightly higher in NTG and do not significantly modify after therapy. Among morphometric optic nerve head characteristics, linear C/D and RNFL thickness are quite similar in NTG and do not modify. IOP is quite similar between NTG and control group and modifies in NTG after therapy.Conclusion: In a viewpoint of an integrated diagnostic, electrophysiological tests (VEPs and PERG) could provide a more sensitive measure of retinal ganglion cell integrity and help to distinguish between early normal-pressure glaucoma patients with no or minimal visual field alterations and normal subjects with apparent larger disc cupping.

scholarly journals Blue light blind-spot stimulation upregulates b-wave and pattern ERG activity in myopes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Amorim-de-Sousa ◽  
Tim Schilling ◽  
Paulo Fernandes ◽  
Yeshwanth Seshadri ◽  
Hamed Bahmani ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Electrical Activity ◽  
Blue Light ◽  
Optic Nerve Head ◽  
Plexiform Layer ◽  
Pattern Electroretinogram ◽  
Blind Spot ◽  
Inner Plexiform Layer ◽  
Pattern Erg ◽  
Myopia Progression

AbstractUpregulation of retinal dopaminergic activity may be a target treatment for myopia progression. This study aimed to explore the viability of inducing changes in retinal electrical activity with short-wavelength light targeting melanopsin-expressing retinal ganglion cells (ipRGCs) passing through the optic nerve head. Fifteen healthy non-myopic or myopic young adults were recruited and underwent stimulation with blue light using a virtual reality headset device. Amplitudes and implicit times from photopic 3.0 b-wave and pattern electroretinogram (PERG) were measured at baseline and 10 and 20 min after stimulation. Relative changes were compared between non-myopes and myopes. The ERG b-wave amplitude was significantly larger 20 min after blind-spot stimulation compared to baseline (p < 0.001) and 10 min (p < 0.001) post-stimulation. PERG amplitude P50-N95 also showed a significant main effect for ‘Time after stimulation’ (p < 0.050). Implicit times showed no differences following blind-spot stimulation. PERG and b-wave changes after blind-spot stimulation were stronger in myopes than non-myopes. It is possible to induce significant changes in retinal electrical activity by stimulating ipRGCs axons at the optic nerve head with blue light. The results suggest that the changes in retinal electrical activity are located at the inner plexiform layer and are likely to involve the dopaminergic system.

scholarly journals Inner and outer retinal layer thickness alterations in pediatric and juvenile craniopharyngioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ga-In Lee ◽  
Kyung-Ah Park ◽  
Sei Yeul Oh ◽  
Doo-Sik Kong ◽  
Sang Duk Hong
Keyword(s):  
Layer Thickness ◽  
Outer Nuclear Layer ◽  
Plexiform Layer ◽  
Visual Field Defects ◽  
Retinal Layer ◽  
Inner Plexiform Layer ◽  
Healthy Controls ◽  
Fiber Layer ◽  
Photoreceptor Layer ◽  
Chiasmal Compression

AbstractWe evaluated postoperative retinal thickness in pediatric and juvenile craniopharyngioma (CP) patients with chiasmal compression using optical coherence tomography (OCT) auto-segmentation. We included 18 eyes of 18 pediatric or juvenile patients with CP and 20 healthy controls. Each thickness of the macular retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer was compared between the CP patients and healthy controls. There was significant thinning in the macular RNFL (estimates [μm], superior, − 10.68; inferior, − 7.24; nasal, − 14.22), all quadrants of GCL (superior, − 16.53; inferior, − 14.37; nasal, − 24.34; temporal, − 9.91) and IPL (superior, − 11.45; inferior, − 9.76; nasal, − 15.25; temporal, − 4.97) in pediatric and juvenile CP patients postoperatively compared to healthy control eyes after adjusting for age and refractive errors. Thickness reduction in the average and nasal quadrant of RNFL, GCL, and IPL was associated with peripapillary RNFL thickness, and reduced nasal quadrant GCL and IPL thicknesses were associated with postoperative visual field defects. In pediatric and juvenile patients with CP, decreased inner retinal layer thickness following chiasmal compression was observed. The changes in retinal structures were closely related to peripapillary RNFL thinning and functional outcomes.

Multiple cell targets for melatonin action in Xenopus laevis retina: Distribution of melatonin receptor immunoreactivity

2001 ◽  
Vol 18 (5) ◽  
pp. 695-702 ◽  
Author(s):  
ALLAN F. WIECHMANN ◽  
CELESTE R. WIRSIG-WIECHMANN
Keyword(s):  
Xenopus Laevis ◽  
Direct Action ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Receptor Protein ◽  
Inner Plexiform Layer ◽  
Melatonin Receptor ◽  
Multiple Cell

In the retina of the African clawed frog (Xenopus laevis), melatonin is synthesized by the photoreceptors at night, and binds to receptors that likely mediate paracrine responses. Melatonin appears to alter the sensitivity of the retinal cells to light, and may play a key role in regulating important circadian events that occur in the eye. A polyclonal antibody was raised against a 13 amino acid peptide corresponding to a region of the third cytoplasmic loop of the Xenopus laevis Mel1c melatonin receptor. Western blot analysis revealed a major immunoreactive band of approximately 60 kD in neural retina and retinal pigment epithelium (RPE) membranes. Immunocytochemical labeling of sections of Xenopus eyes demonstrated intense melatonin receptor-like immunoreactivity in the inner plexiform layer (IPL). Immunolabeling with antibodies to glutamate decarboxylase (GAD) or tyrosine hydroxylase (TOH) appeared to co-localize with the melatonin receptor immunoreactivity in different sublaminas of the IPL. This suggests that both GABAergic and dopaminergic amacrine cells express melatonin receptor protein. There were also some melatonin receptor immunoreactive varicose fibers in the IPL that did not co-localize with either TOH or GAD, and may represent efferent fibers, since they could be followed into the optic nerve. Melatonin receptor immunoreactivity was also present on cell soma in the ganglion cell layer. Furthermore, a moderate level of melatonin receptor immunoreactivity was observed in the RPE and rod and cone photoreceptor cells. The presence of melatonin receptor immunoreactivity in these cells supports previous observations of melatonin receptor RNA expression in multiple cell types in the Xenopus retina. Expression of melatonin receptor protein in the photoreceptors suggests that melatonin may have a direct action on these cells.

Membrane currents evoked by ionotropic glutamate receptor agonists in rod bipolar cells in the rat retinal slice preparation

1996 ◽  
Vol 76 (1) ◽  
pp. 401-422 ◽  
Author(s):  
E. Hartveit
Keyword(s):  
Nmda Receptor ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Receptor Agonists ◽  
Long Latency ◽  
Glutamate Receptor Agonists ◽  
Conductance Increase ◽  
Rod Bipolar Cells

1. With the use of the whole cell voltage-clamp technique, I have recorded the current responses to ionotropic glutamate receptor agonists of rod bipolar cells in vertical slices of rat retina. Rod bipolar cells constitute a single population of cells and were visualized by infrared differential interference contrast video microscopy. They were targeted by the position of their cell bodies in the inner nuclear layer and, after recording, were visualized in their entirety by labeling with the fluorescent dye Lucifer yellow, which was included in the recording pipette. To study current-voltage relationships of evoked currents, voltage-gated potassium currents were blocked by including Cs+ and tetraethylammonium+ in the recording pipette. 2. Pressure application of the non-N-methyl-D-aspartate (non-NMDA) receptor agonists kainate and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) from puffer pipettes evoked a long-latency conductance increase selective for chloride ions. When the intracellular chloride concentration was increased, the reversal potential changed, corresponding to the change in equilibrium potential for chloride. The response was evoked in the presence of 5 mM Co2+ and nominally O mM Ca2+ in the extracellular solution, presumably blocking all external Ca2(+)-dependent release of neurotransmitter. 3. The long latency of kainate-evoked currents in bipolar cells contrasted with the short-latency currents evoked by gamma-aminobutyric acid (GABA) and glycine in rod bipolar cells and by kainate in amacrine cells. 4. Application of NMDA evoked no response in rod bipolar cells. 5. Coapplication of AMPA with cyclothiazide, a blocker of agonist-evoked desensitization of AMPA receptors, enhanced the conductance increase compared with application of AMPA alone. Coapplication of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione blocked the response to kainate and AMPA, indicating that the response was mediated by conventional ionotropic glutamate receptors. 6. The conductance increase evoked by non-NMDA receptor agonists could not be blocked by a combination of 100 microM picrotoxin and 10 microM strychnine. Application of the GABAC receptor antagonist 3-aminopropyl (methyl)phosphinic acid (3-APMPA) strongly reduced the response, and coapplication of 500 microM 3-APMPA and 100 microM picrotoxin completely blocked the response. These results suggested that the conductance increase evoked by non-NMDA receptor agonists was mediated by release of GABA and activation of GABAC receptors, and most likely also GABAA receptors, on rod bipolar cells. 7. Kainate responses like those described above could not be evoked in bipolar cells in which the axon had been cut somewhere along its passage to the inner plexiform layer during the slicing procedure. This suggests that the response was dependent on the integrity of the axon terminal in the inner plexiform layer, known to receive GABAergic synaptic input from amacrine cells. 8. The results indicate that ionotropic glutamate receptors are not involved in mediating synaptic input from photoreceptors to rod bipolar cells and that an unconventional mechanism of GABA release from amacrine cells might operate in the inner plexiform layer.

A coupled network for parasol but not midget ganglion cells in the primate retina

1992 ◽  
Vol 9 (3-4) ◽  
pp. 279-290 ◽  
Author(s):  
Dennis M. Dacey ◽  
Sarah Brace
Keyword(s):  
Nearest Neighbor ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Distinct Pattern ◽  
Field Size ◽  
Inner Plexiform Layer ◽  
Dendritic Field

AbstractIntracellular injections of Neurobiotin were used to determine whether the major ganglion cell classes of the macaque monkey retina, the magnocellular-projecting parasol, and the parvocellular-projecting midget cells showed evidence of cellular coupling similar to that recently described for cat retinal ganglion cells. Ganglion cells were labeled with the fluorescent dye acridine orange in an in vitro, isolated retina preparation and were selectively targeted for intracellular injection under direct microscopic control. The macaque midget cells, like the beta cells of the cat's retina, showed no evidence of tracer coupling when injected with Neurobiotin. By contrast, Neurobiotin-filled parasol cells, like cat alpha cells, showed a distinct pattern of tracer coupling to each other (homotypic coupling) and to amacrine cells (heterotypic coupling).In instances of homotypic coupling, the injected parasol cell was surrounded by a regular array of 3–6 neighboring parasol cells. The somata and proximal dendrites of these tracer-coupled cells were lightly labeled and appeared to costratify with the injected cell. Analysis of the nearest-neighbor distances for the parasol cell clusters showed that dendritic-field overlap remained constant as dendritic-field size increased from 100–400 μm in diameter.At least two amacrine cell types showed tracer coupling to parasol cells. One amacrine type had a small soma and thin, sparsely branching dendrites that extended for 1–2 mm in the inner plexiform layer. A second amacrine type had a relatively large soma, thick main dendrites, and distinct, axon-like processes that extended for at least 2–3 mm in the inner plexiform layer. The main dendrites of the large amacrine cells were closely apposed to the dendrites of parasol cells and may be the site of Neurobiotin transfer between the two cell types. We suggest that the tracer coupling between neighboring parasol cells takes place indirectly via the dendrites of the large amacrine cells and provides a mechanism, absent in midget cells, for increasing parasol cell receptive-field size and luminance contrast sensitivity.

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