scholarly journals Melanopsin expression in the cornea

2018 ◽  
Vol 35 ◽  
Author(s):  
ANTON DELWIG ◽  
SHAWNTA Y. CHANEY ◽  
ANDREA S. BERTKE ◽  
JAN VERWEIJ ◽  
SUSANA QUIRCE ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Nerve Fibers ◽  
Visual Signals ◽  
Light Responses ◽  
Rods And Cones ◽  
Retinal Tissue ◽  
Antibody Staining ◽  
Electrophysiological Recordings ◽  
Pupil Constriction ◽  
Sensory Fibers

AbstractA unique class of intrinsically photosensitive retinal ganglion cells in mammalian retinae has been recently discovered and characterized. These neurons can generate visual signals in the absence of inputs from rods and cones, the conventional photoreceptors in the visual system. These light sensitive ganglion cells (mRGCs) express the non-rod, non-cone photopigment melanopsin and play well documented roles in modulating pupil responses to light, photoentrainment of circadian rhythms, mood, sleep and other adaptive light functions. While most research efforts in mammals have focused on mRGCs in retina, recent studies reveal that melanopsin is expressed in non-retinal tissues. For example, light-evoked melanopsin activation in extra retinal tissue regulates pupil constriction in the iris and vasodilation in the vasculature of the heart and tail. As another example of nonretinal melanopsin expression we report here the previously unrecognized localization of this photopigment in nerve fibers within the cornea. Surprisingly, we were unable to detect light responses in the melanopsin-expressing corneal fibers in spite of our histological evidence based on genetically driven markers and antibody staining. We tested further for melanopsin localization in cell bodies of the trigeminal ganglia (TG), the principal nuclei of the peripheral nervous system that project sensory fibers to the cornea, and found expression of melanopsin mRNA in a subset of TG neurons. However, neither electrophysiological recordings nor calcium imaging revealed any light responsiveness in the melanopsin positive TG neurons. Given that we found no light-evoked activation of melanopsin-expressing fibers in cornea or in cell bodies in the TG, we propose that melanopsin protein might serve other sensory functions in the cornea. One justification for this idea is that melanopsin expressed in Drosophila photoreceptors can serve as a temperature sensor.

scholarly journals Intrinsic and Extrinsic Light Responses in Melanopsin-Expressing Ganglion Cells During Mouse Development

2008 ◽  
Vol 100 (1) ◽  
pp. 371-384 ◽  
Author(s):  
Tiffany M. Schmidt ◽  
Kenichiro Taniguchi ◽  
Paulo Kofuji
Keyword(s):  
Fluorescent Protein ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Artificial Chromosome ◽  
Inner Plexiform Layer ◽  
Mouse Development ◽  
Light Responses ◽  
Functional Changes ◽  
Electrophysiological Recordings ◽  
Green Fluorescent

Melanopsin (Opn4) is a photopigment found in a subset of retinal ganglion cells (RGCs) that project to various brain areas. These neurons are intrinsically photosensitive (ipRGCs) and are implicated in nonimage-forming responses to environmental light such as the pupillary light reflex and circadian entrainment. Recent evidence indicates that ipRGCs respond to light at birth, but questions remain as to whether and when they undergo significant functional changes. We used bacterial artificial chromosome transgenesis to engineer a mouse line in which enhanced green fluorescent protein (EGFP) is expressed under the control of the melanopsin promoter. Double immunolabeling for EGFP and melanopsin demonstrates their colocalization in ganglion cells of mutant mouse retinas. Electrophysiological recordings of ipRGCs in neonatal mice (postnatal day 0 [P0] to P7) demonstrated that these cells responded to light with small and sluggish depolarization. However, starting at P11 we observed ipRGCs that responded to light with a larger and faster onset (<1 s) and offset (<1 s) depolarization. These faster, larger depolarizations were observed in most ipRGCs by early adult ages. However, on application of a cocktail of synaptic blockers, we found that all cells responded to light with slow onset (>2.5 s) and offset (>10 s) depolarization, revealing the intrinsic, melanopsin-mediated light responses. The extrinsic, cone/rod influence on ipRGCs correlates with their extensive dendritic stratification in the inner plexiform layer. Collectively, these results demonstrate that ipRGCs make use of melanopsin for phototransduction before eye opening and that these cells further integrate signals derived from the outer retina as the retina matures.

scholarly journals Nerve fibers in culture and their interactions with non-neural cells visualized by immunofluorescence.

1979 ◽  
Vol 80 (3) ◽  
pp. 629-641 ◽  
Author(s):  
H Jockusch ◽  
B M Jockusch ◽  
M M Burger
Keyword(s):  
Spinal Cord ◽  
Ganglion Cells ◽  
Cell Types ◽  
Nerve Fibers ◽  
Affinity Column ◽  
Neural Cells ◽  
Embryonic Mouse ◽  
Antibody Staining ◽  
Order Of Magnitude ◽  
Nerve Muscle

Cultures of embryonic mouse spinal cord explants, alone or in combination with rat myotubes, were stained by indirect immunofluorescence using antibodies against three structural proteins to: (a) reveal the distribution of these proteins among different cell types, and (b) test the usefulness of antibody staining to reveal the gross morphology of the neurite network in complex cultures. Affinity column purified antibodies were used against chicken gizzard actin, porcine brain tubulin, and skeletal muscle alpha-actinin. Neurites were stained intensely by anti-actin as was the stress fiber pattern of underlying fibroblasts. With anti-tubulin, the staining of neurites was an order of magnitude more intense than the staining of the microtubule pattern of background fibroblasts. Neurite cell bodies and astrocyte-like glia cells were stained with anti-tubulin and their nuclei remained unstained. Anti-tubulin could thus be used to trace even the finest extensions of nerve processes in spinal cord and spinal cord-muscle cultures. Furthermore, it could be combined with the histochemical reaction for acetylcholinesterase (AChE, EC 3.1.1.7) to demonstrate AChE-positive neurons and specialized nerve-muscle contact sites. The staining of neural elements with anti-alpha-actinin was generally much weaker than with anti-actin and anti-tubulin. Neurites were stained only moderately in comparison to myotube Z lines in the same culture. However, a distinct staining of the periphery of dorsal root ganglion cells was observed. Thus, a protein immunologically related to muscle alpha-actinin is present in the nervous system. In myotubes, Z lines were stained intensely with anti-alpha-actinin while I bands were only faintly stained with anti-actin. In isolated myofibrils, both structures were stained intensely with the same antibody preparations.

scholarly journals Melanopsin Carboxy-terminus Phosphorylation Plasticity and Bulk Negative Charge, not Strict Site Specificity, Achieves Phototransduction Deactivation

2020 ◽  
Author(s):  
Juan C. Valdez-Lopez ◽  
Sahil Gulati ◽  
Elelbin A. Ortiz ◽  
Krzysztof Palczewski ◽  
Phyllis R. Robinson
Keyword(s):  
Ganglion Cells ◽  
Proximal Region ◽  
Hek293 Cells ◽  
Small Subset ◽  
Phosphorylation Sites ◽  
Carboxy Terminus ◽  
Light Responses ◽  
Protein Receptor ◽  
C Terminus ◽  
Pupil Constriction

ABSTRACTMelanopsin is a visual pigment expressed in a small subset of ganglion cells in the mammalian retina known as intrinsically photosensitive retinal ganglion cells (ipRGCs) and is implicated in regulating non-image forming functions such as circadian photoentrainment and pupil constriction and contrast sensitivity in image formation. Mouse melanopsin’s Carboxy-terminus (C-terminus) possesses 38 serine and threonine residues, which can potentially serve as phosphorylation sites for a G-protein Receptor Kinase (GRK) and be involved in the deactivation of signal transduction. Previous studies suggest that S388, T389, S391, S392, S394, S395 on the proximal region of the C-terminus of mouse melanopsin are necessary for melanopsin deactivation. We expressed a series of mouse melanopsin C-terminal mutants in HEK293 cells and using calcium imaging, and we found that the necessary cluster of six serine and threonine residues, while being critical, are insufficient for proper melanopsin deactivation. Interestingly, the additional six serine and threonine residues adjacent to the required six sites, in either proximal or distal direction, are capable of restoring wild-type deactivation of melanopsin. These findings suggest an element of plasticity in the molecular basis of melanopsin phosphorylation and deactivation. In addition, C-terminal chimeric mutants and molecular modeling studies support the idea that the initial steps of deactivation and β-arrestin binding are centered around these critical phosphorylation sites (S388-S395). This degree of functional versatility could help explain the diverse ipRGC light responses as well as non-image and image forming behaviors, even though all six sub types of ipRGCs express the same melanopsin gene OPN4.

scholarly journals Mapping nonlinear receptive field structure in primate retina at single cone resolution

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Jeremy Freeman ◽  
Greg D Field ◽  
Peter H Li ◽  
Martin Greschner ◽  
Deborah E Gunning ◽  
...  
Keyword(s):  
Large Scale ◽  
Neural Circuit ◽  
Visual Stimulation ◽  
Ganglion Cells ◽  
Single Cells ◽  
Visual Signals ◽  
Cell Type ◽  
Light Responses ◽  
Single Cone ◽  
Model Components

The function of a neural circuit is shaped by the computations performed by its interneurons, which in many cases are not easily accessible to experimental investigation. Here, we elucidate the transformation of visual signals flowing from the input to the output of the primate retina, using a combination of large-scale multi-electrode recordings from an identified ganglion cell type, visual stimulation targeted at individual cone photoreceptors, and a hierarchical computational model. The results reveal nonlinear subunits in the circuity of OFF midget ganglion cells, which subserve high-resolution vision. The model explains light responses to a variety of stimuli more accurately than a linear model, including stimuli targeted to cones within and across subunits. The recovered model components are consistent with known anatomical organization of midget bipolar interneurons. These results reveal the spatial structure of linear and nonlinear encoding, at the resolution of single cells and at the scale of complete circuits.

scholarly journals Melanopsin- and L-cone–induced pupil constriction is inhibited by S- and M-cones in humans

2018 ◽  
Vol 115 (4) ◽  
pp. 792-797 ◽  
Author(s):  
Tom Woelders ◽  
Thomas Leenheers ◽  
Marijke C. M. Gordijn ◽  
Roelof A. Hut ◽  
Domien G. M. Beersma ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Brightness Discrimination ◽  
Light Response ◽  
Inhibitory Input ◽  
Human Retina ◽  
Constant Intensity ◽  
Light Responses ◽  
Pupillary Light ◽  
Pupillary Constriction ◽  
Pupil Constriction

The human retina contains five photoreceptor types: rods; short (S)-, mid (M)-, and long (L)-wavelength–sensitive cones; and melanopsin-expressing ganglion cells. Recently, it has been shown that selective increments in M-cone activation are paradoxically perceived as brightness decrements, as opposed to L-cone increments. Here we show that similar effects are also observed in the pupillary light response, whereby M-cone or S-cone increments lead to pupil dilation whereas L-cone or melanopic illuminance increments resulted in pupil constriction. Additionally, intermittent photoreceptor activation increased pupil constriction over a 30-min interval. Modulation of L-cone or melanopic illuminance within the 0.25–4-Hz frequency range resulted in more sustained pupillary constriction than light of constant intensity. Opposite results were found for S-cone and M-cone modulations (2 Hz), mirroring the dichotomy observed in the transient responses. The transient and sustained pupillary light responses therefore suggest that S- and M-cones provide inhibitory input to the pupillary control system when selectively activated, whereas L-cones and melanopsin response fulfill an excitatory role. These findings provide insight into functional networks in the human retina and the effect of color-coding in nonvisual responses to light, and imply that nonvisual and visual brightness discrimination may share a common pathway that starts in the retina.

scholarly journals Changes in physiological properties of rat ganglion cells during retinal degeneration

2011 ◽  
Vol 105 (5) ◽  
pp. 2560-2571 ◽  
Author(s):  
Chris Sekirnjak ◽  
Lauren H. Jepson ◽  
Pawel Hottowy ◽  
Alexander Sher ◽  
Wladyslaw Dabrowski ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Time Course ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Similar Rate ◽  
Visual Signals ◽  
Light Responses ◽  
Functional Changes ◽  
Physiological Properties

Retinitis pigmentosa (RP) is a leading cause of degenerative vision loss, yet its progressive effects on visual signals transmitted from the retina to the brain are not well understood. The transgenic P23H rat is a valuable model of human autosomal dominant RP, exhibiting extensive similarities to the human disease pathology, time course, and electrophysiology. In this study, we examined the physiological effects of degeneration in retinal ganglion cells (RGCs) of P23H rats aged between P37 and P752, and compared them with data from wild-type control animals. The strength and the size of visual receptive fields of RGCs decreased rapidly with age in P23H retinas. Light responses mediated by rod photoreceptors declined earlier (∼P300) than cone-mediated light responses (∼P600). Responses of ON and OFF RGCs diminished at a similar rate. However, OFF cells exhibited hyperactivity during degeneration, whereas ON cells showed a decrease in firing rate. The application of synaptic blockers abolished about half of the elevated firing in OFF RGCs, indicating that the remodeled circuitry was not the only source of degeneration-induced hyperactivity. These results advance our understanding of the functional changes associated with retinal degeneration.

Melatonin As a Modulator of Degenerative and Regenerative Signaling Pathways in Injured Retinal Ganglion Cells

2019 ◽  
Vol 25 (28) ◽  
pp. 3057-3073 ◽  
Author(s):  
Kobra B. Juybari ◽  
Azam Hosseinzadeh ◽  
Habib Ghaznavi ◽  
Mahboobeh Kamali ◽  
Ahad Sedaghat ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Ganglion Cells ◽  
Axon Growth ◽  
Nerve Fibers ◽  
Retinal Ganglion

Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.

Amacrine and ganglion cell contributions to the electroretinogram in amphibian retina

2001 ◽  
Vol 18 (1) ◽  
pp. 147-156 ◽  
Author(s):  
GAUTAM AWATRAMANI ◽  
JUE WANG ◽  
MALCOLM M. SLAUGHTER
Keyword(s):  
Contrast Agents ◽  
Ganglion Cell ◽  
Neuronal Activity ◽  
Opposite Effect ◽  
Cell Function ◽  
Ganglion Cells ◽  
Field Potential ◽  
Tiger Salamander ◽  
Third Order ◽  
Light Responses

The neuronal generators of the b- and d-waves of the electroretinogram (ERG) were investigated in the tiger salamander retina to determine if amacrine and ganglion cells contribute to this field potential. Several agents were used that affect third-order neurons, such as tetrodotoxin, baclofen, and NMDA agonists and antagonists. Baclofen, an agent that enhances light responses in third-order neurons, increased the d-wave and reduced the b-wave. In contrast, agents that decrease light responses in third-order neurons had the opposite effect of enhancing the b-wave and depressing the d-wave. The effect on the d-wave was particularly pronounced. The results indicate that third-order neuronal activity influences b- and d-waves of the ERG. The opposing actions suggest that the b-wave to d-wave ratio might serve as an measure of ganglion cell function.

Electron Microscopic Findings in Presbycusic Degeneration of the Basal Turn of the Human Cochlea

1979 ◽  
Vol 87 (6) ◽  
pp. 818-836 ◽  
Author(s):  
Joseph B. Nadol
Keyword(s):  
Light Microscopy ◽  
Hair Cells ◽  
Basilar Membrane ◽  
Ganglion Cells ◽  
Nerve Fibers ◽  
Degenerative Changes ◽  
Supporting Cells ◽  
Neural Degeneration ◽  
Basal Turn ◽  
Temporal Bones

Three human temporal bones with presbycusis affecting the basal turn of the cochlea were studied by light and electron microscopy. Conditions in two ears examined by light microscopy were typical of primary neural degeneration, with a descending audiometric pattern, loss of cochlear neurons in the basal turn, and preservation of the organ of Corti. Ultrastructural analysis revealed normal hair cells and marked degenerative changes of the remaining neural fibers, especially in the basal turn. These changes included a decrease in the number of synapses at the base of hair cells, accumulation of cellular debris in the spiral bundles, abnormalities of the dendritic fibers and their sheaths in the osseous spiral lamina, and degenerative changes in the spiral ganglion cells and axons. These changes were interpreted as an intermediate stage of degeneration prior to total loss of nerve fibers and ganglion cells as visualized by light microscopy. In the third ear the changes observed were typical of primary degeneration of hair and supporting cells in the basal turn with secondary neural degeneration. Additional observations at an ultrastructural level included maintenance of the tight junctions of the scala media despite loss of both hair and supporting cells, suggesting a capacity for cellular “healing” in the inner ear. Degenerative changes were found in the remaining neural fibers in the osseous spiral lamina. In addition, there was marked thickening of the basilar membrane in the basal turn, which consisted of an increased number of fibrils and an accumulation of amorphous osmiophilic material in the basilar membrane. This finding supports the concept that mechanical alterations may occur in presbycusis of the basal turn.

scholarly journals The visual ecology of a deep-sea fish, the escolar Lepidocybium flavobrunneum (Smith, 1843)

2014 ◽  
Vol 369 (1636) ◽  
pp. 20130039 ◽  
Author(s):  
Eva Landgren ◽  
Kerstin Fritsches ◽  
Richard Brill ◽  
Eric Warrant
Keyword(s):  
Surface Waters ◽  
Deep Sea ◽  
Ganglion Cells ◽  
Optical Path Length ◽  
Predatory Fish ◽  
Flicker Fusion Frequency ◽  
Optical Sensitivity ◽  
Light Levels ◽  
Electrophysiological Recordings ◽  
Maximal Absorption

Escolar ( Lepidocybium flavobrunneum , family Gempylidae) are large and darkly coloured deep-sea predatory fish found in the cold depths (more than 200 m) during the day and in warm surface waters at night. They have large eyes and an overall low density of retinal ganglion cells that endow them with a very high optical sensitivity. Escolar have banked retinae comprising six to eight layers of rods to increase the optical path length for maximal absorption of the incoming light. Their retinae possess two main areae of higher ganglion cell density, one in the ventral retina viewing the dorsal world above (with a moderate acuity of 4.6 cycles deg −1 ), and the second in the temporal retina viewing the frontal world ahead. Electrophysiological recordings of the flicker fusion frequency (FFF) in isolated retinas indicate that escolar have slow vision, with maximal FFF at the highest light levels and temperatures (around 9 Hz at 23°C) which fall to 1–2 Hz in dim light or cooler temperatures. Our results suggest that escolar are slowly moving sit-and-wait predators. In dim, warm surface waters at night, their slow vision, moderate dorsal resolution and highly sensitive eyes may allow them to surprise prey from below that are silhouetted in the downwelling light.

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