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Progress in Retinal and Eye Research Sep 2015Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The... (Review)
Review
Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons.
Topics: Fixatives; Formaldehyde; Humans; Immunohistochemistry; Osmolar Concentration; Retina; Retinal Neurons; Staining and Labeling; Tissue Fixation
PubMed: 25892361
DOI: 10.1016/j.preteyeres.2015.04.001 -
Current Biology : CB Apr 2022In the vertebrate eye, photoreceptors are covered beneath a thick sheet of neural retina and face away from the light. This seemingly awkward arrangement has led to the...
In the vertebrate eye, photoreceptors are covered beneath a thick sheet of neural retina and face away from the light. This seemingly awkward arrangement has led to the popular notion that our retinas are upside down, implying a deep design flaw. Baden and Nilsson argue that, from an evolutionary perspective, an inverted design actually offers many notable benefits that might have never been exploited if things had started off the other way round.
Topics: Face; Photoreceptor Cells; Retina
PubMed: 35413251
DOI: 10.1016/j.cub.2022.02.065 -
Biomolecules Jul 2022Photoreceptors are sensitive neuronal cells with great metabolic demands, as they are responsible for carrying out visual phototransduction, a complex and multistep... (Review)
Review
Photoreceptors are sensitive neuronal cells with great metabolic demands, as they are responsible for carrying out visual phototransduction, a complex and multistep process that requires the exquisite coordination of a large number of signalling protein components. Therefore, the viability of photoreceptors relies on mechanisms that ensure a well-balanced and functional proteome that maintains the protein homeostasis, or proteostasis, of the cell. This review explores how the different isoforms of Hsp90, including the cytosolic Hsp90α/β, the mitochondrial TRAP1, and the ER-specific GRP94, are involved in the different proteostatic mechanisms of photoreceptors, and elaborates on Hsp90 function when retinal homeostasis is disturbed. In addition, several studies have shown that chemical manipulation of Hsp90 has significant consequences, both in healthy and degenerating retinae, and this can be partially attributed to the fact that Hsp90 interacts with important photoreceptor-associated client proteins. Here, the interaction of Hsp90 with the retina-specific client proteins PDE6 and GRK1 will be further discussed, providing additional insights for the role of Hsp90 in retinal disease.
Topics: HSP90 Heat-Shock Proteins; Humans; Photoreceptor Cells; Proteostasis; Retina
PubMed: 35883534
DOI: 10.3390/biom12070978 -
Frontiers in Neural Circuits 2018Visual information is already processed in the retina before it is transmitted to higher visual centers in the brain. This includes the extraction of salient features... (Review)
Review
Visual information is already processed in the retina before it is transmitted to higher visual centers in the brain. This includes the extraction of salient features from visual scenes, such as motion directionality or contrast, through neurons belonging to distinct neural circuits. Some retinal neurons are tuned to the orientation of elongated visual stimuli. Such 'orientation-selective' neurons are present in the retinae of most, if not all, vertebrate species analyzed to date, with species-specific differences in frequency and degree of tuning. In some cases, orientation-selective neurons have very stereotyped functional and morphological properties suggesting that they represent distinct cell types. In this review, we describe the retinal cell types underlying orientation selectivity found in various vertebrate species, and highlight their commonalities and differences. In addition, we discuss recent studies that revealed the cellular, synaptic and circuit mechanisms at the basis of retinal orientation selectivity. Finally, we outline the significance of these findings in shaping our current understanding of how this fundamental neural computation is implemented in the visual systems of vertebrates.
Topics: Animals; Humans; Orientation; Retina; Visual Pathways
PubMed: 29467629
DOI: 10.3389/fncir.2018.00011 -
The Journal of Physiology Jun 2009Functional architecture of the striate cortex is known mostly at the tissue level--how neurons of different function distribute across its depth and surface on a scale... (Review)
Review
Functional architecture of the striate cortex is known mostly at the tissue level--how neurons of different function distribute across its depth and surface on a scale of millimetres. But explanations for its design--why it is just so--need to be addressed at the synaptic level, a much finer scale where the basic description is still lacking. Functional architecture of the retina is known from the scale of millimetres down to nanometres, so we have sought explanations for various aspects of its design. Here we review several aspects of the retina's functional architecture and find that all seem governed by a single principle: represent the most information for the least cost in space and energy. Specifically: (i) why are OFF ganglion cells more numerous than ON cells? Because natural scenes contain more negative than positive contrasts, and the retina matches its neural resources to represent them equally well; (ii) why do ganglion cells of a given type overlap their dendrites to achieve 3-fold coverage? Because this maximizes total information represented by the array--balancing signal-to-noise improvement against increased redundancy; (iii) why do ganglion cells form multiple arrays? Because this allows most information to be sent at lower rates, decreasing the space and energy costs for sending a given amount of information. This broad principle, operating at higher levels, probably contributes to the brain's immense computational efficiency.
Topics: Algorithms; Animals; Axons; Dendrites; Electrophysiology; Humans; Optic Nerve; Retina; Retinal Ganglion Cells; Synapses; Visual Fields; Visual Pathways
PubMed: 19525561
DOI: 10.1113/jphysiol.2009.170704 -
Investigative Ophthalmology & Visual... Sep 2023Keratin 8/18 (KRT8/18), paired members of the intermediate filament family, have shown vital functions in regulating physiological activities more than supporting the...
PURPOSE
Keratin 8/18 (KRT8/18), paired members of the intermediate filament family, have shown vital functions in regulating physiological activities more than supporting the mechanic strength for cells and organelles. However, the KRT8/18 presence in retinal ganglion cells (RGCs) and functions on neuroprotection in a mouse model of acute ocular hypertension (AOH) are unknown and worthy of exploration.
METHODS
We identified the existence of KRT8/18 in normal human and mouse retinas and primary RGCs. KRT8/18 levels were detected after AOH modeling. The adeno-associated virus (AAV) system was intravitreally used for selective KRT8 knockdown in RGCs. The histological changes, the loss and dysfunction of RGCs, and the gliosis in retinas were detected. The markers of cell apoptosis and MAPK pathways were investigated.
RESULTS
KRT8/18 existed in all retinal layers and was highly expressed in RGCs, and they increased after AOH induction. The KRT8 knockdown in RGCs caused no histopathological changes and RGC loss in retinas without AOH modeling. However, after the KRT8 deficiency, AOH significantly promoted the loss of whole retina and inner retina thickness, the reduction, apoptosis, and dysfunction of RGCs, and the glial activation. Besides, downregulated Bcl-2 and upregulated cleaved-Caspase 3 were found in the AOH retinas with KRT8 knockdown, which may be caused by the increased phosphorylation level of MAPK pathways (JNK, p38, and ERK).
CONCLUSIONS
The KRT8 deficiency promoted RGC apoptosis and neurodegeneration by abnormal activation of MAPK pathways in AOH retinas. Targeting KRT8 may serve as a novel treatment for saving RCGs from glaucomatous injuries.
Topics: Animals; Humans; Mice; Apoptosis; Glaucoma; Ocular Hypertension; Retina; Retinal Ganglion Cells
PubMed: 37656477
DOI: 10.1167/iovs.64.12.1 -
The Journal of Physiology Aug 2017Butterflies use colour vision when searching for flowers. Unlike the trichromatic retinas of humans (blue, green and red cones; plus rods) and honeybees (ultraviolet,... (Review)
Review
Butterflies use colour vision when searching for flowers. Unlike the trichromatic retinas of humans (blue, green and red cones; plus rods) and honeybees (ultraviolet, blue and green photoreceptors), butterfly retinas typically have six or more photoreceptor classes with distinct spectral sensitivities. The eyes of the Japanese yellow swallowtail (Papilio xuthus) contain ultraviolet, violet, blue, green, red and broad-band receptors, with each ommatidium housing nine photoreceptor cells in one of three fixed combinations. The Papilio eye is thus a random patchwork of three types of spectrally heterogeneous ommatidia. To determine whether Papilio use all of their receptors to see colours, we measured their ability to discriminate monochromatic lights of slightly different wavelengths. We found that Papilio can detect differences as small as 1-2 nm in three wavelength regions, rivalling human performance. We then used mathematical modelling to infer which photoreceptors are involved in wavelength discrimination. Our simulation indicated that the Papilio vision is tetrachromatic, employing the ultraviolet, blue, green and red receptors. The random array of three ommatidial types is a common feature in butterflies. To address the question of how the spectrally complex eyes of butterflies evolved, we studied their developmental process. We have found that the development of butterfly eyes shares its molecular logic with that of Drosophila: the three-way stochastic expression pattern of the transcription factor Spineless determines the fate of ommatidia, creating the random array in Papilio.
Topics: Animals; Butterflies; Color Vision; Photoreceptor Cells, Invertebrate; Retina
PubMed: 28332207
DOI: 10.1113/JP273917 -
Experimental Eye Research Nov 2021Adult zebrafish are capable of functional retinal regeneration following damage. A goal of vision science is to stimulate or permit a similar process in mammals to treat... (Review)
Review
Adult zebrafish are capable of functional retinal regeneration following damage. A goal of vision science is to stimulate or permit a similar process in mammals to treat human retinal disease and trauma. Ideally such a process would reconstitute the stereotyped, two-dimensional topographic patterns and regional specializations of specific cell types, functionally important for representation of the visual field. An example in humans is the cone-rich fovea, essential for high-acuity color vision. Stereotyped, global topographic patterns of specific retinal cell types are also found in zebrafish, particularly for cone types expressing the tandemly-replicated lws (long wavelength-sensitive) and rh2 (middle wavelength-sensitive) opsins. Here we examine whether regionally specialized patterns of LWS1 and LWS2 cones are restored in regenerated retinas in zebrafish. Adult transgenic zebrafish carrying fluorescent reporters for lws1 and lws2 were subjected to retinal lesions that destroy all neurons but spare glia, via intraocular injection of the neurotoxin ouabain. Regenerated and contralateral control retinas were mounted whole or sectioned, and imaged. Overall spatial patterns of lws1 vs. lws2 opsin-expressing cones in regenerated retinas were remarkably similar to those of control retinas, with LWS1 cones in ventral/peripheral regions, and LWS2 cones in dorsal/central regions. However, LWS2 cones occupied a smaller fraction of regenerated retina, and several cones co-expressed the lws1 and lws2 reporters in regenerated retinas. Local patterns of regenerated LWS1 cones showed modest reductions in regularity. These results suggest that some of the regional patterning information, or the source of such signals, for LWS cone subtypes may be retained by undamaged cell types (Müller glia or RPE) and re-deployed during regeneration.
Topics: Animals; Animals, Genetically Modified; Models, Animal; Regeneration; Retina; Zebrafish
PubMed: 34653519
DOI: 10.1016/j.exer.2021.108789 -
IEEE Transactions on Ultrasonics,... Dec 2022Ultrasound neuromodulation is an emerging technology. A significant amount of effort has been devoted to investigating the feasibility of noninvasive ultrasound retinal... (Review)
Review
Ultrasound neuromodulation is an emerging technology. A significant amount of effort has been devoted to investigating the feasibility of noninvasive ultrasound retinal stimulation. Recent studies have shown that ultrasound can activate neurons in healthy and degenerated retinas. Specifically, high-frequency ultrasound can evoke localized neuron responses and generate patterns in visual circuits. In this review, we recapitulate pilot studies on ultrasound retinal stimulation, compare it with other neuromodulation technologies, and discuss its advantages and limitations. An overview of the opportunities and challenges to develop a noninvasive retinal prosthesis using high-frequency ultrasound is also provided.
Topics: Retina; Visual Prosthesis; Ultrasonography
PubMed: 36343006
DOI: 10.1109/TUFFC.2022.3220568 -
The International Journal of... 2004The optic vesicle gives rise to several very different epithelial tissues, including the neural retina, the pigmented epithelium, the iris, the ciliary epithelium of the... (Review)
Review
The optic vesicle gives rise to several very different epithelial tissues, including the neural retina, the pigmented epithelium, the iris, the ciliary epithelium of the ciliary body and the optic stalk. Retinal regeneration can arise from several different cellular sources; in some species, the process involves interconversion, or transdifferentiation, among cells of the different tissue types. Therefore, prior to a discussion of retinal regeneration, we will briefly discuss current knowledge about the influence of signaling molecules in cell fate determination in ocular tissues. Next, we will detail the evidence for neurogenesis in the mature retina. Lastly, we will describe various types of regenerative phenomena that occur in the retina, from complete regeneration of functional retina in fish and amphibians, to the more limited neuronal production that occurs in avian and mammalian retinas.
Topics: Animals; Cell Differentiation; Cell Lineage; Chick Embryo; Ciliary Body; Eye; Humans; Models, Anatomic; Models, Biological; Pigment Epithelium of Eye; Regeneration; Retina; Salamandridae; Signal Transduction; Stem Cells
PubMed: 15558491
DOI: 10.1387/ijdb.041870am