Macromolecular cell markers are essential for the classification and characterization of the highly complex and cellularly diverse vertebrate retina. Although a plethora of markers are described in the current literature, the immunoreactivity of these markers in normal human tissue has not been fully determined. This is problematic as they are quintessential to the characterization of morphological changes associated with human retinal disease. This review provides an overview of the macromolecular markers currently available to assess human retinal cell types. We draw on immunohistochemical studies conducted in our laboratories to describe marker immunoreactivity in human retina alongside comparative descriptions in non-human tissues. Considering the growing number of eye banks services offering healthy and diseased human retinal tissue, this review provides a point of reference for future human retina studies and highlights key species specific disease applications of some macromolecular markers.
Gap junctions are specialized cell-to-cell contacts that allow the direct transfer of small molecules between cells. A single gap junction channel consists of two hemichannels, or connexons, each of which is composed of six connexin protein subunits. Connexin43 is the most ubiquitously expressed isoform of the connexin family and in the retina it is prevalent in astrocytes, Muller cells, microglia, retinal pigment epithelium and endothelial cells. Prior to docking with a neighboring cell, Connex...
Last. Ulrike Grünert(USYD: University of Sydney)H-Index: 49
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Antibodies against calretinin are markers for one type of rod pathway interneuron (AⅡ amacrine cell) in the retina of some but not all mammalian species. The AⅡ cells play a crucial role in night-time (scotopic) vision and have been proposed as a target for optogenetic restoration of vision in retinal disease. In the present study we aimed to characterize the AⅡ cells in human retina. Postmortem human donor eyes were obtained with ethical approval and processed for calretinin immunofluorescence....
While photoreceptor loss is the most devastating result of inherited retinal degenerations such as retinitis pigmentosa, inner retinal neurons also undergo significant alteration. Detailing these changes has become important as many vision restorative therapies target the remaining neurons. In this study, the rd1-Fos-Tau-LacZ (rd1-FTL) mouse model was used to explore inner retinal change at a late stage of retinal degeneration, after the loss of photoreceptor nuclei. The rd1-FTL model carries a ...
Purpose To evaluate the histopathology in donor eyes from patients with autosomal dominant retinitis pigmentosa (ADRP) caused by p.P23H, p.P347T and p.P347L rhodopsin ( RHO ) gene mutations.
Abstract Retinal neurodegenerative diseases like age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa each have a different etiology and pathogenesis. However, at the cellular and molecular level, the response to retinal injury is similar in all of them, and results in morphological and functional impairment of retinal cells. This retinal degeneration may be triggered by gene defects, increased intraocular pressure, high levels of blood glucose, other types o...
Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide in the elderly population. Optometrists, as primary eye health care providers, require the skills and knowledge to accurately diagnose and manage AMD patients. There is an overwhelming body of research related to the clinical presentation, etiology, epidemiology, and pathology of this disease. Additionally, the evolution of new imaging modalities creates new opportunities to clinically detect and analyze p...
Last. Samer Hattar(Johns Hopkins University)H-Index: 37
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Alterations in normal patterns of exposure to light disrupt circadian rhythms and sleep, and have a profound effect on health and mood. Hattar and colleagues describe the role of intrinsically photosensitive retinal ganglion cells in mediating the direct and indirect effects of light on mood and cognition.
This study characterizes the developmental patterns of seven key amino acids: glutamate, γ-amino-butyric acid (GABA), glycine, glutamine, aspartate, alanine and taurine in the mouse retina. We analyze amino acids in specific bipolar, amacrine and ganglion cell sub-populations (i.e. GABAergic vs. glycinergic amacrine cells) and anatomically distinct regions of photoreceptors and Muller cells (i.e. cell bodies vs. endfeet) by extracting data from previously described pattern recognition analysis. ...
Abstract Vinpocetine is a natural drug which exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. This study investigated the effect of vinpocetine on cation channel permeability of inner retinal neurons after acute retinal metabolic insult. We focused on amacrine and ganglion cells immunoreactive for calretinin or parvalbumin due to their previously documented susceptibility to ischaemia. Using the probe, 1-amino-4-...
Pattern recognition has been used for the complete and statistically rigid classification of retinal neurons in vertebrates such as the adult cat, primate, rat and goldfish. Here, we label the mouse retina with antibodies against seven amino acids and use pattern recognition to characterize distinct retinal neurochemical cell classes based on their unique amino acid signatures. We followed the development of the cell classes in the X-inactivation transgenic mouse expressing the lacZ reporter gen...
Last. Ulrike Grünert(USYD: University of Sydney)H-Index: 49
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Purpose The purpose of this study was to measure the composition of the inner nuclear layer (INL) in the central and peripheral human retina as foundation data for interpreting INL function and dysfunction. Methods Six postmortem human donor retinas (male and female, aged 31-56 years) were sectioned along the temporal horizontal meridian. Sections were processed with immunofluorescent markers and imaged using high-resolution, multichannel fluorescence microscopy. The density of horizontal, bipol...
Last. Maria Ana Contin(National University of Cordoba)H-Index: 12
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Retinal damage promoted by constant illumination of low intensity resulted in a diminution in classical photoreceptors cells. Glial cells exert profound effects on neurons, vasculature and other glial cells. Macroglia and microglia with specific morphological, physiological, and antigenic characteristics may play an essential role in both the maintenance and control of retinal homeostasis, or to exert mechanisms that promote cell death. The role of glial cells and immune function in the pathogen...
#2Rogier M. Vos(KNAW: Royal Netherlands Academy of Arts and Sciences)H-Index: 10
Last. Jan Wijnholds(KNAW: Royal Netherlands Academy of Arts and Sciences)H-Index: 46
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Abstract Loss of CRB1 or CRB2 proteins in Muller cells or photoreceptors in the mouse retina results in a CRB-dose-dependent retinal phenotype. Here, we present a novel Muller cell-specific Crb1KOCrb2LowMGC retinitis pigmentosa mouse model (Complete loss of CRB1 and reduced levels of CRB2 specifically in Muller cells). The Crb double mutant mice showed deficits in electroretinography, optokinetic head tracking, and retinal morphology. Exposure of retinas to low levels of DL-α-aminoadipate acid i...
Introduction: Research in to the pathophysiology of the complex layers of retinal and sub-retinal cells is hampered by inadequate recognition of particular cells and tissues. A comprehensive panel ...
Last. Paul R. Martin(USYD: University of Sydney)H-Index: 52
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Two main subcortical pathways serving conscious visual perception are the midget-parvocellular (P), and the parasol-magnocellular (M) pathways. It is generally accepted that the P pathway serves red-green color vision, but the relative contribution of P and M pathways to spatial vision is a long-standing and unresolved issue. Here, we mapped the spatial sampling properties of P and M pathways across the human retina. Data were obtained from immunolabeled vertical sections of six postmortem male ...
Last. Jingming Li(Xi'an Jiaotong University)H-Index: 3
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Aim To investigate whether inhibition of acetylcholinesterase (AChE) by donepezil ameliorate aberrant retinal neovascularization (RNV) and abnormal glial activation in oxygen-induced retinopathy (OIR). Methods A mouse model of RNV was induced in postnatal day 7 (P7) mice by exposure to 75% oxygen. Donepezil was administrated to P12 mice by intraperitoneal injection. Expression and localization of AChE in mouse retinas were determined by immunofluorescence. RNV was evaluated by paraffin sectionin...
Last. Ulrike Grünert(USYD: University of Sydney)H-Index: 49
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: In primate retina, the calcium-binding protein calbindin is expressed by a variety of neurons including cones, bipolar cells, and amacrine cells but it is not known which type(s) of cell express calbindin in the ganglion cell layer. The present study aimed to identify calbindin-positive cell type(s) in the amacrine and ganglion cell layer of human and marmoset retina using immunohistochemical markers for ganglion cells (RBPMS and melanopsin) and cholinergic amacrine (ChAT) cells. Intracellular...
ABSTRACTThis review presents the extent to which engagement in research and new developments in clinical practice alike have contributed to the establishment and development of the primary vision care profession in New Zealand that is Optometry. Many notable changes have occurred in the scope of practice of the profession over the past three decades and an important role of visual neuroscience, neurobiology and pharmaceuticals allowed the introduction of therapeutic prescribing responsibilities ...
Last. Wyeth W. Wasserman(UBC: University of British Columbia)H-Index: 61
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Retinal gene therapy is leading the neurological gene therapy field, with 32 ongoing clinical trials of recombinant adeno-associated virus (rAAV)-based therapies. Importantly, over 50% of those trials are using restricted promoters from human genes. Promoters that restrict expression have demonstrated increased efficacy, and can limit the therapeutic to the target cells thereby reducing unwanted off-target effects. Retinal ganglion cells are a critical target in ocular gene therapy; they are inv...
Last. Ulrike Grünert(USYD: University of Sydney)H-Index: 49
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Purpose: Particle-mediated gene transfer has been used in animal models to study the morphology and connectivity of retinal ganglion cells. The aim of the present study was to apply this method to transfect ganglion cells in postmortem human retina. Methods: Postmortem human eyes from male and female donors aged 40 to 76 years old were obtained within 15 hours after death. In addition, two marmoset retinas were obtained immediately after death. Ganglion cells were transfected with an expression ...
