Origin and organization of pigment epithelial apical projections to cones in cat retina

Fisher, Steven K.; Steinberg, Roy H.

doi:10.1002/cne.902060204

Cited by 36 publications

(24 citation statements)

References 23 publications

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“…C57BL/6J mice were housed at University of California, Los Angeles and used at age 6 wk. Adult cat, Felis catus, and rhesus monkey, Macaca mulatta, tissues were from previous studies performed at University of California, Santa Barbara, and University of California, San Francisco (43,44). All animals were kept on a 12-h light/12-h dark cycle, and treated in accordance with appropriate institutional guidelines.…”

Section: Methodsmentioning

confidence: 99%

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Three-dimensional organization of nascent rod outer segment disk membranes

Volland

Hughes

Kong

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The vertebrate photoreceptor cell contains an elaborate cilium that includes a stack of phototransductive membrane disks. The disk membranes are continually renewed, but how new disks are formed remains poorly understood. Here we used electron microscope tomography to obtain 3D visualization of the nascent disks of rod photoreceptors in three mammalian species, to gain insight into the process of disk morphogenesis. We observed that nascent disks are invariably continuous with the ciliary plasma membrane, although, owing to partial enclosure, they can appear to be internal in 2D profiles. Tomographic analyses of the basal-most region of the outer segment show changes in shape of the ciliary plasma membrane indicating an invagination, which is likely a first step in disk formation. The invagination flattens to create the proximal surface of an evaginating lamella, as well as membrane protrusions that extend between adjacent lamellae, thereby initiating a disk rim. Immediately distal to this initiation site, lamellae of increasing diameter are evident, indicating growth outward from the cilium. In agreement with a previous model, our data indicate that mature disks are formed once lamellae reach full diameter, and the growth of a rim encloses the space between adjacent surfaces of two lamellae. This study provides 3D data of nascent and mature rod photoreceptor disk membranes at unprecedented z-axis depth and resolution, and provides a basis for addressing fundamental questions, ranging from protein sorting in the photoreceptor cilium to photoreceptor electrophysiology.photoreceptor | cilium | EM tomography | disk morphogenesis P rimary cilia detect extracellular signals via membrane receptors or channels. The most elaborate of all cilia, the cilium that forms the vertebrate photoreceptor outer segment (OS), includes a large stack of membrane disks that extends distally from the transition zone, also known as the connecting cilium (1). The OS disks contain the visual receptor, opsin, and their tight packing allows for a high concentration of opsin within a confined space, thereby limiting the trade-off between visual sensitivity and spatial resolution. Turnover of OS disk membranes occurs throughout the lifetime of an animal (2) and requires the de novo synthesis and degradation of large amounts of OS proteins; on average, 9-10 billion opsin molecules are turned over every second in each human retina (3).A key event in OS disk turnover is the formation of disk membranes from newly synthesized molecules that are trafficked as vesicles from the endoplasmic reticulum (ER)/Golgi in the inner segment to the cilium (4, 5). Disk membrane morphogenesis is essential for the survival of photoreceptor cells. Orthologs of gene mutations that disrupt disk formation in mice have been linked to various retinal degenerations in humans; for example, in the rds mouse [mutant in peripherin-2 (Prph2)], disks do not develop from the end of the connecting cilium (6, 7), and in mice whose photoreceptors express mutant human prominin-1 (...

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Section: Methodsmentioning

confidence: 99%

“…Samples were then washed in acetone and propylene oxide, and embedded in Araldite 502. Cat and monkey tissue was fixed using transcardiac perfusion, as described previously (43,44).…”

Section: Methodsmentioning

confidence: 99%

Three-dimensional organization of nascent rod outer segment disk membranes

Volland

Hughes

Kong

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Hedgehog) and the transduction of environmental stimuli (mechano, chemo, and osmosensory functions) (Gerdes, 2009; Goetz, 2010). Early studies reported that adult RPE display a PC that is spatially correlated with the presence of cones in the neural retina (Fisher and Steinberg, 1982). More recent immunofluorescence analysis on mouse RPE flatmounts using antibodies against acetylated tubulin concluded that RPE PC is present in developing RPE but disappears in the mature retina (Nishiyama et al, 2002).…”

Section: Structural and Functional Polarity Of Rpe Cellsmentioning

confidence: 99%

Plasma membrane protein polarity and trafficking in RPE cells: Past, present and future

Lehmann

Benedicto

Philp

et al. 2014

Experimental Eye Research

104

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The retinal pigment epithelium (RPE) comprises a monolayer of polarized pigmented epithelial cells that is strategically interposed between the neural retina and the fenestrated choroid capillaries. The RPE performs a variety of vectorial transport functions (water, ions, metabolites, nutrients and waste products) that regulate the composition of the subretinal space and support the functions of photoreceptors (PRs) and other cells in the neural retina. To this end, RPE cells display a polarized distribution of channels, transporters and receptors in their plasma membrane (PM) that is remarkably different from that found in conventional extra-ocular epithelia, e.g. intestine, kidney, and gall bladder. This characteristic PM protein polarity of RPE cells depends on the interplay of sorting signals in the RPE PM proteins and sorting mechanisms and biosynthetic/recycling trafficking routes in the RPE cell. Although considerable progress has been made in our understanding of the RPE trafficking machinery, most available data have been obtained from immortalized RPE cell lines that only partially maintain the RPE phenotype and by extrapolation of data obtained in the prototype Madin–Darby Canine Kidney (MDCK) cell line. The increasing availability of RPE cell cultures that more closely resemble the RPE in vivo together with the advent of advanced live imaging microscopy techniques provides a platform and an opportunity to rapidly expand our understanding of how polarized protein trafficking contributes to RPE PM polarity.

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“…The relationship with cone photoreceptors was confirmed by electron microscopy (not illustrated) in which the EAAT4-positive projections were seen to fill the supracone space and surround individual cone outer segments. Such structures have been described previously in the cat retina by Fisher and Steinberg (1982) and termed cone sheaths. Dense staining for EAAT4 was also seen in fibrous processes near the inner limiting membrane (Fig.…”

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confidence: 94%

Differential cellular and subcellular distribution of glutamate transporters in the cat retina

et al. 2004

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Retrieval of glutamate from extracellular sites in the retina involves at least five excitatory amino acid transporters. Immunocytochemical analysis of the cat retina indicates that each of these transporters exhibits a selective distribution which may reflect its specific function. The uptake of glutamate into Muller cells or astrocytes appears to depend upon GLAST and EAAT4, respectively. Staining for EAAT4 was also seen in the pigment epithelium. The remaining transporters are neuronal with GLT-1alpha localized to a number of cone bipolar, amacrine, and ganglion cells and GLT-1v in cone photoreceptors and several populations of bipolar cells. The EAAC1 transporter was found in horizontal, amacrine, and ganglion cells. Staining for EAAT5 was seen in the axon terminals of both rod and cone photoreceptors as well as in numerous amacrine and ganglion cells. Although some of the glutamate transporter molecules are positioned for presynaptic or postsynaptic uptake at glutamatergic synapses, others with localizations more distant from such contacts may serve in modulatory roles or provide protection against excitoxic or oxidative damage.

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Origin and organization of pigment epithelial apical projections to cones in cat retina

Cited by 36 publications

References 23 publications

Three-dimensional organization of nascent rod outer segment disk membranes

Three-dimensional organization of nascent rod outer segment disk membranes

Plasma membrane protein polarity and trafficking in RPE cells: Past, present and future

Differential cellular and subcellular distribution of glutamate transporters in the cat retina

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