Novel distribution of junctional adhesion molecule‐C in the neural retina and retinal pigment epithelium

Daniele, Lauren L.; Adams, Ralf H.; Durante, Diane E.; Pugh, Edward N.; Philp, Nancy J.

doi:10.1002/cne.21489

Cited by 50 publications

(46 citation statements)

References 60 publications

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“…The viral myocarditis pathway (hsa05416) contains CAV1 (Caveolin 1) previously shown to be associated with POAG (Thorleifsson et al 2010; Wiggs et al 2011). In the cell adhesion pathway, JAM2 is a component of the neural retina and retinal pigment epithelium (Daniele et al 2007) and PVRL3 has previously been shown to contribute to ocular developmental defects (Lachke et al 2012). …”

Section: Resultsmentioning

confidence: 99%

Hypothesis-independent pathway analysis implicates GABA and Acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma

et al. 2014

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Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Using genome-wide association single-nucleotide polymorphism data from the Glaucoma Genes and Environment study and National Eye Institute Glaucoma Human Genetics Collaboration comprising 3,108 cases and 3,430 controls, we assessed biologic pathways as annotated in the KEGG database for association with risk of POAG. After correction for genic overlap among pathways, we found 4 pathways, butanoate metabolism (hsa00650), hematopoietic cell lineage (hsa04640), lysine degradation (hsa00310) and basal transcription factors (hsa03022) related to POAG with permuted p < 0.001. In addition, the human leukocyte antigen (HLA) gene family was significantly associated with POAG (p < 0.001). In the POAG subset with normal-pressure glaucoma (NPG), the butanoate metabolism pathway was also significantly associated (p < 0.001) as well as the MAPK and Hedgehog signaling pathways (hsa04010 and hsa04340), glycosaminoglycan biosynthesis-heparan sulfate pathway (hsa00534) and the phenylalanine, tyrosine and tryptophan biosynthesis pathway (hsa0400). The butanoate metabolism pathway overall, and specifically the aspects of the pathway that contribute to GABA and acetyl-CoA metabolism, was the only pathway significantly associated with both POAG and NPG. Collectively these results implicate GABA and acetyl-CoA metabolism in glaucoma pathogenesis, and suggest new potential therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Hypothesis-independent pathway analysis implicates GABA and Acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma

et al. 2014

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“…A number of PM proteins that are sorted basolaterally in most epithelia have an apical or non-polar distribution in RPE cells. These include the Transferrin Receptor (TfR) (Perez Bay et al, 2013), the Coxsackie-Adenovirus Receptor (CAR) (Diaz et al, 2009), JAM C (Daniele et al, 2007) and the Neural Cell Adhesion Molecule (NCAM)(Gundersen et al, 1993). The apical localization of CAR and TfR results from the transcytosis of these receptors to the apical PM from common recycling endosomes (CRE) (Diaz et al, 2009; Perez Bay et al, 2013).…”

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

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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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“…Frozen sections of paraformaldehyde-fixed mouse eyes were prepared for immunohistochemical analysis and confocal imaging as previously described (11 Ϫ/Ϫ mice, and RPE-choroid and retinal lysates were prepared for immunoblot analysis as previously described (11,34).…”

Section: Animalsmentioning

confidence: 99%

Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice

Daniele¹,

Sauer²,

Gallagher³

et al. 2008

American Journal of Physiology-Cell Physiology

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To meet the high-energy demands of photoreceptor cells, the outer retina metabolizes glucose through glycolytic and oxidative pathways, resulting in large-scale production of lactate and CO2. Mct3, a protoncoupled monocarboxylate transporter, is critically positioned to facilitate transport of lactate and H ϩ out of the retina and could therefore play a role in pH and ion homeostasis of the outer retina. Mct3 is preferentially expressed in the basolateral membrane of the retinal pigment epithelium and forms a heteromeric complex with the accessory protein CD147. To examine the physiological role of Mct3 in the retina, we generated mice with a targeted deletion in Mct3 (slc16A8). The overall retinal histology of 4-to 36-wk-old Mct3Ϫ/Ϫ mice appeared normal. In the absence of Mct3, expression of CD147 was lost from the basolateral but not apical RPE. The saturated a-wave amplitude (amax) of the scotopic electroretinogram (ERG) was reduced by approximately twofold in Mct3 Ϫ/Ϫ mice relative to wildtype mice. A fourfold increase in lactate in the retina suggested a decrease in outer-retinal pH. In single-cell recordings from superfused retinal slices, saturating amplitudes of single rod photocurrents (Jmax) were comparable indicating that Mct3 Ϫ/Ϫ mouse photoreceptor cells were inherently healthy. Based on these data, we hypothesize that disruption of Mct3 leads to a potentially reversible decrease in subretinal space pH, thereby reducing the magnitude of the light suppressible photoreceptor current. monocarboxylate transporter 3; lactate transport; retinal pigment epithleium; pH regulation; photoreceptor; electroretinogram THE RETINAL PIGMENT EPITHELIUM (RPE) forms the outer-blood retinal barrier and performs many functions essential for maintaining the health and functional activity of photoreceptors. Interposed between the choroidal vessels and the photoreceptor cells, the RPE regulates the transport of glucose to the avascular outer retina. Eighty percent of the glucose transported into the outer retina is metabolized via glycolysis producing large amounts of lactate both in the light and the dark (41,42,44). Lactate produced by glycolysis in Müller glia is then used to fuel oxidative phosphorylation in photoreceptor cells (35). The transfer of lactate from glia to neurons is facilitated by proton-coupled monocarboxylate transporters and has been referred to as the "lactate shuttle" (27). Inhibition of monocarboxylate transport or glycolysis results in attenuation of light-

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Novel distribution of junctional adhesion molecule‐C in the neural retina and retinal pigment epithelium

Cited by 50 publications

References 60 publications

Hypothesis-independent pathway analysis implicates GABA and Acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma

Hypothesis-independent pathway analysis implicates GABA and Acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma

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

Altered visual function in monocarboxylate transporter 3 (Slc16a8) knockout mice

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