The outer limiting membrane (OLM) revisited: clinical implications

Behar‐Cohen, Francine

doi:10.2147/opth.s5901

Cited by 93 publications

(37 citation statements)

References 21 publications

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“…In the retina, labeling was detected in the outer limiting membrane (OLM) (arrowhead in Fig. 2F ), which has been previously shown to contain both AJ and TJ proteins [20] , and along the junctions between retinal pigmented epithelial cells (arrow in Fig. 2F ).…”

Section: Resultsmentioning

confidence: 90%

PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherin

et al. 2010

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The pleckstrin-homology-domain-containing protein PLEKHA7 was recently identified as a protein linking the E-cadherin-p120 ctn complex to the microtubule cytoskeleton. Here we characterize the expression, tissue distribution and subcellular localization of PLEKHA7 by immunoblotting, immunofluorescence microscopy, immunoelectron microscopy, and northern blotting in mammalian tissues. Anti-PLEKHA7 antibodies label the junctional regions of cultured kidney epithelial cells by immunofluorescence microscopy, and major polypeptides of Mr ∼135 kDa and ∼145 kDa by immunoblotting of lysates of cells and tissues. Two PLEKHA7 transcripts (∼5.5 kb and ∼6.5 kb) are detected in epithelial tissues. PLEKHA7 is detected at epithelial junctions in sections of kidney, liver, pancreas, intestine, retina, and cornea, and its tissue distribution and subcellular localization are distinct from ZO-1. For example, PLEKHA7 is not detected within kidney glomeruli. Similarly to E-cadherin, p120 ctn, β-catenin and α-catenin, PLEKHA7 is concentrated in the apical junctional belt, but unlike these adherens junction markers, and similarly to afadin, PLEKHA7 is not localized along the lateral region of polarized epithelial cells. Immunoelectron microscopy definitively establishes that PLEKHA7 is localized at the adherens junctions in colonic epithelial cells, at a mean distance of 28 nm from the plasma membrane. In summary, we show that PLEKHA7 is a cytoplasmic component of the epithelial adherens junction belt, with a subcellular localization and tissue distribution that is distinct from that of ZO-1 and most AJ proteins, and we provide the first description of its distribution and localization in several tissues.

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Section: Resultsmentioning

confidence: 90%

PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherin

et al. 2010

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“…Herein we address the implication of the overlooked outer barriers in diabetic retinopathy in a rat model of type2 diabetes. We have recently shown that the OLM is not only formed by adherent junctions between glial Müller cells and photoreceptors but also contains heterotypic tight-junctions, suggesting that the OLM should be considered as part of the outer retinal barrier [6] . However, what regulates this barrier and what are the consequences of OLM barrier function alteration in the course of diabetes has not been explored.…”

Section: Discussionmentioning

confidence: 99%

“…The apical side of RPE faces the photoreceptor outer segments of the neuroretina, and the basolateral side lies on Bruch's membrane, which separates the RPE from the underlying fenestrated endothelium of the choriocapillaris [5] . We have recently evidenced that tight-like junctions containing occludin are present also at the OLM, mainly between Müller glial cells and cones, the only photoreceptors of the macula [6] . Among the molecules involved in TJ formation and maintenance, the critical role of the PAR6/PKCζ/PAR3 scaffold complex in cell polarity has been extensively studied [7] – [13] .…”

Section: Introductionmentioning

confidence: 99%

PKCζ Mediates Breakdown of Outer Blood-Retinal Barriers in Diabetic Retinopathy

et al. 2013

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Aims/hypothesisDiabetic macular edema represents the main cause of visual loss in diabetic retinopathy. Besides inner blood retinal barrier breakdown, the role of the outer blood retinal barrier breakdown has been poorly analyzed. We characterized the structural and molecular alterations of the outer blood retinal barrier during the time course of diabetes, focusing on PKCζ, a critical protein for tight junction assembly, known to be overactivated by hyperglycemia.MethodsStudies were conducted on a type2 diabetes Goto-Kakizaki rat model. PKCζ level and subcellular localization were assessed by immunoblotting and immunohistochemistry. Cell death was detected by TUNEL assays. PKCζ level on specific layers was assessed by laser microdissection followed by Western blotting. The functional role of PKCζ was then evaluated in vivo, using intraocular administration of its specific inhibitor.ResultsPKCζ was localized in tight junction protein complexes of the retinal pigment epithelium and in photoreceptors inner segments. Strikingly, in outer segment PKCζ staining was restricted to cone photoreceptors. Short-term hyperglycemia induced activation and delocalization of PKCζ from both retinal pigment epithelium junctions and cone outer segment. Outer blood retinal barrier disruption and photoreceptor cone degeneration characterized long-term hyperglycemia. In vivo, reduction of PKCζ overactivation using a specific inhibitor, restored its tight-junction localization and not only improved the outer blood retinal barrier, but also reduced photoreceptor cell-death.ConclusionsIn the retina, hyperglycemia induced overactivation of PKCζ is associated with outer blood retinal barrier breakdown and photoreceptor degeneration. In vivo, short-term inhibition of PKCζ restores the outer barrier structure and reduces photoreceptor cell death, identifying PKCζ as a potential target for early and underestimated diabetes-induced retinal pathology.

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“…Muller glia form adherens junctions with PR demarking the junction between outer nuclear and IS layers (Bunt-Milam et al, 1985;Williams et al, 1990). These junctions and the band of actin filaments running between them form a readily visible line in histological preparations of the retina and historically were given the misnomer of the outer limiting membrane (Williams et al, 1990;Omri et al, 2010). Muller glia extend microvilli past this junctional belt.…”

Section: Retinamentioning

confidence: 99%

A Comparison of the Primary Sensory Neurons Used in Olfaction and Vision

Lankford

Laird

Inamdar

et al. 2020

Front. Cell. Neurosci.

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Vision, hearing, smell, taste, and touch are the tools used to perceive and navigate the world. They enable us to obtain essential resources such as food and highly desired resources such as mates. Thanks to the investments in biomedical research the molecular unpinning's of human sensation are rivaled only by our knowledge of sensation in the laboratory mouse. Humans rely heavily on vision whereas mice use smell as their dominant sense. Both modalities have many features in common, starting with signal detection by highly specialized primary sensory neurons-rod and cone photoreceptors (PR) for vision, and olfactory sensory neurons (OSN) for the smell. In this chapter, we provide an overview of how these two types of primary sensory neurons operate while highlighting the similarities and distinctions.

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The outer limiting membrane (OLM) revisited: clinical implications

Cited by 93 publications

References 21 publications

PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherin

PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherin

PKCζ Mediates Breakdown of Outer Blood-Retinal Barriers in Diabetic Retinopathy

A Comparison of the Primary Sensory Neurons Used in Olfaction and Vision

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