Controlled exosome release from the retinal pigment epithelium in situ

Locke, Christina; Congrove, Nicole R.; Dismuke, W. Michael; Bowen, Trent J; Stamer, W. Daniel; McKay, Brian S.

doi:10.1016/j.exer.2014.10.010

Cited by 43 publications

(45 citation statements)

References 18 publications

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“…The size distribution of EVs released apically from human eyecups (posterior half with vitreous and neuroretina removed and RPE exposed) ex vivo has recently been described 32 . Thus we analyzed EVs isolated from pig eyecups and EVs from our in vitro cultures to compare the size distribution of ex vivo pig RPE-derived EVs with our in vitro RPE-derived EVs (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Although the RPE has vastly different functions at its apical and basal surfaces in vivo , which is also reflected in the EVs secreted in either direction; only apically released EVs can be obtained from ex vivo eyecups 32 . In contrast, the in vitro RPE model we have presented here can be used to study both apical and basolateral vesicle release and to test how disease-associated stressors affect it.…”

Section: Discussionmentioning

confidence: 99%

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Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers

Klingeborn

Dismuke

Skiba

et al. 2017

Sci Rep

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102

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The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier in the eye and its polarity is responsible for directional secretion and uptake of proteins, lipoprotein particles and extracellular vesicles (EVs). Such a secretional division dictates directed interactions between the systemic circulation (basolateral) and the retina (apical). Our goal is to define the polarized proteomes and physical characteristics of EVs released from the RPE. Primary cultures of porcine RPE cells were differentiated into polarized RPE monolayers on permeable supports. EVs were isolated from media bathing either apical or basolateral RPE surfaces, and two subpopulations of small EVs including exosomes, and dense EVs, were purified and processed for proteomic profiling. In parallel, EV size distribution and concentration were determined. Using protein correlation profiling mass spectrometry, a total of 631 proteins were identified in exosome preparations, 299 of which were uniquely released apically, and 94 uniquely released basolaterally. Selected proteins were validated by Western blot. The proteomes of these exosome and dense EVs preparations suggest that epithelial polarity impacts directional release. These data serve as a foundation for comparative studies aimed at elucidating the role of exosomes in the molecular pathophysiology of retinal diseases and help identify potential therapeutic targets and biomarkers.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers

Klingeborn

Dismuke

Skiba

et al. 2017

Sci Rep

Self Cite

102

View full text Add to dashboard Cite

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“…4). In other studies, myocilin was released from the RPE in situ associated with exosomes and this release was under the control of a G-protein-coupled receptor (Locke et al, 2014). Finally, proteomic analysis of exosomes released from primary cultures of human TM cell monolayers contained an abundance of myocilin (Stamer et al, 2011).…”

Section: Exosomes and Extracellular Matrix (Ecm)mentioning

confidence: 96%

Roles of exosomes in the normal and diseased eye

Klingeborn

Dismuke

Rickman

et al. 2017

Progress in Retinal and Eye Research

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139

127

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Exosomes are nanometer-sized vesicles that are released by cells in a controlled fashion and mediate a plethora of extra- and intercellular activities. Some key functions of exosomes include cell-cell communication, immune modulation, extracellular matrix turnover, stem cell division/differentiation, neovascularization and cellular waste removal. While much is known about their role in cancer, exosome function in the many specialized tissues of the eye is just beginning to undergo rigorous study. Here we review current knowledge of exosome function in the visual system in the context of larger bodies of data from other fields, in both health and disease. Additionally, we discuss recent advances in the exosome field including use of exosomes as a therapeutic vehicle, exosomes as a source of biomarkers for disease, plus current standards for isolation and validation of exosome populations. Finally, we use this foundational information about exosomes in the eye as a platform to identify areas of opportunity for future research studies.

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“…Exosomes are thought to function in inter‐tissue communication as they carry mRNA, miRNA, proteins, and bioactive lipids. RPE are known to release both apical and basal exosomes (Biasutto, Chiechi, Couch, Liotta, & Espina, ; Kannan, Sreekumar, & Hinton, ; Locke et al, ; Sreekumar et al, ; Wang et al, , ). Apical exosomes have the capacity to function as carriers from the RPE to the retina.…”

Section: Gpr143mentioning

confidence: 99%

“…GPR143 signaling in RPE also controls of release of apical exosomes (Locke et al, 2014). Exosomes are small extracellular vesicles, 40-150 nM in diameter, produced and accumulated in the multivesicular body (MVB), for review (Pant, Hilton, & Burczynski, 2012).…”

Section: Gp R 14mentioning

confidence: 99%

Pigmentation and vision: Is GPR143 in control?

McKay

2018

J of Neuroscience Research

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Albinism, typically characterized by decreased melanin synthesis, is associated with significant visual deficits owing to developmental changes during neurosensory retina development. All albinism is caused by genetic mutations in a group of diverse genes including enzymes, transporters, G-protein coupled receptor. Interestingly, these genes are not expressed in the neurosensory retina. Further, regardless of cause of albinism, all forms of albinism have the same retinal pathology, the extent of which is variable. In this review, we explore the possibility that this similarity in retinal phenotype is because all forms of albinism funnel through the same final common pathway. There are currently seven known genes linked to the seven forms of ocular cutaneous albinism. These types of albinism are the most common, and result in changes to all pigmented tissues (hair, skin, eyes). We will discuss the incidence and mechanism, where known, to develop a picture as to how the mutations cause albinism. Next, we will examine the one form of albinism which causes tissue-specific pathology, ocular albinism, where the eye exhibits the retinal albinism phenotype despite near normal melanin synthesis. We will discuss a potential way to treat the disease and restore normal retinal development. Finally, we will briefly discuss the possibility that this same pathway may intersect with the most common cause of permanent vision loss in the elderly.

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Controlled exosome release from the retinal pigment epithelium in situ

Cited by 43 publications

References 18 publications

Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers

Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers

Roles of exosomes in the normal and diseased eye

Pigmentation and vision: Is GPR143 in control?

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