Human Immunodeficiency Virus Type 1 Can Infect Human Retinal Pigment Epithelial Cells in Culture and Alter the Ability of the Cells to Phagocytose Rod Outer Segment Membranes

Canki, Mario; Sparrow, Janet R.; Chao, Wei; Potash, Mary Jane; Volsky, David J.

doi:10.1089/088922200309115

Cited by 16 publications

(12 citation statements)

References 68 publications

(42 reference statements)

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“…This process of general fusion between two membranes (in this case, between the exosomal and target cell membranes) is thought to occur in most cell types as a method of information exchange between cells that does not require direct intercellular contact. It has been shown that HIV is able to infect a broad spectrum of cell types, including cells that lack viral receptors such as fibroblasts (48,49), hepatocytes (50), and epithelial cells (51,52). These observations strongly support the Trojan exosome model, which predicts that many cell types will be infected at low efficiency by the uptake of HIV through the existing pathway for exosomal exchange.…”

Section: Half-maximal Signal Titers In Exosomes For Five Proteins Of mentioning

confidence: 76%

Evidence That HIV Budding in Primary Macrophages Occurs through the Exosome Release Pathway

Nguyen

Booth

Gould

et al. 2003

Journal of Biological Chemistry

297

270

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Section: Half-maximal Signal Titers In Exosomes For Five Proteins Of mentioning

confidence: 76%

Evidence That HIV Budding in Primary Macrophages Occurs through the Exosome Release Pathway

Nguyen

Booth

Gould

et al. 2003

Journal of Biological Chemistry

297

270

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“…It has been hypothesized that they may be partially responsible for loss of visual function and visual field [16-18]. A limited number of human studies have been performed with animal models providing the bulk of our knowledge on retinal gene expression to date.…”

Section: Introductionmentioning

confidence: 99%

A Degenerative Retinal Process in HIV-Associated Non-Infectious Retinopathy

et al. 2013

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HIV retinopathy is the most common non-infectious complication in the eyes of HIV-positive individuals. Oncotic lesions in the retinal nerve fiber layer, referred to as cotton wool spots (CWS), and intraretinal (IR) hemorrhages are frequently observed but are not unique to this pathology. HIV-positive patients have impaired color vision and contrast sensitivity, which worsens with age. Evidence of inner–retinal lesions and damage have been documented ophthalmoscopically, however their long term structural effect has not been investigated. It has been hypothesized that they may be partially responsible for loss of visual function and visual field. In this study we utilized clinical data, retinal imaging and transcriptomics approaches to comprehensively interrogate non-infectious HIV retinopathy. The methods employed encompassed clinical examinations, fundus photography, indirect ophthalmoscopy, Farmsworth-Munsell 100 hue discrimination testing and Illumina BeadChip analyses. Here we show that changes in the outer retina, specifically in the retinal pigment epithelium (RPE) and photoreceptor outer segments (POS) contribute to vision changes in non-infectious HIV retinopathy. We find that in HIV-positive retinae there is an induction of rhodopsin and other transcripts (including PDE6A, PDE6B, PDE6G, CNGA1, CNGB1, CRX, NRL) involved in visual transduction, as well as structural components of the rod photoreceptors (ABCA4 and ROM1). This is consistent with an increased rate of renewal of rod outer segments induced via increased phagocytosis by HIV-infected RPE previously reported in culture. Cone-specific transcripts (OPN1SW, OPN1LW, PDE6C, PDE6H and GRK7) are uniformly downregulated in HIV positive retina, likely due to a partial loss of cone photoreceptors. Active cotton wool spots and intraretinal hemorrhages (IRH) may not affect photoreceptors directly and the interaction of photoreceptors with the aging RPE may be the key to the progressive vision changes in HIV-positive patients.

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“…The RPE can ingest a variety of different particles including possible pathogens, as has been shown for yeast and molds [5,6]. Also, viral agents can have a profound effect on the phagocytic capacity of the RPE, as has recently been shown for HIV [7]. This is of special interest for the data previously presented by our group, namely that several human viruses of different virus classes are able to infect human retinal pigment cells [8] and can induce changes in surface receptor expression of immune-regulatory molecules on RPE cells [9].…”

Section: Introductionmentioning

confidence: 91%

Retinal Pigment Epithelial Phagocytosis and Metabolism Differ from Those of Macrophages

Irschick

Sgonc²,

Böck³

et al. 2004

Ophthalmic Res

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The purpose of this study is to compare primary human retinal pigment epithelium (RPE) cells with respect to particle uptake and further processing steps with immunological phagocytes for a better understanding of the possible role of RPE cells in triggering autoimmune diseases in the eye. We investigated the similarities of human RPE and monocytes/macrophages studying the uptake of fluorescein- and europium-labeled synthetic microparticles and microbial pathogens by human and bovine RPE cultures and a permanent RPE cell line (CRL). The uptake was monitored by laser scanning microscopy, flow cytometry and time-resolved fluorescence analysis; for comparison, macrophages and a macrophage-like cell line (MonoMac6) were used. A size-dependent uptake was seen in primary RPE cultures as well as in CRL, showing a preferential uptake of smaller beads followed by Staphylococcus aureus and Escherichia coli. Opsonization with serum caused a modest increase in bacteria uptake, but in contrast to macrophages, the classical complement receptors were not found on RPE cells. Living bacteria were also ingested in a time-dependent manner, but, as no intracellular overgrowth was observed, we further investigated the oxidative ability of RPE as a possible mechanism for microbial suppression. Unlike macrophages/granulocytes, no respiratory burst was detected in RPE cells, but, comparable to MonoMac6, IFN-γ induced neopterin in the human RPE. Interestingly a diurnal rhythm of phagocytosis was observed which was influenced by light exposure suggesting that RPE cells maintain their circadian rhythm also in cell culture to a certain extent. This study further demonstrates that in addition to similar phagocytic properties the RPE still shows substantial metabolic differences in comparison to blood-derived phagocytes.

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Human Immunodeficiency Virus Type 1 Can Infect Human Retinal Pigment Epithelial Cells in Culture and Alter the Ability of the Cells to Phagocytose Rod Outer Segment Membranes

Cited by 16 publications

References 68 publications

Evidence That HIV Budding in Primary Macrophages Occurs through the Exosome Release Pathway

Evidence That HIV Budding in Primary Macrophages Occurs through the Exosome Release Pathway

A Degenerative Retinal Process in HIV-Associated Non-Infectious Retinopathy

Retinal Pigment Epithelial Phagocytosis and Metabolism Differ from Those of Macrophages

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