Abstract
HIV-1-associated ocular complications, such as microvasculopathies, can lead to the loss of vision in HIV-1-infected patients. Even in patients under highly active antiretroviral therapy, ocular lesions are unavoidable. Ocular complications have been demonstrated to be closely related to the breakdown of the blood-retinal-barrier (BRB); however, the underlying mechanism is not clear. The data from this study indicated that the HIV-1 Tat protein induced the apoptosis of human retinal microvascular endothelial cells (HRMECs) and retinal pigmen epithelium (RPE) cells, which compose the inner BRB and the outer BRB, respectively. In addition, this study found that the activation of N-methyl-D-aspartate receptors (NMDARs) was involved in the apoptosis of RPE cells, but it caused no changes in HRMECs. Furthermore, both cell types exhibited enhanced expression of Bak, Bax and Cytochrome c. The inhibition of Tat activity protected against the apoptosis induced by NMDAR activation and prevented the dysregulation of Bak, Bax and Cytochrome c, revealing an important role for the mitochondrial pathway in HIV-1 Tat-induced apoptosis. Together, these findings suggest a possible mechanism and may identify a potential therapeutic strategy for HIV-1-associated ocular complications.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Neutralizing / pharmacology
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Apoptosis / drug effects*
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Blood-Retinal Barrier / cytology
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Blood-Retinal Barrier / drug effects
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Blood-Retinal Barrier / metabolism
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Cell Line
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Cytochromes c / genetics
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Cytochromes c / metabolism
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Dose-Response Relationship, Drug
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Endothelial Cells / cytology
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Gene Expression Regulation
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HIV-1 / chemistry*
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Humans
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Mitochondria / drug effects
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Mitochondria / metabolism
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Models, Biological
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Organ Specificity
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Receptors, N-Methyl-D-Aspartate / genetics
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Receptors, N-Methyl-D-Aspartate / metabolism
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Retinal Pigment Epithelium / cytology
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Retinal Pigment Epithelium / drug effects*
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Retinal Pigment Epithelium / metabolism
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Signal Transduction
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bcl-2 Homologous Antagonist-Killer Protein / genetics
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bcl-2 Homologous Antagonist-Killer Protein / metabolism
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
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tat Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors
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tat Gene Products, Human Immunodeficiency Virus / pharmacology*
Substances
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Antibodies, Neutralizing
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BAK1 protein, human
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BAX protein, human
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Receptors, N-Methyl-D-Aspartate
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bcl-2 Homologous Antagonist-Killer Protein
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bcl-2-Associated X Protein
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tat Gene Products, Human Immunodeficiency Virus
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Cytochromes c
Grants and funding
This research was supported by the National Natural Science Foundations of China (81070757, 81070737). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.