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.
Highlights
Despite the advent of highly active antiretroviral therapy (HAART), ocular lesions still occur as complications in HIV patients
The BRB is composed of human retinal microvascular endothelial cells (HRMECs) and retinal pigment epithelium (RPE), which provide a dynamic barrier that regulate the bidirectional movement of signals responsible for the control of eye homeostasis [5,6,7]
We found that the HIV-1 Tat protein could induce the apoptosis of HRMECs and RPE cells in vitro, and the inhibition of Tat abrogated this Tat-induced apoptosis, implying a specific apoptosis effect of Tat on HRMECs and RPE cells
Summary
Despite the advent of highly active antiretroviral therapy (HAART), ocular lesions still occur as complications in HIV patients. A detectable HIV-1 viral load has been found in tears, even in patients under long-term HAART who have an undetectable plasma viral load [4]. This finding prompts the question: how does HIV-1 induce the break-down of the bloodretinal-barrier (BRB) and invade ocular tissues?. The capillaries of the choroid are fenestrated and contain especially large pores, which are highly permeable to glucose and to low-molecular-weight substances, thereby facilitating transport across the RPE to the retina [9]. We hypothesized that HIV-1 moves across the RPE to invade the ocular tissues, and the persistence of HIV-1 in the eye may lead to the formation of an ocular reservoir
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