Chronic HIV infection and ischemic retinopathies

PROJECT SUMMARY The overall goal of this novel exploratory proposal is to investigate/assess the potential impact of chronic HIV infection and /or anti-HIV drugs on the development and progression of ischemic retinopathies. Combinatorial- antiviral therapies (cART) have increased the life-expectancy of people living with HIV (PLWH), however these patients carry not-detectable levels of virus that generate chronic inflammation leading to accelerated aging and neurovascular dysfunction. Consequently, while HIV-related pathologies in immunocompromised patients are in sharp decline, there is a significant increase in metabolic and cardiovascular morbidity and mortality in PLWH. On the other hand, the contribution of long-term effects of cART as potential risk factor for cardiovascular complications in PLWH is also still unclear. Ischemic retinopathies, that comprise known leading causes of blindness (e.g. diabetic retinopathy and age-related macular degeneration), are associated with neurovascular dysfunction and accelerated cellular senescence, thus implying that individuals presenting risk factors for the occurrence of these pathogenic mechanisms, such as PLWH, could be at increased risk of developing more aggressive forms of these diseases. Our preliminary studies, conducted in an experimental model recapitulating chronic HIV infection (Tg26) and in mice treated with the nucleoside inverse transcriptase emtricitabine (FTC), show significant structural changes of the retinal vasculature accompanied by increased retinal inflammation and senescence markers. Therefore, herein we propose studies to validate our hypothesis that chronic HIV infections and/or cART treatment accelerate and complicate the occurrence and progression of ischemic retinopathies. Our aims are: Aim 1 Determine the neurovascular effects of chronic HIV infection on retinal neurovascular integrity and in response to ischemia/reperfusion injury. Aim 2 Determine the neurovascular effects of anti-HIV drugs on retinal neurovascular integrity and in response to ischemia/reperfusion injury.