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.

Grant Number: 5R21EY037078-02
NIH Institute/Center: NIH
Principal Investigator: MANUELA BARTOLI