Disturbed glucose metabolism and oxidative stress through PI3K/AKT signaling pathway in HIV-1 TAT activated retinal Müller glia.

Müller glia are pivotal in providing a pro-survival environment for retinal cells and a sustainable energy metabolism is essential for upholding Müller glia functions. Changes in metabolic shifts impact on immune cell physiology. HIV-associated chronic, low-grade inflammation disrupts the metabolic machinery of the immune system promoting a state of neurodegeneration, and can also contribute to comorbidities. Here we show in an in vitro model of retinal Müller glia, induction of highly glycolytic activity upon activation. Increased oxidative stress in recombinant HIV-1 TAT activated Müller glia start as early changes, reflected in Redox functions, mitochondrial staining and 8 hydroxy 2-deoxy guanosine. Glucose transporter 1 expression, glucose uptake and glycolytic activity prominently increase in activated cells. This is also reflected in the microarray data where genes associated with metabolism and mitochondrial function along with those associated with aging are differentially regulated in activated Müller glia. In Müller glia, Glut 1 and IL1 increase with TAT. Transcriptomic data in activated Müller glia show changes in the PI3K/AKT pathway. Inhibition of PI3K/AKT reverses this increase. A clearer insight into metabolic changes in the presence of inflammatory signals at the retina can aid in understanding HIV associated retinal comorbidities.