The PI3K–PTEN tug-of-war, oxidative stress and retinal degeneration

The retinal pigment epithelium (RPE) is indispensable for photoreceptor function, not only because it provides functional photopigments to photoreceptors, but also because it eliminates oxidatively damaged materials from photoreceptors. Maintaining homeostatic antioxidative programs that support a healthy RPE is therefore important for the normal functioning of the eye. These homeostatic mechanisms, however, often fail in aged RPE cells that have been exposed repeatedly to excessive oxidative stress. When RPE cells succumb to oxidative stress, their death contributes to the development of retinal degenerative diseases such as age-related macular degeneration. Recent studies have highlighted the importance of reciprocal phosphoinositide signaling events orchestrated by phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) in the homeostatic programs that protect RPE cells against oxidative stress. Here, we discuss the role of PI3K signaling pathways in RPE cells and suggest that they might be crucial targets of oxidative molecules that initiate early pathological events in retinal degenerative diseases.