Autophagy is an important homeostatic cellular process encompassing a
number of consecutive steps indispensable for degrading and recycling cytoplasmic
materials. Basically autophagy is an adaptive response that under stressful conditions
guarantees the physiological turnover of senescent and impaired organelles and, thus,
controls cell fate by various cross-talk signals. Diabetic retinopathy (DR) is a serious
microvascular complication of diabetes and accounts for 5% of all blindness.
Although, various metabolic disorders have been linked with the onset of DR, due to
the complex character of this multi-factorial disease, a connection between any
particular defect and DR becomes speculative. Diabetes increases inflammation,
advanced glycation end products (AGEs) and oxidative stress in the retina and its
capillary cells. Particularly, a great number of evidences suggest a mutual connection between oxidative
stress and other major metabolic abnormalities implicated in the development of DR. In addition, the
intricate networks between autophagy and apoptosis establish the degree of cellular apoptosis and the
progression of DR. Growing data underline the crucial role of reactive oxygen species (ROS) in the
activation of autophagy. Depending on their delicate balance both redox signaling and autophagy, being
detrimental or beneficial, retain opposing effects. The molecular mechanisms of autophagy are very
complex and involve many signaling pathways cooperating at various steps. This review summarizes
recent advances of the possible molecular mechanisms in autophagic process that are involved in
pathophysiology of DR. In-depth analysis on the molecular mechanisms leading to autophagy in the
retinal pigment epithelial (RPE) will be helpful to plan new therapies aimed at preventing or improving
the progression of DR.
Keywords: Damage-regulated autophagy modulator, diabetic retinopathy, mTOR deregulation, mTORC1, UPR, XBP1.
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