Autophagy in Diabetic Retinopathy

Abstract

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.

High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway

“…Mitophagy is the selective degradation of mitochondria by autophagy and is critical for cells to maintain mitochondrial quality under environmental stress [8], which helps to protect cells from apoptosis and promote cell survival [9]. Recent study showed that DR progression is closely related with mitophagy, which prevents cells from apoptosis and alleviates DR development [10]. In addition, high glucose has been reported to impair autophagy and mitophagy in Neuro-2a cells [11], and induce retinal pericyte apoptosis and death [12], but there are no reports on low glucose’s effects on cell mitophagy and apoptosis.…”

Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm

“…Diabetic retinopathy consists of non-symptomatic non-proliferative first stage retinopathy, followed by second stage proliferative neovascularization. The proliferative stage consists of extensive angiogenesis of leakage-prone blood vessels [163] driven by HIF1a-induced VEGF. HIF1a may be induced under normoxic conditions by hyperactive mTORC1 [164,165].…”

Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer

“…Autophagy can be involved in a number of degenerative disorders such as Alzheimer's disease (42-46), Parkinson's disease (41, 47, 48), Huntington's disease (49-51), and diabetes mellitus (12, 18, 33, 43, 52, 53). Importantly, autophagy also can impact cognitive decline (12, 54, 55) and aging processes (43, 56-60).…”