Regulation of autophagy by high glucose in human retinal pigment epithelium.
BACKGROUND
Autophagy is a self-degradative process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. Retinal pigment epithelium (RPE) works as the outer blood retina barrier and is vulnerable to energy stress-induced injury. However, the effect of high glucose treatment on autophagy is still unclear in RPE.


METHODS
Transmission electron microscopy was used to detect the generation of autophagosome. Small interfering RNA (siRNA) and MTT was used to determine the effect of autophagy on cell viability. Western blots and immunohistochemistry were used to detect the expression pattern of autophagic markers, including LC3 and p62.


RESULTS
High glucose treatment results in a significant increase in the generation of autophagosome and altered expression of LC3 and p62. High glucose-induced autophagy is independent of mTOR signaling, but is mainly regulated via ROS-mediated ER stress signaling.


CONCLUSIONS
In the scenario of high glucose-induced oxidative stress, autophagy may be required for the removal of damaged proteins, and provide a default mechanism to prevent high glucose-induced injury in RPE.
Eye Hospital, Nanjing Medical University, Nanjing, China.
Jin
J
Yao
Zhi-Fu
ZF
Tao
Chao-Peng
CP
Li
Xiu-Miao
XM
Li
Guo-Fan
GF
Cao
Qin
Q
Jiang
Biao
B
Yan
D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D015415:Biomarkers; D017382:Reactive Oxygen Species; D058570:TOR Serine-Threonine Kinases; D005947:Glucose