March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Autophagy in Modified LDL-induced Pericyte Loss in Diabetic Retinopathy
Author Affiliations & Notes
  • Dongxu Fu
    Harold Hamm Oklahoma Diabetes Ctr, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Jing Zhang
    Harold Hamm Oklahoma Diabetes Ctr, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Shihe Yang
    Harold Hamm Oklahoma Diabetes Ctr, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Mei Du
    Harold Hamm Oklahoma Diabetes Ctr, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Mingyuan Wu
    Harold Hamm Oklahoma Diabetes Ctr, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Kenneth Wilson
    Harold Hamm Oklahoma Diabetes Ctr, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Junping Chen
    Harold Hamm Oklahoma Diabetes Ctr, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Timothy Lyons
    Harold Hamm Oklahoma Diabetes Ctr, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  Dongxu Fu, None; Jing Zhang, None; Shihe Yang, None; Mei Du, None; Mingyuan Wu, None; Kenneth Wilson, None; Junping Chen, None; Timothy Lyons, None
  • Footnotes
    Support  Oklahoma Center for the Advancement of Science and Technology (HR08-067),
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2437. doi:
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      Dongxu Fu, Jing Zhang, Shihe Yang, Mei Du, Mingyuan Wu, Kenneth Wilson, Junping Chen, Timothy Lyons; Autophagy in Modified LDL-induced Pericyte Loss in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2437.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Our previous studies showed that in diabetic retinopathy (DR) extravasated, modified LDL was associated with human retinal pericyte apoptosis via activation of oxidative stress and ER Stress. Autophagy is a reparative process and able to alleviate oxidative stress and ER stress, but if stress is prolonged, autophagy may lead instead to cell death. Little is known about role of autophagy in modified LDL-induced pericyte loss.

Methods: : Human retinal capillary pericytes (HRCP) were exposed (for up to 24h) to HOG-LDL vs. native LDL (N-LDL) (each at 50 or 200mg/L) with/without pretreatment with inhibitors of autophagy (3-Methyladenine, 3MA), caspase (z-VAD-fm), oxidative stress (N-Acetyl Cysteine, NAC), ER stress (4-phenyl butyric acid, 4-PBA), JNK (sp600125). Cell viability, oxidative stress, ER stress, apoptosis and autophagy were determined by methods including CCK-8 assay, western blots, immunocytochemistry and TUNEL assay.

Results: : Compared with N-LDL: (a) both doses of HOG-LDL activated oxidative stress (increased ROS, 6h), ER Stress (increased expression of KDEL, p-eIF2α and ATF6 nuclear translocation, 12h) and autophagy (increased expression of LC3II, 12h); (b) high but not low dose HOG-LDL decreased cell viability and induced apoptosis (increase expression of Bax, AIF, Cyt-C and TUNEL positive cells, 24h); however, when pretreated with 3-MA or sp600125, low dose HOG-LDL also decreased cell viability and induced apoptosis; (c) HOG-LDL induced JNK phosphorylation (12h) and increased expression of CHOP (12h); inhibition of phospho-JNK or knockdown of CHOP attenuated autophagy (12h) and apoptosis (24h) respectively.

Conclusions: : Autophagys play different roles in modified LDL-induced pericyte loss. Low dose HOG-LDL induced mild stress and anti-apoptotic effects of autophagy promoted cell survival. High dose HOG-LDL induced severe stress and autophagy was implicated in promotion of apoptosis.

Keywords: diabetic retinopathy • oxidation/oxidative or free radical damage 
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