Dual Switch Mechanism of Erythropoietin as an Antiapoptotic and Pro-Angiogenic Determinant in the Retina

Faith Pwaniyibo Samson, Weilue He, Srinivas R. Sripathi, Ambrose Teru Patrick, Joshua Madu, Hyewon Chung, Megan C. Frost, Donghyun Jee, Diana R. Gutsaeva, Wan Jin Jahng

Research output: Contribution to journalArticle

Abstract

Constant or intense light degenerates the retina and retinal pigment epithelial cells. Light generates reactive oxygen species and nitric oxide leading to initial reactions of retinal degeneration. Apoptosis is the primary mechanism of abnormal death of photoreceptors, retinal ganglion cells, or retinal pigment epithelium (RPE) in degenerative retinal diseases, including diabetic retinopathy and age-related macular degeneration. The current study evaluated the function of erythropoietin (EPO) on angiogenesis and apoptosis in the retina and RPE under oxidative stress. We determined the pro-angiogenic and antiapoptotic mechanism of EPO under stress conditions using a conditional EPO knockdown model using siRNA, EPO addition, proteomics, immunocytochemistry, and bioinformatic analysis. Our studies verified that EPO protected retinal cells from light-, hypoxia-, hyperoxia-, and hydrogen peroxide-induced apoptosis through caspase inhibition, whereas up-regulated angiogenic reactions through vascular endothelial growth factor (VEGF) and angiotensin pathway. We demonstrated that the EPO expression in the retina and subsequent serine/threonine/tyrosine kinase phosphorylations might be linked to oxidative stress response tightly to determining angiogenesis and apoptosis. Neuroprotective roles of EPO may involve the balance between antiapoptotic and pro-angiogenic signaling molecules, including BCL-xL, c-FOS, caspase-3, nitric oxide, angiotensin, and VEGF receptor. Our data indicate a new therapeutic application of EPO toward retinal degeneration based on the dual roles in apoptosis and angiogenesis at the molecular level under oxidative stress.

Original languageEnglish (US)
Pages (from-to)21113-21126
Number of pages14
JournalACS Omega
Volume5
Issue number33
DOIs
StatePublished - Aug 25 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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    Samson, F. P., He, W., Sripathi, S. R., Patrick, A. T., Madu, J., Chung, H., Frost, M. C., Jee, D., Gutsaeva, D. R., & Jahng, W. J. (2020). Dual Switch Mechanism of Erythropoietin as an Antiapoptotic and Pro-Angiogenic Determinant in the Retina. ACS Omega, 5(33), 21113-21126. https://doi.org/10.1021/acsomega.0c02763