Abstract
Age-related macular degeneration (AMD) and diabetic retinopathy (DR), leading causes of blindness, share a common retinal environment: hypoxia which is a major stimulator for the upregulation of vascular endothelial growth factor (VEGF), a cardinal pathogenic factor for the breakdown of blood-retina barrier (BRB). As a result of intensive studies on VEGF pathobiology, anti-VEGF strategy has become a major therapeutics for wet AMD and DR. To investigate the potential impact of anti-VEGF strategy on major retinal supporting cells, Müller glia (MG), we disrupted VEGF receptor-2 (VEGFR2) in MG with conditional knockout (CKO) and examined the effect of VEGFR2-null on MG viability and neuronal integrity in mice. VEGFR2 CKO mice demonstrated a significant loss of MG density in diabetes/hypoxia, which in turn resulted in accelerated retinal degeneration. These defects appear similar to the clinical characteristics in a significant portion of wet-AMD patients with long-term anti-VEGF therapies. In this article, we will discuss the potential relevance of these clinical characteristics to the critical role of VEGF signaling in MG viability and neuronal integrity in hypoxia.
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Acknowledgment
We thank Dr. V. P. Sarthy for providing rMC1 cells. Our work was supported by NIH grants GM104934, EY020900, and EY26970 and grants from Research to Prevent Blindness, International Retinal Research Foundation, Presbyterian Health Foundation, Oklahoma Center for the Advancement of Science and Technology, and Oklahoma Center for Adult Stem Cell Research and an endowment from Choctaw Nation.
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Fu, S., Dong, S., Zhu, M., Le, YZ. (2018). VEGF as a Trophic Factor for Müller Glia in Hypoxic Retinal Diseases. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_58
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DOI: https://doi.org/10.1007/978-3-319-75402-4_58
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