Endothelial Caspase-9 Mediates Inflammatory and Vision Function Changes in Retinal Vascular Injury
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Description
Retinal vein occlusion (RVO) induces pathological consequences including retinal edema, capillary ischemia, and neurodegeneration. In a mouse model of RVO, non-apoptotic expression of endothelial caspase-9 (EC Casp9) can be observed. Knockout of EC Casp9 leads to a decrease in RVO-induced pathology. In this presentation, Crystal Colón Ortiz will describe this mouse model of RVO and discuss known roles of caspases and glial cells in the retina and during vascular injury. Crystal will present a recent study that reveals that at early time-points post-RVO, EC Casp9 mediates glial changes and promotes high levels of pro-inflammatory cytokines. Behaviorally, this results in contrast sensitivity decline in these animals.
Key Topics
Endothelial caspase-9…
- leads to increases in reactive microglia
- triggers astroglial caspase-6 and cleavage of GFAP in RVO
- deletion reduces the expression of inflammatory cytokines and rescues contrast sensitivity decline one day post-RVO
Learning Objectives
You will learn about the inflammatory role of endothelial caspase-9 in neurovascular injury and its contribution to vision changes.
Background Reading
Endothelial activation of caspase-9 promotes neurovascular injury in retinal vein occlusion. Avrutsky MI, Ortiz CC, Johnson KV, Potenski AM, Chen CW, Lawson JM, White AJ, Yuen SK, Morales FN, Canepa E, Snipas S, Salvesen GS, Jean YY, Troy CM
Nat Commun. 2020 Jun 23;11(1):3173.
doi: 10.1038/s41467-020-16902-5.
A pharmacological approach in newly established retinal vein occlusion model Fuma S, Nishinaka A, Inoue Y, Tsuruma K, Shimazawa M, Kondo M, Hara H.
Sci Rep. 2017 Mar 2;7:43509.
doi: 10.1038/srep43509.
Review:
Caspase-9: A Multimodal Therapeutic Target With Diverse Cellular Expression in Human Disease Avrutsky MI, Troy CM.
Front Pharmacol. 2021 Jul 9;12:701301.
doi: 10.3389/fphar.2021.701301.
About the speaker
Crystal Colón Ortiz, Ph.D.
Graduate Student
Columbia University Medical Center
Crystal was born and raised in Puerto Rico and recently defended her PhD thesis in the lab of Dr. Carol Troy at Columbia University Irving Medical Center. She conducted studies on understanding the role of caspases in a model of retinal vascular injury. During her graduate trajectory, she was awarded with NSF-Graduate Research Fellowship Program, the Association for the American Advancement of Science (AAAS) Program for Excellence in Science, the Society for Neuroscience (SfN) Trainee Professional Development Award, and the NIH Blueprint Diversity Specialized Predoctoral to Postdoctoral Advancement in Neuroscience (D-SPAN) Award. Crystal will join Dr. Cagla Eroglu’s lab at Duke University to continue her studies as postdoctoral researcher on the retina-brain connection and neuroimmune interactions.
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Q&A from the presentation
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