Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors


Posted: 2021-11-09 20:00:00
J Extracell Vesicles . 2021 Nov;10(13):e12165. doi: 10.1002/jev2.12165. Miguel Flores-Bellver 1 , Jason Mighty 2 3 , Silvia Aparicio-Domingo 1 , Kang V Li 1 , Cui Shi 2 3 , Jing Zhou 2 , Hannah Cobb 1 , Patrick McGrath 4 , German Michelis 5 , Patricia Lenhart 1 , Ganna Bilousova 4 6 7 , Søren Heissel 8 , Michael J Rudy 9 , Christina Coughlan 10 , Andrew E Goodspeed 11 12 , S Patricia Becerra 5 , Stephen Redenti 2 3 13 , M Valeria Canto-Soler 1 6 Affiliations Expand Affiliations 1 CellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, USA. 2 Lehman College, Bronx, New York, USA. 3 Biology Doctoral Program, The Graduate School and University Center, City University of New York, New York, New York, USA. 4 Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA. 5 Section of Protein Structure and Function, NEI, NIH, Bethesda, Maryland, USA. 6 Charles C. Gates Center for Regenerative Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA. 7 Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine, Aurora, Colorado, USA. 8 Proteomics Resource Center, The Rockefeller University, New York, New York, USA. 9 Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA. 10 University of Colorado Alzheimer's and Cognition Center, Department of Neurology, Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 11 Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 12 University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 13 Biochemistry Doctoral Program, The Graduate School, City University of New York, New York, New York, USA. Item in Clipboard Miguel Flores-Bellver et al. J Extracell Vesicles. 2021 Nov. Show details Display options Display options Format J Extracell Vesicles . 2021 Nov;10(13):e12165. doi: 10.1002/jev2.12165. Authors Miguel Flores-Bellver 1 , Jason Mighty 2 3 , Silvia Aparicio-Domingo 1 , Kang V Li 1 , Cui Shi 2 3 , Jing Zhou 2 , Hannah Cobb 1 , Patrick McGrath 4 , German Michelis 5 , Patricia Lenhart 1 , Ganna Bilousova 4 6 7 , Søren Heissel 8 , Michael J Rudy 9 , Christina Coughlan 10 , Andrew E Goodspeed 11 12 , S Patricia Becerra 5 , Stephen Redenti 2 3 13 , M Valeria Canto-Soler 1 6 Affiliations 1 CellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, USA. 2 Lehman College, Bronx, New York, USA. 3 Biology Doctoral Program, The Graduate School and University Center, City University of New York, New York, New York, USA. 4 Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA. 5 Section of Protein Structure and Function, NEI, NIH, Bethesda, Maryland, USA. 6 Charles C. Gates Center for Regenerative Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA. 7 Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine, Aurora, Colorado, USA. 8 Proteomics Resource Center, The Rockefeller University, New York, New York, USA. 9 Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA. 10 University of Colorado Alzheimer's and Cognition Center, Department of Neurology, Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 11 Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 12 University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 13 Biochemistry Doctoral Program, The Graduate School, City University of New York, New York, New York, USA. Item in Clipboard CiteDisplay options Display options Format Abstract Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen-associated proteins are released as cargo of extracellular vesicles secreted by RPE cells in a polarised apical:basal mode. Notably, drusen-associated proteins exhibited distinctive directional secretion modes in homeostatic conditions and, differential modulation of this directional secretion in response to AMD stressors. These observations underpin the existence of a finely-tuned mechanism regulating directional apical:basal sorting and secretion of drusen-associated proteins via EVs, and its modulation in response to mechanisms involved in AMD pathophysiology. Collectively, our results strongly support an active role of RPE-derived EVs as a key source of drusen proteins and important contributors to drusen development and growth. Keywords: AMD; RPE; drusen; exosomes; extracellular vesicles; microvesicles; proteomics; stem cells. © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles. References REFERENCES Adler, R., & Canto-Soler, M. V. (2007). Molecular mechanisms of optic vesicle development: Complexities, ambiguities and controversies. Developmental Biology, 305, 1-13. https://doi.org/10.1016/j.ydbio.2007.01.045 Alvarez-Erviti, L., Seow, Y., Schapira, A. H., Gardiner, C., Sargent, I. L., Wood, M. J. A., & Cooper, J. M. (2011). Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiology of Disease, 42, 360-367. https://doi.org/10.1016/j.nbd.2011.01.029 Ambati, J., Ambati, B. K., Yoo, S. H., Ianchulev, S., & Adamis, A. P. (2003). Age-related macular degeneration: Etiology, pathogenesis, and therapeutic strategies. Survey of Ophthalmology, 48, 257-293. https://doi.org/10.1016/S0039-6257(03)00030-4 Ambati, J., & Fowler, B. J. (2012). Mechanisms of age-related macular degeneration. Neuron, 75, 26-39. https://doi.org/10.1016/j.neuron.2012.06.018 Anderson, D. H., Talaga, K. C., Rivest, A. J., Barron, E., Hageman, G. S., & Johnson, L. V. (2004). Characterization of beta amyloid assemblies in drusen: The deposits associated with aging and age-related macular degeneration. Experimental Eye Research, 78, 243-256. https://doi.org/10.1016/j.exer.2003.10.011 Show all 140 references Grant support Show all 8 grants [x] Cite Copy Format: Send To [x]

参考サイト PubMed: exsome



バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
6月 20, 2019 バイオアソシエイツ

移植幹細胞由来エクソソームは心臓発作からの回復を助ける。移植細胞からの循環エキソソーム解析(液体生検)は医師が回復の程度を把握することを可能にする。

心筋の強化や他の疾患を治療する幹細胞療法は、ヒト臨床試験で有望視され始めている。 しかし、臨床成果の観察以外に、標的臓器内の移植細胞の有効性を評価するうえで再現性の欠如や使用期限、非侵襲的なツールの欠如は、幹細胞分野の進歩を遅らせてきた。 メリーランド大学医学部(UMSOM)、ペンシルバニア大学、およびエモリー大学の研究者らは、移植された幹細胞の有効性を追跡するのに血液検査が使用できると理論づけた。 彼らは、移植幹細胞からレシピエントの血液に分泌される エクソソーム と呼ばれる微小な細胞成分を分析した。…

ゲスト 929人 と メンバー 4人 がオンラインです