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Recent studies have suggested that rho-associated protein kinase (ROCK) inhibitors may enhance autophagy in neurodegenerative diseases and promote the survival of RPE cells. This study investigated the effect of ROCK inhibitors on autophagy gene expression and autophagic vacuole formation in a human RPE (ARPE-19) cell line. The highly selective and potent ROCK inhibitor Y-39983 enhanced the expression of autophagy genes in ARPE-19 cells and increased autophagic vacuole formation. A proteomic analysis using mass spectrometry was performed to further characterize the effects of ROCK inhibition at the protein level. Y-39983 downregulated thrombospondin-1 (THBS1), and suppression of THBS1 in ARPE-19 cells resulted in an increase in autophagic vacuole formation. Our data showed that ROCK inhibitor-induced autophagy was mediated by THBS1 downregulation. We identified ROCK and THBS1 as potential novel therapeutic targets in AMD.<\/jats:p>","DOI":"10.3390\/cells13221907","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T13:03:14Z","timestamp":1731934994000},"page":"1907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Thrombospondin 1 Mediates Autophagy Upon Inhibition of the Rho-Associated Protein Kinase Inhibitor"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6458-4875","authenticated-orcid":false,"given":"Kirk Patrick Carreon","family":"Catral","sequence":"first","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choi-Yee","family":"Tse","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hong Kong, 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