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Although significant vision loss in endophthalmitis has been linked to retinal cell death, the underlying mechanisms of cell death remain elusive. In this study, using a mouse model of <jats:italic>Staphylococcus aureus<\/jats:italic> endophthalmitis and cultured human retinal M\u00fcller glia (MIO-M1 cell line), we demonstrate that <jats:italic>S. aureus<\/jats:italic> caused significant apoptotic cell death in the mouse retina and M\u00fcller glia, as evidenced by increased number of terminal dUTP nick end labeling and Annexin V and propidium iodide-positive cells. Immunohistochemistry and western blot studies revealed the reduction in mitochondrial membrane potential (JC-1 staining), release of cytochrome <jats:italic>c<\/jats:italic> into the cytosol, translocation of Bax to the mitochondria and the activation of caspase-9 and -3 in <jats:italic>S. aureus-<\/jats:italic>infected retina\/retinal cells. In addition, the activation of PARP-1 and the release of apoptosis inducing factor from mitochondria was also observed in <jats:italic>S. aureus<\/jats:italic>-infected retinal cells. Inhibition studies using pan-caspase (Q-VD-OPH) and PARP-1 (DPQ) inhibitors showed significant reduction in <jats:italic>S. aureus<\/jats:italic>-induced retinal cell death both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Together, our findings demonstrate that in bacterial endophthalmitis, retinal cells undergo apoptosis in the both caspase-dependent and independent manners, and mitochondria have a central role in this process. Hence, targeting the identified signaling pathways may provide the rationale to design therapeutic interventions to prevent bystander retinal tissue damage in bacterial endophthalmitis.<\/jats:p>","DOI":"10.1038\/cddiscovery.2016.34","type":"journal-article","created":{"date-parts":[[2016,5,30]],"date-time":"2016-05-30T07:59:45Z","timestamp":1464595185000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis"],"prefix":"10.1038","volume":"2","author":[{"given":"P K","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,30]]},"reference":[{"key":"BFcddiscovery201634_CR1","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/01926230701320337","volume":"35","author":"S Elmore","year":"2007","unstructured":"Elmore S . 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