{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:09:02Z","timestamp":1792634942072,"version":"4.5.0"},"reference-count":96,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2018,8,15]],"date-time":"2018-08-15T00:00:00Z","timestamp":1534291200000},"content-version":"vor","delay-in-days":33,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EYE003790"],"award-info":[{"award-number":["P30EYE003790"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008397","name":"Velux Fonden","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100008397","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A common event in optic neuropathies is the loss of axons and death of retinal ganglion cells (RGCs) resulting in irreversible blindness. Mammalian target of rapamycin (mTOR) signaling pathway agonists have been shown to foster axon regeneration and RGC survival in animal models of optic nerve damage. However, many challenges remain in developing therapies that exploit cell growth and tissue remodeling including (i) activating\/inhibiting cell pathways synergistically, (ii) avoiding tumorigenesis, and (iii) ensuring appropriate physiological tissue function. These challenges are further exacerbated by the need to overcome ocular physiological barriers and clearance mechanisms. Here we present liposomes loaded with multiple mTOR pathway stimulating biologics designed to enhance neuroprotection after retina damage. Liposomes were loaded with ciliary neurotrophic factor, insulin-like growth factor 1, a lipopeptide N-fragment osteopontin mimic, and lipopeptide phosphatase tension homologue inhibitors for either the ATP domain or the c-terminal tail. In a mouse model of N-methyl-d-aspartic acid induced RGC death, a single intravitreal administration of liposomes reduced both RGC death and loss of retina electrophysiological function. Furthermore, combining liposomes with transplantation of induced pluripotent stem cell derived RGCs led to an improved electrophysiological outcome in mice. The results presented here show that liposomes carrying multiple signaling pathway modulators can facilitate neuroprotection and transplant electrophysiological outcome.<\/jats:p>","DOI":"10.1021\/acsnano.8b00596","type":"journal-article","created":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T17:03:30Z","timestamp":1531501410000},"page":"7497-7508","source":"Crossref","is-referenced-by-count":33,"title":["Multifarious\nBiologic Loaded Liposomes that Stimulate\nthe Mammalian Target of Rapamycin Signaling Pathway Show Retina Neuroprotection\nafter Retina Damage"],"prefix":"10.1021","volume":"12","author":[{"given":"Anne Z.","family":"Eriksen","sequence":"first","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasmus","family":"Eliasen","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Oswald","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear , 20 Staniford Street , , ,","place":["Boston, Massachusetts, United States, 02114"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Kempen","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Melander","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Andresen","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Young","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear , 20 Staniford Street , , ,","place":["Boston, Massachusetts, United States, 02114"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5526-7058","authenticated-orcid":true,"given":"Petr","family":"Baranov","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute, Massachusetts Eye and Ear , 20 Staniford Street , , ,","place":["Boston, Massachusetts, United States, 02114"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5322-0002","authenticated-orcid":true,"given":"Andrew J.","family":"Urquhart","sequence":"additional","affiliation":[{"name":"Technical University of Denmark , , ,","place":["Kongens Lyngby, Denmark, 2800"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2018,7,13]]},"reference":[{"key":"2026090222260763400_cit1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The Number of People with Glaucoma Worldwide in 2010\nand 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. 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Retinal Eye Res."},{"key":"2026090222260763400_cit5","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/npp.2013.237","article-title":"Regenerative Therapies\nfor Central Nervous System Diseases: a Biomaterials Approach","volume":"39","author":"Tam","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"2026090222260763400_cit6","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1126\/science.8235590","article-title":"Programmed Cell Death and the Control of Cell Survival:\nLessons from the Nervous System","volume":"262","author":"Raff","year":"1993","journal-title":"Science"},{"key":"2026090222260763400_cit7","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/0006-8993(93)90695-J","article-title":"Intravitreal Injections\nof Neurotrophic Factors Support\nthe Survival of Axotomized Retinal Ganglion Cells in Adult Rats In Vivo","volume":"602","author":"Mey","year":"1993","journal-title":"Brain Res."},{"key":"2026090222260763400_cit8","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1002\/jps.20629","article-title":"Neuroprotection\nof Retinal Ganglion Cells in DBA\/2J Mice with GDNF-loaded Biodegradable\nMicrospheres","volume":"96","author":"Ward","year":"2007","journal-title":"J. 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Biol. Chem."},{"key":"2026090222260763400_cit29","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1172\/JCI12980","article-title":"Osteopontin\nas a Means to Cope with Environmental Insults: Regulation of Inflammation,\nTissue Remodeling, and Cell Survival","volume":"107","author":"Denhardt","year":"2001","journal-title":"J. Clin.\nInvest."},{"key":"2026090222260763400_cit30","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/sj.jcbfm.9600022","article-title":"Neuroprotection\nby Osteopontin in Stroke","volume":"25","author":"Meller","year":"2005","journal-title":"J. Cereb. 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Chem."},{"key":"2026090222260763400_cit49","doi-asserted-by":"crossref","first-page":"20369","DOI":"10.1016\/S0021-9258(18)54932-2","article-title":"Recognition\nof Osteopontin and Related\nPeptides by an Alpha v Beta 3 Integrin Stimulates Immediate Cell Signals\nin Osteoclasts","volume":"266","author":"Miyauchi","year":"1991","journal-title":"J. Biol. Chem."},{"key":"2026090222260763400_cit50","doi-asserted-by":"publisher","first-page":"4610","DOI":"10.1016\/j.biomaterials.2014.02.037","article-title":"The Effect\nof Systemic PTEN Antagonist Peptides on Axon Growth and Functional\nRecovery after Spinal Cord Injury","volume":"35","author":"Ohtake","year":"2014","journal-title":"Biomaterials"},{"key":"2026090222260763400_cit51","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nmat2442","article-title":"Understanding Biophysicochemical\nInteractions at the\nNano-Bio Interface","volume":"8","author":"Nel","year":"2009","journal-title":"Nat. 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