PMID- 30004669
OWN - NLM
STAT- MEDLINE
DCOM- 20190930
LR  - 20191228
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Print)
IS  - 1936-0851 (Linking)
VI  - 12
IP  - 8
DP  - 2018 Aug 28
TI  - Multifarious Biologic Loaded Liposomes that Stimulate the Mammalian Target of 
      Rapamycin Signaling Pathway Show Retina Neuroprotection after Retina Damage.
PG  - 7497-7508
LID - 10.1021/acsnano.8b00596 [doi]
AB  - 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.
FAU - Eriksen, Anne Z
AU  - Eriksen AZ
AD  - DTU Nanotech, Department of Micro- and Nanotechnology , Technical University of 
      Denmark , 2800 Kongens Lyngby , Denmark.
FAU - Eliasen, Rasmus
AU  - Eliasen R
AD  - DTU Nanotech, Department of Micro- and Nanotechnology , Technical University of 
      Denmark , 2800 Kongens Lyngby , Denmark.
FAU - Oswald, Julia
AU  - Oswald J
AD  - Schepens Eye Research Institute, Massachusetts Eye and Ear , 20 Staniford Street 
      , Boston , Massachusetts 02114 , United States.
FAU - Kempen, Paul J
AU  - Kempen PJ
AD  - DTU Nanotech, Department of Micro- and Nanotechnology , Technical University of 
      Denmark , 2800 Kongens Lyngby , Denmark.
FAU - Melander, Fredrik
AU  - Melander F
AD  - DTU Nanotech, Department of Micro- and Nanotechnology , Technical University of 
      Denmark , 2800 Kongens Lyngby , Denmark.
FAU - Andresen, Thomas L
AU  - Andresen TL
AD  - DTU Nanotech, Department of Micro- and Nanotechnology , Technical University of 
      Denmark , 2800 Kongens Lyngby , Denmark.
FAU - Young, Michael
AU  - Young M
AD  - Schepens Eye Research Institute, Massachusetts Eye and Ear , 20 Staniford Street 
      , Boston , Massachusetts 02114 , United States.
FAU - Baranov, Petr
AU  - Baranov P
AUID- ORCID: 0000-0002-5526-7058
AD  - Schepens Eye Research Institute, Massachusetts Eye and Ear , 20 Staniford Street 
      , Boston , Massachusetts 02114 , United States.
FAU - Urquhart, Andrew J
AU  - Urquhart AJ
AUID- ORCID: 0000-0002-5322-0002
AD  - DTU Nanotech, Department of Micro- and Nanotechnology , Technical University of 
      Denmark , 2800 Kongens Lyngby , Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180718
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
RN  - 0 (Liposomes)
RN  - 0 (Neuroprotective Agents)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Liposomes
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/*pharmacology
MH  - Particle Size
MH  - Retinal Ganglion Cells/*drug effects/metabolism/pathology
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/*pharmacology
MH  - Surface Properties
PMC - PMC6117751
OTO - NOTNLM
OT  - ganglion
OT  - liposomes
OT  - neuropathy
OT  - neuroprotection
OT  - retina
OT  - transplant
COIS- The authors declare no competing financial interest.
EDAT- 2018/07/14 06:00
MHDA- 2019/10/01 06:00
PMCR- 2018/08/31
CRDT- 2018/07/14 06:00
PHST- 2018/07/14 06:00 [pubmed]
PHST- 2019/10/01 06:00 [medline]
PHST- 2018/07/14 06:00 [entrez]
PHST- 2018/08/31 00:00 [pmc-release]
AID - 10.1021/acsnano.8b00596 [doi]
PST - ppublish
SO  - ACS Nano. 2018 Aug 28;12(8):7497-7508. doi: 10.1021/acsnano.8b00596. Epub 2018 
      Jul 18.