PMID- 29847652
OWN - NLM
STAT- MEDLINE
DCOM- 20190220
LR  - 20190320
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 59
IP  - 6
DP  - 2018 May 1
TI  - RGC Neuroprotection Following Optic Nerve Trauma Mediated By Intranasal Delivery 
      of Amnion Cell Secretome.
PG  - 2470-2477
LID - 10.1167/iovs.18-24096 [doi]
AB  - PURPOSE: Intranasally delivered ST266, the biological, proteinaceous secretome of 
      amnion-derived multipotent progenitor cells, reduces retinal ganglion cell (RGC) 
      loss, optic nerve inflammation, and demyelination in experimental optic neuritis. 
      This unique therapy and novel administration route delivers numerous cytokines 
      and growth factors to the eye and optic nerve, suggesting a potential to also 
      treat other optic neuropathies. Thus, ST266-mediated neuroprotection was examined 
      following traumatic optic nerve injury. METHODS: Optic nerve crush injury was 
      surgically induced in C57BL/6J mice. Mice were treated daily with intranasal PBS 
      or ST266. RGC function was assessed by optokinetic responses (OKRs), RGCs were 
      counted, and optic nerve sections were stained with luxol fast blue and 
      anti-neurofilament antibodies to assess myelin and RGC axon damage. RESULTS: 
      Intranasal ST266 administered daily for 5 days, beginning at the time that a 
      1-second optic nerve crush was performed, significantly attenuated OKR decreases. 
      Furthermore, ST266 treatment reduced damage to RGC axons and myelin within optic 
      nerves, and blocked RGC loss. Following a 4-second optic nerve crush, intranasal 
      ST266 increased RGC survival and showed a trend toward reduced RGC axon and 
      myelin damage. Ten days following optic nerve crush, ST266 prevented myelin 
      damage, while also inducing a trend toward increased RGC survival and visual 
      function. CONCLUSIONS: ST266 significantly attenuates traumatic optic neuropathy. 
      Neuroprotective effects of this unique combination of biologic molecules observed 
      here and previously in optic neuritis suggest potential broad application for 
      preventing neuronal damage in multiple optic nerve disorders. Furthermore, 
      results support intranasal delivery as a novel, noninvasive therapeutic modality 
      for eyes and optic nerves.
FAU - Grinblat, Gabriela A
AU  - Grinblat GA
AD  - Perelman School of Medicine, University of Pennsylvania, Philadelphia, 
      Pennsylvania, United States.
FAU - Khan, Reas S
AU  - Khan RS
AD  - Scheie Eye Institute and F.M. Kirby Center for Molecular Ophthalmology, 
      University of Pennsylvania, Philadelphia, Pennsylvania, United States.
FAU - Dine, Kimberly
AU  - Dine K
AD  - Scheie Eye Institute and F.M. Kirby Center for Molecular Ophthalmology, 
      University of Pennsylvania, Philadelphia, Pennsylvania, United States.
FAU - Wessel, Howard
AU  - Wessel H
AD  - Noveome Biotherapeutics, Inc., Pittsburgh, Pennsylvania, United States.
FAU - Brown, Larry
AU  - Brown L
AD  - Noveome Biotherapeutics, Inc., Pittsburgh, Pennsylvania, United States.
FAU - Shindler, Kenneth S
AU  - Shindler KS
AD  - Scheie Eye Institute and F.M. Kirby Center for Molecular Ophthalmology, 
      University of Pennsylvania, Philadelphia, Pennsylvania, United States.
LA  - eng
GR  - R01 EY019014/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Cytokines)
RN  - 0 (Neuroprotective Agents)
SB  - IM
MH  - Administration, Intranasal
MH  - Amnion/*metabolism
MH  - Animals
MH  - Axons/drug effects
MH  - Cell Survival/drug effects
MH  - Cytokines/*administration & dosage
MH  - Disease Models, Animal
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myelin Sheath/metabolism
MH  - Nerve Crush
MH  - Neuroprotection/*drug effects
MH  - Neuroprotective Agents/*administration & dosage
MH  - Nystagmus, Optokinetic/physiology
MH  - Optic Nerve Injuries/*drug therapy/physiopathology
MH  - Retinal Ganglion Cells/*drug effects
PMC - PMC5959511
EDAT- 2018/05/31 06:00
MHDA- 2019/03/21 06:00
PMCR- 2018/05/01
CRDT- 2018/05/31 06:00
PHST- 2018/05/31 06:00 [entrez]
PHST- 2018/05/31 06:00 [pubmed]
PHST- 2019/03/21 06:00 [medline]
PHST- 2018/05/01 00:00 [pmc-release]
AID - 2681860 [pii]
AID - IOVS-18-24096R1 [pii]
AID - 10.1167/iovs.18-24096 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2470-2477. doi: 
      10.1167/iovs.18-24096.