PMID- 31879569
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220412
IS  - 2164-2591 (Print)
IS  - 2164-2591 (Electronic)
IS  - 2164-2591 (Linking)
VI  - 8
IP  - 6
DP  - 2019 Nov
TI  - Topical Trabodenoson Is Neuroprotective in a Rodent Model of Anterior Ischemic 
      Optic Neuropathy (rNAION).
PG  - 47
LID - 10.1167/tvst.8.6.47 [doi]
LID - 47
AB  - PURPOSE: Nonarteritic anterior ischemic optic neuropathy (NAION) is the leading 
      cause of sudden optic nerve-related vision loss currently without effective 
      treatment. We evaluated the neuroprotective potential of ocular (topical) 
      delivery of trabodenoson, a selective A(1) receptor mimetic, in a rodent model of 
      NAION (rNAION). METHODS: Daily topical delivery of 3% trabodenoson or vehicle 
      administered in both eyes 3 days prior to rNAION induction and for 21 days post 
      induction. Retinal appearance and optic nerve head (ONH) edema was evaluated 
      using spectral-domain optical coherence tomography (SD-OCT). Retinal function was 
      evaluated before and after induction by ganzfeld electroretinography (ERG). 
      Brn3a(+) retinal ganglion cells (RGCs) were quantified by stereology. Axonal 
      ultrastructure was evaluated by electron microscopy. RESULTS: 
      Trabodenoson-treated eyes had significantly reduced optic nerve (ON) edema 
      compared with vehicle-treated eyes (ANOVA, P < 0.05). Electrophysiologically, 
      there was a nonsignificant trend toward b-wave and oscillatory potential (OP) 
      preservation in the trabodenoson-treated eyes. RGC counts were higher in 
      trabodenoson-treated eyes compared to vehicle (74% versus 47% of the 
      contralateral eye; two-tailed t-test; P = 0.01), as were ON axons. No overt 
      morphologic differences in cell inflammation were observed between vehicle- and 
      trabodenoson-treated ONHs, but trabodenoson-treated ONHs revealed increased 
      expression of astrocyte-related neuroprotective responses. CONCLUSIONS: 
      Trabodenoson preserves RGCs in the rodent NAION model. While previous clinical 
      trials focused on trabodenoson's ocular antihypertensive effect, our data suggest 
      trabodenoson's primary target may be both the retina and ONH. Selective adenosine 
      A(1) agonists may prove an appropriate neuroprotective adjunctive for 
      ischemia-related ON diseases such as NAION and glaucoma. TRANSLATIONAL RELEVANCE: 
      RGC and ON neuroprotection in ischemic neuropathies may be achievable by topical 
      administration of A(1) adenosine agonists rather than by simply relying on 
      intraocular pressure reduction.
CI  - Copyright 2019 The Authors.
FAU - Guo, Yan
AU  - Guo Y
AD  - Department of Ophthalmology and Visual Sciences, University of Maryland at 
      Baltimore-School of Medicine, Baltimore, MD, USA.
FAU - Mehrabian, Zara
AU  - Mehrabian Z
AD  - Department of Ophthalmology and Visual Sciences, University of Maryland at 
      Baltimore-School of Medicine, Baltimore, MD, USA.
FAU - Johnson, Mary A
AU  - Johnson MA
AD  - Department of Ophthalmology and Visual Sciences, University of Maryland at 
      Baltimore-School of Medicine, Baltimore, MD, USA.
FAU - Albers, David S
AU  - Albers DS
AD  - ReNeuron, Inc., Burlington, MA, USA.
FAU - Rich, Cadmus C
AU  - Rich CC
AD  - Aura Biosciences, Inc., Cambridge, MA, USA.
FAU - Baumgartner, Rudolf A
AU  - Baumgartner RA
AD  - Flatley Discovery Lab, LLC, Charlestown, MA, USA.
FAU - Bernstein, Steven L
AU  - Bernstein SL
AD  - Department of Ophthalmology and Visual Sciences, University of Maryland at 
      Baltimore-School of Medicine, Baltimore, MD, USA.
LA  - eng
GR  - R01 EY015304/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20191220
PL  - United States
TA  - Transl Vis Sci Technol
JT  - Translational vision science & technology
JID - 101595919
PMC - PMC6927734
OTO - NOTNLM
OT  - adenosine receptor mimetics
OT  - astrocytes
OT  - edema
OT  - ischemia
OT  - neuroprotection
OT  - nonarteritic anterior ischemic optic neuropathy (NAION)
OT  - optic nerve
EDAT- 2019/12/28 06:00
MHDA- 2019/12/28 06:01
PMCR- 2019/12/20
CRDT- 2019/12/28 06:00
PHST- 2019/03/05 00:00 [received]
PHST- 2019/10/20 00:00 [accepted]
PHST- 2019/12/28 06:00 [entrez]
PHST- 2019/12/28 06:00 [pubmed]
PHST- 2019/12/28 06:01 [medline]
PHST- 2019/12/20 00:00 [pmc-release]
AID - TVST-19-1477 [pii]
AID - 10.1167/tvst.8.6.47 [doi]
PST - epublish
SO  - Transl Vis Sci Technol. 2019 Dec 20;8(6):47. doi: 10.1167/tvst.8.6.47. 
      eCollection 2019 Nov.