PMID- 36555236
OWN - NLM
STAT- MEDLINE
DCOM- 20230103
LR  - 20230501
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 24
DP  - 2022 Dec 9
TI  - Decreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal 
      Neovascularization.
LID - 10.3390/ijms232415595 [doi]
LID - 15595
AB  - Neovascular or "wet" age-related macular degeneration (nAMD) is a leading cause 
      of blindness among older adults. Choroidal neovascularization (CNV) is a major 
      pathological feature of nAMD, in which abnormal new blood vessel growth from the 
      choroid leads to irreversible vision loss. There is a critical need to develop 
      novel therapeutic strategies to address limitations of the current anti-vascular 
      endothelial growth factor biologics. Previously, we identified soluble epoxide 
      hydrolase (sEH) as a possible therapeutic target for CNV through a forward 
      chemical genetic approach. The purpose of this study was to validate sEH as a 
      target by examining retinal expression of sEH protein and mRNA by 
      immunohistochemistry and RNAscope in situ hybridization, respectively, and to 
      assess the efficacy of an adeno-associated virus (AAV) vector designed to knock 
      down the sEH gene, Ephx2, in the murine laser-induced (L-) CNV model. nAMD 
      patient postmortem eye tissue and murine L-CNV showed overexpression of sEH in 
      photoreceptors and retinal pigment epithelial cells. Ephx2 knockdown 
      significantly reduced CNV and normalized mRNA expression levels of CNV-related 
      inflammatory markers. Thus, this study further establishes sEH as a promising 
      therapeutic target against CNV associated with nAMD.
FAU - Park, Bomina
AU  - Park B
AUID- ORCID: 0000-0003-1440-7066
AD  - Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana 
      University School of Medicine, Indianapolis, IN 46202, USA.
AD  - Department of Pharmacology and Toxicology, Indiana University School of Medicine, 
      Indianapolis, IN 46202, USA.
FAU - Sardar Pasha, Sheik Pran Babu
AU  - Sardar Pasha SPB
AD  - Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana 
      University School of Medicine, Indianapolis, IN 46202, USA.
FAU - Sishtla, Kamakshi L
AU  - Sishtla KL
AUID- ORCID: 0000-0002-1525-0155
AD  - Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana 
      University School of Medicine, Indianapolis, IN 46202, USA.
FAU - Hartman, Gabriella D
AU  - Hartman GD
AUID- ORCID: 0000-0002-2061-411X
AD  - Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana 
      University School of Medicine, Indianapolis, IN 46202, USA.
AD  - Stark Neurosciences Research Institute, Indiana University School of Medicine, 
      Indianapolis, IN 46202, USA.
FAU - Qi, Xiaoping
AU  - Qi X
AD  - Department of Ophthalmology and Visual Sciences, University of Alabama at 
      Birmingham, Birmingham, AL 35294, USA.
FAU - Boulton, Michael E
AU  - Boulton ME
AUID- ORCID: 0000-0002-0796-1766
AD  - Department of Ophthalmology and Visual Sciences, University of Alabama at 
      Birmingham, Birmingham, AL 35294, USA.
FAU - Corson, Timothy W
AU  - Corson TW
AUID- ORCID: 0000-0002-1402-7875
AD  - Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana 
      University School of Medicine, Indianapolis, IN 46202, USA.
AD  - Department of Pharmacology and Toxicology, Indiana University School of Medicine, 
      Indianapolis, IN 46202, USA.
AD  - Stark Neurosciences Research Institute, Indiana University School of Medicine, 
      Indianapolis, IN 46202, USA.
AD  - Department of Biochemistry and Molecular Biology, Indiana University School of 
      Medicine, Indianapolis, IN 46202, USA.
LA  - eng
GR  - R01EY031939/EY/NEI NIH HHS/United States
GR  - R01EY025641/EY/NEI NIH HHS/United States
GR  - R01 EY025641/EY/NEI NIH HHS/United States
GR  - R01 EY031939/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20221209
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - 0 (RNA, Messenger)
RN  - EC 3.3.2.10 (Ephx2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Choroid/metabolism
MH  - *Choroidal Neovascularization/metabolism
MH  - Disease Models, Animal
MH  - *Epoxide Hydrolases/genetics/metabolism
MH  - Mice, Inbred C57BL
MH  - Retina/metabolism
MH  - RNA, Messenger/genetics/metabolism
PMC - PMC9779010
OTO - NOTNLM
OT  - RNAscope
OT  - adenoassociated viral vector
OT  - choroidal neovascularization
OT  - neovascular age-related macular degeneration
OT  - soluble epoxide hydrolase
COIS- T.W.C. is a named inventor on patent applications related to this work and has 
      received research funding and consulting fees for related work from Evergreen 
      Therapeutics. This work received in-kind support (AAV vectors) from Biomotiv LLC. 
      The other authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript; or in the decision to publish the results.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/27 06:00
PMCR- 2022/12/09
CRDT- 2022/12/23 01:32
PHST- 2022/10/15 00:00 [received]
PHST- 2022/12/02 00:00 [revised]
PHST- 2022/12/06 00:00 [accepted]
PHST- 2022/12/23 01:32 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/27 06:00 [medline]
PHST- 2022/12/09 00:00 [pmc-release]
AID - ijms232415595 [pii]
AID - ijms-23-15595 [pii]
AID - 10.3390/ijms232415595 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Dec 9;23(24):15595. doi: 10.3390/ijms232415595.