PMID- 32788291
OWN - NLM
STAT- MEDLINE
DCOM- 20220310
LR  - 20240229
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 62
DP  - 2021
TI  - Docosanoid signaling modulates corneal nerve regeneration: effect on tear 
      secretion, wound healing, and neuropathic pain.
PG  - 100033
LID - S0022-2275(21)00013-4 [pii]
LID - 10.1194/jlr.TR120000954 [doi]
LID - 100033
AB  - The cornea is densely innervated, mainly by sensory nerves of the ophthalmic 
      branch of the trigeminal ganglia (TG). These nerves are important to maintain 
      corneal homeostasis, and nerve damage can lead to a decrease in wound healing, an 
      increase in corneal ulceration and dry eye disease (DED), and neuropathic pain. 
      Pathologies, such as diabetes, aging, viral and bacterial infection, as well as 
      prolonged use of contact lenses and surgeries to correct vision can produce nerve 
      damage. There are no effective therapies to alleviate DED (a multifunctional 
      disease) and several clinical trials using omega-3 supplementation show unclear and 
      sometimes negative results. Using animal models of corneal nerve damage, we show 
      that treating corneas with pigment epithelium-derived factor plus DHA increases 
      nerve regeneration, wound healing, and tear secretion. The mechanism involves the 
      activation of a calcium-independent phospholipase A2 that releases the 
      incorporated DHA from phospholipids and enhances the synthesis of the 
      docosanoids, neuroprotectin D1 (NPD1) and a new resolvin stereoisomer, resolvin 
      D6i (RvD6i). NPD1 stimulates the synthesis of brain-derived neurotrophic factor, 
      nerve growth factor, and semaphorin 7A. RvD6i treatment of injured corneas 
      modulates gene expression in the TG resulting in enhanced neurogenesis, decreased 
      neuropathic pain, and increased sensitivity. Taken together, these results 
      represent a promising therapeutic option to reestablish the homeostasis of the 
      cornea.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Pham, Thang L
AU  - Pham TL
AD  - Neuroscience Center of Excellence and Department of Ophthalmology, School of 
      Medicine, Louisiana State University Health New Orleans, New Orleans, LA, USA.
FAU - Bazan, Haydee E P
AU  - Bazan HEP
AD  - Neuroscience Center of Excellence and Department of Ophthalmology, School of 
      Medicine, Louisiana State University Health New Orleans, New Orleans, LA, USA. 
      Electronic address: hbazan1@lsuhsc.edu.
LA  - eng
GR  - R01 EY019465/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20210206
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
SB  - IM
MH  - *Cornea
PMC - PMC7933495
OTO - NOTNLM
OT  - cell signaling
OT  - docosahexaenoic acid
OT  - dry eye
OT  - gene expression
OT  - lipoxygenase
OT  - neuroprotectin D1
OT  - omega 3 fatty acids
OT  - phospholipase A2
OT  - pigment epithelium-derived factor
OT  - stereoisomer of resolvin D6
COIS- Conflict of interest The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2020/08/14 06:00
MHDA- 2022/03/11 06:00
PMCR- 2021/02/06
CRDT- 2020/08/14 06:00
PHST- 2020/06/02 00:00 [received]
PHST- 2020/07/31 00:00 [revised]
PHST- 2020/08/14 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2020/08/14 06:00 [entrez]
PHST- 2021/02/06 00:00 [pmc-release]
AID - S0022-2275(21)00013-4 [pii]
AID - 100033 [pii]
AID - 10.1194/jlr.TR120000954 [doi]
PST - ppublish
SO  - J Lipid Res. 2021;62:100033. doi: 10.1194/jlr.TR120000954. Epub 2021 Feb 6.