PMID- 38036037
OWN - NLM
STAT- MEDLINE
DCOM- 20240122
LR  - 20240328
IS  - 1098-8823 (Print)
IS  - 1098-8823 (Linking)
VI  - 170
DP  - 2024 Feb
TI  - A new R,R-RvD6 isomer with protective actions following corneal nerve injury.
PG  - 106802
LID - S1098-8823(23)00099-0 [pii]
LID - 10.1016/j.prostaglandins.2023.106802 [doi]
AB  - The transparent cornea is the most densely innervated tissue in the body, 
      primarily by sensory nerves originating from the trigeminal ganglia (TG). Damage 
      to corneal nerves reduces sensitivity and tear secretion and results in dry eye. 
      Consequently, ocular pain, for which no satisfactory therapies exist, arises in 
      many cases. Treatment of injured corneas with pigment epithelium-derived factor 
      (PEDF) combined with docosahexaenoic acid (DHA) stimulates nerve regeneration in 
      models of refractive surgery, which damages nerves. The mechanism involves the 
      synthesis of a stereoisomer of resolvin D6 (R,R-RvD6) formed after incorporating 
      DHA into membrane lipids. Activation of a PEDF receptor (PEDF-R) with 
      phospholipase activity releases DHA to synthesize the new resolvin isomer, which 
      is secreted via tears. Topical treatment of mice corneas with R,R-RvD6 shows 
      higher bioactivity in regenerating nerves and increasing sensitivity compared to 
      PEDF+DHA. It also stimulates a transcriptome in the TG that modulates genes 
      involved in ocular pain. Our studies suggest an important therapeutic role for 
      R,R-RvD6 in regenerating corneal nerves and decreasing pain resulting from dry 
      eye.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Bazan, Haydee E P
AU  - Bazan HEP
AD  - Neuroscience Center of Excellence and Department of Ophthalmology, School of 
      Medicine, Louisiana State University Health Sciences Center New Orleans, New 
      Orleans, LA, USA. Electronic address: hbazan1@lsuhsc.edu.
FAU - Pham, Thang L
AU  - Pham TL
AD  - Neuroscience Center of Excellence and Department of Ophthalmology, School of 
      Medicine, Louisiana State University Health Sciences Center New Orleans, New 
      Orleans, LA, USA. Electronic address: thang@bioturing.com.
LA  - eng
GR  - R01 EY019465/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20231129
PL  - United States
TA  - Prostaglandins Other Lipid Mediat
JT  - Prostaglandins & other lipid mediators
JID - 9808648
RN  - 25167-62-8 (Docosahexaenoic Acids)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Cornea/innervation/physiology/surgery
MH  - Docosahexaenoic Acids/pharmacology/therapeutic use
MH  - Nerve Regeneration/physiology
MH  - Pain/drug therapy
MH  - *Dry Eye Syndromes/drug therapy
PMC - PMC10966988
MID - NIHMS1951844
OTO - NOTNLM
OT  - Cornea innervation
OT  - Docosahexaenoic acid
OT  - Dry eye-like pain
OT  - Pigment epithelium-derived factor
OT  - R,R-RvD6
OT  - Refractive surgery
COIS- Conflict of Interest The authors declare that there is no conflict of interest.
EDAT- 2023/12/01 00:43
MHDA- 2024/01/22 06:43
PMCR- 2025/02/01
CRDT- 2023/11/30 21:54
PHST- 2023/09/15 00:00 [received]
PHST- 2023/11/05 00:00 [revised]
PHST- 2023/11/27 00:00 [accepted]
PHST- 2025/02/01 00:00 [pmc-release]
PHST- 2024/01/22 06:43 [medline]
PHST- 2023/12/01 00:43 [pubmed]
PHST- 2023/11/30 21:54 [entrez]
AID - S1098-8823(23)00099-0 [pii]
AID - 10.1016/j.prostaglandins.2023.106802 [doi]
PST - ppublish
SO  - Prostaglandins Other Lipid Mediat. 2024 Feb;170:106802. doi: 
      10.1016/j.prostaglandins.2023.106802. Epub 2023 Nov 29.