PMID- 31157834
OWN - NLM
STAT- MEDLINE
DCOM- 20191206
LR  - 20200309
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 60
IP  - 7
DP  - 2019 Jun 3
TI  - Remodeling of Substance P Sensory Nerves and Transient Receptor Potential 
      Melastatin 8 (TRPM8) Cold Receptors After Corneal Experimental Surgery.
PG  - 2449-2460
LID - 10.1167/iovs.18-26384 [doi]
AB  - PURPOSE: To investigate changes in corneal nerves positive to substance P (SP) 
      and transient receptor potential melastatin 8 (TRPM8) and gene expression in the 
      trigeminal ganglia (TG) following corneal surgery to unveil peripheral nerve 
      mechanism of induced dry eye-like pain (DELP). METHODS: Surgery was performed on 
      mice by removing the central epithelial and anterior stromal nerves. Mice were 
      euthanized at different times up to 15 weeks. Immunostaining was performed with 
      TRPM8, SP, or protein gene product 9.5 (PGP9.5) antibodies, and epithelial nerve 
      densities were calculated. The origin of TRPM8- and SP-TG neurons were analyzed 
      by retrograde tracing. Gene expression in TG was studied by real-time PCR 
      analysis. RESULTS: SP-positive epithelial corneal nerves were more abundant than 
      TRPM8 and were expressed in different TG neurons. After injury, epithelial nerve 
      regeneration occurs in two distinct stages. An early regeneration of the 
      remaining epithelial bundles reached the highest density on day 3 and then 
      rapidly degraded. From day 5, the epithelial nerves originated from the 
      underlying stromal nerves were still lower than normal levels by week 15. The SP- 
      and TRPM8-positive nerve fibers followed the same pattern as the total nerves. 
      TRPM8-positive terminals increased slowly and reached only half of normal values 
      by 3 months. Corneal sensitivity gradually increased and reached normal values on 
      day 12. Corneal injury also induced significant changes in TG gene expression, 
      decreasing trpm8 and tac1 genes. CONCLUSIONS: Abnormal SP expression, low amounts 
      of TRPM8 terminals, and hypersensitive nerve response occur long after the injury 
      and changes in gene expression in the TG suggest a contribution to the 
      pathogenesis of corneal surgery-induced DELP.
FAU - He, Jiucheng
AU  - He J
AD  - Neuroscience Center of Excellence, School of Medicine, Louisiana State University 
      Health New Orleans, New Orleans, Louisiana, United States.
AD  - Department of Ophthalmology, School of Medicine, Louisiana State University 
      Health New Orleans, New Orleans, Louisiana, United States.
FAU - Pham, Thang Luong
AU  - Pham TL
AD  - Neuroscience Center of Excellence, School of Medicine, Louisiana State University 
      Health New Orleans, New Orleans, Louisiana, United States.
FAU - Kakazu, Azucena H
AU  - Kakazu AH
AD  - Neuroscience Center of Excellence, School of Medicine, Louisiana State University 
      Health New Orleans, New Orleans, Louisiana, United States.
FAU - Bazan, Haydee E P
AU  - Bazan HEP
AD  - Neuroscience Center of Excellence, School of Medicine, Louisiana State University 
      Health New Orleans, New Orleans, Louisiana, United States.
AD  - Department of Ophthalmology, School of Medicine, Louisiana State University 
      Health New Orleans, New Orleans, Louisiana, United States.
LA  - eng
GR  - R01 EY019465/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (TRPM Cation Channels)
RN  - 0 (TRPM8 protein, mouse)
RN  - 33507-63-0 (Substance P)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - EC 3.4.19.12 (Uchl1 protein, mouse)
SB  - IM
EIN - Invest Ophthalmol Vis Sci. 2019 Jul 1;60(8):2860. PMID: 31260036
MH  - Animals
MH  - Cold Temperature
MH  - Corneal Injuries/*metabolism
MH  - Epithelium, Corneal/*innervation
MH  - Female
MH  - Fluorescent Antibody Technique, Indirect
MH  - Gene Expression Regulation/*physiology
MH  - Male
MH  - Mice
MH  - Models, Animal
MH  - Nerve Regeneration/physiology
MH  - Neuronal Plasticity/*physiology
MH  - Ophthalmic Nerve/*physiology
MH  - Real-Time Polymerase Chain Reaction
MH  - Substance P/*genetics/metabolism
MH  - TRPM Cation Channels/*genetics/metabolism
MH  - Tears/physiology
MH  - Ubiquitin Thiolesterase/genetics/metabolism
PMC - PMC6545819
EDAT- 2019/06/04 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/06/01
CRDT- 2019/06/04 06:00
PHST- 2019/06/04 06:00 [entrez]
PHST- 2019/06/04 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/06/01 00:00 [pmc-release]
AID - 2735524 [pii]
AID - IOVS-18-26384R2 [pii]
AID - 10.1167/iovs.18-26384 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2019 Jun 3;60(7):2449-2460. doi: 
      10.1167/iovs.18-26384.