PMID- 36911656
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230315
IS  - 2674-0826 (Electronic)
IS  - 2674-0826 (Linking)
VI  - 2
DP  - 2022
TI  - TLR4 signaling modulates extracellular matrix production in the lamina cribrosa.
LID - 968381 [pii]
LID - 10.3389/fopht.2022.968381 [doi]
AB  - The optic nerve head (ONH) is a place of vulnerability during glaucoma 
      progression due to increased intraocular pressure damaging the retinal ganglion 
      cell axons. The molecular signaling pathways involved in generating glaucomatous 
      ONH damage has not been fully elucidated. There is a great deal of evidence that 
      pro-fibrotic TGFbeta2 signaling is involved in modulating the ECM environment within 
      the lamina cribrosa (LC) region of the ONH. Here we investigated the role of 
      signaling crosstalk between the TGFbeta2 pathway and the toll-like receptor 4 (TLR4) 
      pathway within the LC. ECM deposition was examined between healthy and 
      glaucomatous human ONH sections, finding increases in fibronectin and fibronectin 
      extra domain A (FN-EDA) an isoform of fibronectin known to be a damage associated 
      molecular pattern (DAMP) that can activate TLR4 signaling. In human LC cell 
      cultures derived from healthy donor eyes, inhibition of TLR4 signaling blocked 
      TGFbeta2 induced FN and FN-EDA expression. Activation of TLR4 by cellular FN (cFN) 
      containing the EDA isoform increased both total FN production and Collagen-1 
      production and this effect was dependent on TLR4 signaling. These studies 
      identify TGFbeta2-TLR4 signaling crosstalk in LC cells of the ONH as a novel pathway 
      regulating ECM and DAMP production.
FAU - Geiduschek, Emma K
AU  - Geiduschek EK
AD  - Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, 
      Madison, WI, United States.
FAU - Milne, Paige D
AU  - Milne PD
AD  - Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, 
      Madison, WI, United States.
FAU - Mzyk, Philip
AU  - Mzyk P
AD  - Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, 
      Madison, WI, United States.
FAU - Mavlyutov, Timur A
AU  - Mavlyutov TA
AD  - Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, 
      Madison, WI, United States.
FAU - McDowell, Colleen M
AU  - McDowell CM
AD  - Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, 
      Madison, WI, United States.
LA  - eng
GR  - P30 EY016665/EY/NEI NIH HHS/United States
GR  - R01 EY026529/EY/NEI NIH HHS/United States
GR  - T32 EY027721/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20220819
PL  - Switzerland
TA  - Front Ophthalmol (Lausanne)
JT  - Frontiers in ophthalmology
JID - 9918419176106676
PMC - PMC9997209
MID - NIHMS1863116
OTO - NOTNLM
OT  - ECM - extracellular matrix
OT  - ONH
OT  - TGFbeta2
OT  - TLR4 - toll-like receptor 4
OT  - lamina cribrosa
COIS- Conflict of interest The authors declare that the research was conducted in the 
      absence of any commercial or financial relationships that could be construed as a 
      potential conflict of interest.
EDAT- 2022/01/01 00:00
MHDA- 2022/01/01 00:01
PMCR- 2023/03/09
CRDT- 2023/03/13 04:29
PHST- 2023/03/13 04:29 [entrez]
PHST- 2022/01/01 00:00 [pubmed]
PHST- 2022/01/01 00:01 [medline]
PHST- 2023/03/09 00:00 [pmc-release]
AID - 968381 [pii]
AID - 10.3389/fopht.2022.968381 [doi]
PST - ppublish
SO  - Front Ophthalmol (Lausanne). 2022;2:968381. doi: 10.3389/fopht.2022.968381. Epub 
      2022 Aug 19.