Treatment failure in neovascular age-related macular degeneration is associated with a complex chemokine receptor profile.
degeneration
immunology
macula
neovascularisation
treatment medical
Journal
BMJ open ophthalmology
ISSN: 2397-3269
Titre abrégé: BMJ Open Ophthalmol
Pays: England
ID NLM: 101714806
Informations de publication
Date de publication:
2019
2019
Historique:
received:
18
03
2019
revised:
21
05
2019
accepted:
26
06
2019
entrez:
16
8
2019
pubmed:
16
8
2019
medline:
16
8
2019
Statut:
epublish
Résumé
To investigate if chemokine expression patterns on leucocyte subsets influence the short-term anatomical treatment response of intravitreal antivascular endothelial growth factor therapy against neovascular age-related macular degeneration (AMD). This study was conducted as a prospective observational cohort study of 79 patients with neovascular AMD. We used optical coherence tomography to quantify central retinal thickness (CRT) and to evaluate the presence of intraretinal and subretinal fluids in treatment-naive patients at baseline and after loading dose. Anatomical response was categorised into either good responders (complete regression of fluid or a reduction of >75% in CRT), partial responders (reduction of 0%-75% in CRT) or non-responders (increase of CRT). Expression levels of chemokine receptors (CCR1, CCR2, CCR3, CCR5, CXCR3 and CX3CR1) were measured on leucocyte subsets (monocytes, CD4 +T cells, and CD8 +T cells) using flow cytometry. Finally, we explored potential correlation patterns of chemokine expression between the leucocyte subsets using group-specific correlation networks. Non-responders had higher CCR1 expression on monocytes (p=0.016) and lower CCR3 expression on CD8+ T cells (p=0.037). Correlation network analyses of chemokine receptor expression patterns on leucocyte subsets revealed intergroup differences. Short-term anatomical treatment response in neovascular AMD varies according to the leucocyte subset chemokine expression pattern, which confirms that immune dysfunction is a complex issue in AMD. Our results suggest that focusing on chemokines may be a relevant approach towards personalised treatment in neovascular AMD.
Identifiants
pubmed: 31414053
doi: 10.1136/bmjophth-2019-000307
pii: bmjophth-2019-000307
pmc: PMC6668607
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e000307Déclaration de conflit d'intérêts
Competing interests: None.
Références
Ann Neurol. 2003 Nov;54(5):638-46
pubmed: 14595653
Cytometry A. 2007 Aug;71(8):632-6
pubmed: 17487891
J Clin Invest. 2007 Oct;117(10):2920-8
pubmed: 17909628
Arch Neurol. 2009 Feb;66(2):161-5
pubmed: 19064741
Nature. 2009 Jul 9;460(7252):225-30
pubmed: 19525930
J Neuroinflammation. 2010 Dec 02;7:87
pubmed: 21126357
Curr Eye Res. 2011 Mar;36(3):264-9
pubmed: 21275605
Br J Ophthalmol. 2012 May;96(5):752-6
pubmed: 22329913
Lancet. 2012 May 5;379(9827):1728-38
pubmed: 22559899
Invest Ophthalmol Vis Sci. 2012 Aug 07;53(9):5292-300
pubmed: 22789920
EMBO Mol Med. 2013 Nov;5(11):1775-93
pubmed: 24142887
Acta Ophthalmol. 2013 Nov;91 Thesis7:1-22
pubmed: 24206851
Clin Ophthalmol. 2014;8:15-21
pubmed: 24363550
BMC Ophthalmol. 2014 Feb 27;14:22
pubmed: 24575855
Invest Ophthalmol Vis Sci. 2014 May 08;55(7):4050-6
pubmed: 24812555
PLoS One. 2014 Dec 15;9(12):e112473
pubmed: 25503251
Eye (Lond). 2015 Jun;29(6):721-31
pubmed: 25882328
Ophthalmology. 2015 Sep;122(9):1837-45
pubmed: 26096346
Multivariate Behav Res. 1991 Jul 1;26(3):499-510
pubmed: 26776715
Cell Mol Life Sci. 2016 May;73(9):1765-86
pubmed: 26852158
Drug Des Devel Ther. 2016 Jun 02;10:1857-67
pubmed: 27330279
Dan Med J. 2016 Nov;63(11):
pubmed: 27808038
J Neuroinflammation. 2017 Feb 23;14(1):42
pubmed: 28231837
Sci Rep. 2017 Apr 4;7(1):605
pubmed: 28377586
Immun Ageing. 2017 Jul 27;14:18
pubmed: 28769990
Dan Med J. 2017 Nov;64(11):null
pubmed: 29115208
Clin Exp Ophthalmol. 2018 Aug;46(6):661-669
pubmed: 29360187
Ophthalmology. 2019 Jan;126(1):64-74
pubmed: 30149035