Systemic and Ocular Long Pentraxin 3 in Patients with Age-Related Macular Degeneration
(2015) In PLoS ONE 10(7). p.1-12- Abstract
Age-related macular degeneration (AMD) has been associated with both systemic and ocular alterations of the immune system. In particular dysfunction of complement factor H (CFH), a soluble regulator of the alternative pathway of the complement system, has been implicated in AMD pathogenesis. One of the ligands for CFH is long pentraxin 3 (PTX3), which is produced locally in the retinal pigment epithelium (RPE). To test the hypothesis that PTX3 is relevant to retinal immunohomeostasis and may be associated with AMD pathogenesis, we measured plasma PTX3 protein concentration and analyzed the RPE/choroid PTX3 gene expression in patients with AMD. To measure the ability of RPE cells to secrete PTX3 in vitro, polarized ARPE-19 cells were... (More)
Age-related macular degeneration (AMD) has been associated with both systemic and ocular alterations of the immune system. In particular dysfunction of complement factor H (CFH), a soluble regulator of the alternative pathway of the complement system, has been implicated in AMD pathogenesis. One of the ligands for CFH is long pentraxin 3 (PTX3), which is produced locally in the retinal pigment epithelium (RPE). To test the hypothesis that PTX3 is relevant to retinal immunohomeostasis and may be associated with AMD pathogenesis, we measured plasma PTX3 protein concentration and analyzed the RPE/choroid PTX3 gene expression in patients with AMD. To measure the ability of RPE cells to secrete PTX3 in vitro, polarized ARPE-19 cells were treated with activated T cells or cytokines (interferon (IFN)-gamma and/or tumor necrosis factor (TNF)-alpha) from the basolateral side; then PTX3 protein concentration in supernatants and PTX3 gene expression in tissue lysates were quantified. Plasma levels of PTX3 were generally low and did not significantly differ between patients and controls (P=0.307). No statistically significant difference was observed between dry and exudative AMD nor was there any correlation with hsCRP or CFH genotype. The gene expression of PTX3 increased in RPE/choroid with age (P=0.0098 macular; P=0.003 extramacular), but did not differ between aged controls and AMD patients. In vitro, ARPE-19 cells increased expression of the PTX3 gene as well PTX3 apical secretions after stimulation with TNF-alpha or activated T cells (P<0.01). These findings indicate that PTX3 expressed in the eye cannot be detected systemically and systemic PTX3 may have little or no impact on disease progression, but our findings do not exclude that locally produced PTX3 produced in the posterior segment of the eye may be part of the AMD immunopathogenesis.
(Less)
- author
- Juel, Helene Bæk ; Faber, Carsten ; Munthe-Fog, Lea ; Bastrup-Birk, Simone ; Reese-Petersen, Alexander Lynge ; Falk, Mads Krüger ; Singh, Amardeep LU ; Sørensen, Torben Lykke ; Garred, Peter and Nissen, Mogens Holst
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adult, Aged, Aged, 80 and over, C-Reactive Protein/genetics, Case-Control Studies, Choroid Plexus/metabolism, Coculture Techniques, Disease Progression, Female, Gene Expression, Humans, Macular Degeneration/blood, Male, Middle Aged, Retinal Pigment Epithelium/metabolism, Serum Amyloid P-Component/genetics
- in
- PLoS ONE
- volume
- 10
- issue
- 7
- article number
- e0132800
- pages
- 1 - 12
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:26176960
- scopus:84941274974
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0132800
- language
- English
- LU publication?
- no
- id
- c1cd1ca8-b1a3-4b2c-b7c1-17b97c78d859
- date added to LUP
- 2019-05-21 10:51:25
- date last changed
- 2024-03-19 08:41:46
@article{c1cd1ca8-b1a3-4b2c-b7c1-17b97c78d859,
abstract = {{<p>Age-related macular degeneration (AMD) has been associated with both systemic and ocular alterations of the immune system. In particular dysfunction of complement factor H (CFH), a soluble regulator of the alternative pathway of the complement system, has been implicated in AMD pathogenesis. One of the ligands for CFH is long pentraxin 3 (PTX3), which is produced locally in the retinal pigment epithelium (RPE). To test the hypothesis that PTX3 is relevant to retinal immunohomeostasis and may be associated with AMD pathogenesis, we measured plasma PTX3 protein concentration and analyzed the RPE/choroid PTX3 gene expression in patients with AMD. To measure the ability of RPE cells to secrete PTX3 in vitro, polarized ARPE-19 cells were treated with activated T cells or cytokines (interferon (IFN)-gamma and/or tumor necrosis factor (TNF)-alpha) from the basolateral side; then PTX3 protein concentration in supernatants and PTX3 gene expression in tissue lysates were quantified. Plasma levels of PTX3 were generally low and did not significantly differ between patients and controls (P=0.307). No statistically significant difference was observed between dry and exudative AMD nor was there any correlation with hsCRP or CFH genotype. The gene expression of PTX3 increased in RPE/choroid with age (P=0.0098 macular; P=0.003 extramacular), but did not differ between aged controls and AMD patients. In vitro, ARPE-19 cells increased expression of the PTX3 gene as well PTX3 apical secretions after stimulation with TNF-alpha or activated T cells (P<0.01). These findings indicate that PTX3 expressed in the eye cannot be detected systemically and systemic PTX3 may have little or no impact on disease progression, but our findings do not exclude that locally produced PTX3 produced in the posterior segment of the eye may be part of the AMD immunopathogenesis. </p>}},
author = {{Juel, Helene Bæk and Faber, Carsten and Munthe-Fog, Lea and Bastrup-Birk, Simone and Reese-Petersen, Alexander Lynge and Falk, Mads Krüger and Singh, Amardeep and Sørensen, Torben Lykke and Garred, Peter and Nissen, Mogens Holst}},
issn = {{1932-6203}},
keywords = {{Adult; Aged; Aged, 80 and over; C-Reactive Protein/genetics; Case-Control Studies; Choroid Plexus/metabolism; Coculture Techniques; Disease Progression; Female; Gene Expression; Humans; Macular Degeneration/blood; Male; Middle Aged; Retinal Pigment Epithelium/metabolism; Serum Amyloid P-Component/genetics}},
language = {{eng}},
number = {{7}},
pages = {{1--12}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Systemic and Ocular Long Pentraxin 3 in Patients with Age-Related Macular Degeneration}},
url = {{http://dx.doi.org/10.1371/journal.pone.0132800}},
doi = {{10.1371/journal.pone.0132800}},
volume = {{10}},
year = {{2015}},
}