Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines
Ultraviolet light B (UVB)-irradiation is linked to various ocular pathologies such as limbal stem cell defects in pterygium. Despite the large circumstantial evidence linking UVB irradiation and limbal epithelial stem cell damage, the precise molecular responses of limbal stem cells to UVB irradiati...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-11-01
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| Series: | Stem Cell Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506115001439 |
| _version_ | 1818251802108231680 |
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| author | Maria Notara Refaian N. Braun G. Steven P. Bock F. Cursiefen C. |
| author_facet | Maria Notara Refaian N. Braun G. Steven P. Bock F. Cursiefen C. |
| author_sort | Maria Notara |
| collection | DOAJ |
| description | Ultraviolet light B (UVB)-irradiation is linked to various ocular pathologies such as limbal stem cell defects in pterygium. Despite the large circumstantial evidence linking UVB irradiation and limbal epithelial stem cell damage, the precise molecular responses of limbal stem cells to UVB irradiation are unclear. Here the effect of UVB irradiation on the putative stem cell phenotype, limbal niche cells and the subsequent effects on corneal (lymph)angiogenic privilege were investigated. Primary human limbal epithelial stem cells and fibroblasts were irradiated with 0.02 J/cm2 of UVB, a low dose corresponding to 3 min of solar irradiation. UVB irradiation caused significant reduction of limbal epithelial and limbal fibroblast proliferation for 24 h, but apoptosis of limbal epithelial stem cells only. Moreover, UVB induced stem-like character loss of limbal epithelial cells, as their colony forming efficiency and putative stem cell marker expression significantly decreased. Interestingly, limbal epithelial cells co-cultured with UVB-irradiated limbal fibroblasts also exhibited loss of stem cell character and decrease of colony forming efficiency. Conditioned media from limbal epithelial cells inhibited lymphatic endothelial cell proliferation and tube network complexity; however this effect diminished following UVB irradiation. In contrast, pro-inflammatory and macrophage-recruiting cytokines such as TNFα, IFNγ and MCP1 were significantly upregulated following cell irradiation of limbal fibroblasts. These data demonstrate the key role of the limbal stem cell niche in response to UVB and subsequent (lymph)angiogenic and inflammatory events. These data suggest that the known pro(lymph)angiogenic effect of UVB irradiation in pterygium is not linked to a direct up-regulation of pro-angiogenic cytokines, but rather to indirect macrophage-recruiting cytokines being upregulated after UVB irradiation. |
| first_indexed | 2024-12-12T16:14:04Z |
| format | Article |
| id | doaj.art-3a65b7ca62154a709769aae8e970a01a |
| institution | Directory Open Access Journal |
| issn | 1873-5061 1876-7753 |
| language | English |
| last_indexed | 2024-12-12T16:14:04Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-3a65b7ca62154a709769aae8e970a01a2022-12-22T00:19:08ZengElsevierStem Cell Research1873-50611876-77532015-11-0115364365410.1016/j.scr.2015.10.008Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokinesMaria NotaraRefaian N.Braun G.Steven P.Bock F.Cursiefen C.Ultraviolet light B (UVB)-irradiation is linked to various ocular pathologies such as limbal stem cell defects in pterygium. Despite the large circumstantial evidence linking UVB irradiation and limbal epithelial stem cell damage, the precise molecular responses of limbal stem cells to UVB irradiation are unclear. Here the effect of UVB irradiation on the putative stem cell phenotype, limbal niche cells and the subsequent effects on corneal (lymph)angiogenic privilege were investigated. Primary human limbal epithelial stem cells and fibroblasts were irradiated with 0.02 J/cm2 of UVB, a low dose corresponding to 3 min of solar irradiation. UVB irradiation caused significant reduction of limbal epithelial and limbal fibroblast proliferation for 24 h, but apoptosis of limbal epithelial stem cells only. Moreover, UVB induced stem-like character loss of limbal epithelial cells, as their colony forming efficiency and putative stem cell marker expression significantly decreased. Interestingly, limbal epithelial cells co-cultured with UVB-irradiated limbal fibroblasts also exhibited loss of stem cell character and decrease of colony forming efficiency. Conditioned media from limbal epithelial cells inhibited lymphatic endothelial cell proliferation and tube network complexity; however this effect diminished following UVB irradiation. In contrast, pro-inflammatory and macrophage-recruiting cytokines such as TNFα, IFNγ and MCP1 were significantly upregulated following cell irradiation of limbal fibroblasts. These data demonstrate the key role of the limbal stem cell niche in response to UVB and subsequent (lymph)angiogenic and inflammatory events. These data suggest that the known pro(lymph)angiogenic effect of UVB irradiation in pterygium is not linked to a direct up-regulation of pro-angiogenic cytokines, but rather to indirect macrophage-recruiting cytokines being upregulated after UVB irradiation.http://www.sciencedirect.com/science/article/pii/S1873506115001439Limbal stem cellsLimbal nicheUltraviolet B irradiationCorneal angiogenesisAngiogenesis proteinsPro-inflammatory cytokines |
| spellingShingle | Maria Notara Refaian N. Braun G. Steven P. Bock F. Cursiefen C. Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines Stem Cell Research Limbal stem cells Limbal niche Ultraviolet B irradiation Corneal angiogenesis Angiogenesis proteins Pro-inflammatory cytokines |
| title | Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines |
| title_full | Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines |
| title_fullStr | Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines |
| title_full_unstemmed | Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines |
| title_short | Short-term uvb-irradiation leads to putative limbal stem cell damage and niche cell-mediated upregulation of macrophage recruiting cytokines |
| title_sort | short term uvb irradiation leads to putative limbal stem cell damage and niche cell mediated upregulation of macrophage recruiting cytokines |
| topic | Limbal stem cells Limbal niche Ultraviolet B irradiation Corneal angiogenesis Angiogenesis proteins Pro-inflammatory cytokines |
| url | http://www.sciencedirect.com/science/article/pii/S1873506115001439 |
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