Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04
  • 2024-05

    • UV induced changes in the cornea are largely mediated by

    2018-11-08

    UV-induced changes in the cornea are largely mediated by the up-regulation of pro-inflammatory cytokines such as interleukin (IL)1 (Corsini et al., 1997), IL6 (Di Girolamo et al., 2002), IL8 (Di Girolamo et al., 2002) and tumour necrosis factor alpha (TNFα) (Kennedy et al., 1997) which correlate to the increased inflammatory cell infiltrate associated to the condition. Also increased are growth factors including vascular endothelial growth factor (VEGF) (Fukuhara et al., 2013; Lee et al., 2001), platelet derived growth factor (PDGF) (Kria et al., 1996), transforming growth factor beta (TGFβ) and matrix metalloproteinases (MMP) (Dushku et al., 2001; Di Girolamo et al., 2005; Li et al., 2001), especially MMP1. VEGFC, the master regulator of lymphangiogenesis (Cursiefen et al., 2006), and its receptor VEGFR3 are also up-regulated in pterygium specimen (Fukuhara et al., 2013). This increase correlates to the higher density of lymphatic network associated with pterygium recurrence and staging (Ling et al., 2012a; Ling et al., 2012b). In this current study, we use an in vitro approach to explain the effect of UVB in the phenotype and functionality of human limbal epithelial purchase BTL105 and their accessory limbal fibroblasts as well as their paracrine signaling regulating inflammation and (lymph)angiogenesis.
    Materials and methods:
    Results
    Discussion: Corneal homeostasis is maintained as a result of an elegant and dynamic balance where the epithelium and its residing LESC population play a central role. Corneal injury or disease can cause a disruption of LESC function leading to epithelial breakdown and pathologic corneal neovascularization. In the normally avascular cornea, several anti-hem- and anti-lymphangiogenic strategies are expressed (Cursiefen et al., 2006; Bock et al., 2013). A shift in this balance may occur due to various forms of damage including burns, inflammation, infection or neoplasia. The elucidation of the mechanisms involved when this equilibrium is lost may help towards developing more efficient, better targeted treatments for these conditions. Here we aimed to understand the molecular events involved in disruption of cornea homeostasis as a result of UVB irradiation. Although sun exposure is essential for human health as it aids vitamin D synthesis, extensive exposure, is connected to chronic skin inflammation, skin ageing and melanoma (Reichrath & Reichrath, 2014). UVB-related ocular pathologies include cataract, conjunctival melanoma, macular degeneration (Roberts, 2011; Yam & Kwok, 2014; Sui et al., 2013) and of course pterygium, a benign tumor of the conjunctiva characterized by neovascularization, pain, inflammation and vision loss (Sul et al., 2014). Changes in the histology of the basal epithelium of pterygium samples indicate that damage of the limbal stem cell compartment may be critical for the disease onset. These cells start secretion of extracellular matrix remodeling molecules which aid cell invasion and matrix modification linked with the condition (Chui et al., 2011; Dushku et al., 2001). Here, the direct effects of UVB irradiation on limbal epithelial cells and fibroblasts as well as their subsequent contribution to a pro(lymph)angiogenic and pro-inflammatory milieu usually linked to pterygium were evaluated. To better understand the effects of the UVB to the limbal niche, we examined both cultured HLE and HLF. HLF are essential components of the niche microenvironment as they support the stem cells by producing suitable extracellular matrix and by providing the paracrine signaling cues that are necessary for them to maintain their phenotype and remain in quiescent state (Notara et al., 2010b). For the HLF to be able to provide their supporting role, a physical proximity with the LESCs is necessary. The cell-cell contact is facilitating the communication efficiency of the two populations (Dziasko et al., 2014). From the apoptosis assessment it became obvious that the epithelial cells were more susceptible to UVB irradiation compared to the fibroblasts as irradiated limbal stem cells showed a higher percentage of dead and apoptotic cells compared to limbal fibroblasts. UVB has been reported to induce apoptosis to both HLE and HLF (Tong et al., 2006; Xing et al., 2006) although under the current experimental conditions this was observed only in irradiated limbal epithelial cells. Following irradiation and 24h after plating, both limbal niche cell types exhibited a reduced metabolic activity while still recovering from the UVB insult. However, at 48h post plating, the alamar blue reduction values for both cell types reached their control level again. Therefore, 48h post plating was selected as the time-point that conditioned media was collected for analysis and to use in the experiments involving paracrine effect on LEC and BEC cells.