Expression of Neurotrophic Factors and their Receptors in Keratoconic Cornea

Chung, Eun‐Sung; Lee, Kwang Hyun; Kim, Min; Chang, Eunmi; Chung, Tae Young; Kim, Eung Kweon

doi:10.3109/02713683.2013.774421

Cited by 16 publications

(9 citation statements)

References 24 publications

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“…30 In the cornea, previous studies have found the patterned expression of neurotrophic factors and their receptors in normal and injured conditions. 11,15,16,31,32 In addition, our results revealed that GDNF receptor a 1, the main receptor of GDNF, was expressed in mouse and human corneal epithelium ( Supplementary Fig. S3).…”

Section: Discussionmentioning

confidence: 68%

Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration

Zhao

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 68%

Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration

Zhao

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…CNTF is one of the neurotrophic factors that have been found in diseased corneas 18 19 . Neurotrophic factors are a family of polypeptides with similar function in protecting the survival of the neurons, mainly including neurotrophins, glial cell-line derived neurotrophic factor family ligands (GFLs), and neuropoietic cytokines 20 .…”

Section: Discussionmentioning

confidence: 99%

“…The expression of CNTF has not been detected in normal human cornea by immunofluorescence 16 . However, it has been shown to be elevated in oxidative stressed corneal endothelium 17 , and in diseases such as in pterygeal tissues 18 and keratoconus (KC) cornea 19 . Even so, CNTF expression in the cornea after injury has yet not been reported, and it is furthermore unknown whether CNTF promotes the migration of corneal epithelial stem/progenitor cells during the repair process.…”

mentioning

confidence: 99%

Ciliary Neurotrophic Factor Promotes the Migration of Corneal Epithelial Stem/progenitor Cells by Up-regulation of MMPs through the Phosphorylation of Akt

Chen

Backman

et al. 2016

Sci Rep

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The migration of limbal epithelial stem cells is important for the homeostasis and regeneration of corneal epithelium. Ciliary neurotrophic factor (CNTF) has been found to promote corneal epithelial wound healing by activating corneal epithelial stem/progenitor cells. However, the possible effect of CNTF on the migration of corneal epithelial stem/progenitor cells is not clear. This study found the expression of CNTF in mouse corneal epithelial stem/progenitor cells (TKE2) to be up-regulated after injury, on both gene and protein level. CNTF promoted migration of TKE2 in a dose-dependent manner and the peak was seen at 10 ng/ml. The phosphorylation level of Akt (p-Akt), and the expression of MMP3 and MMP14, were up-regulated after CNTF treatment both in vitro and in vivo. Akt and MMP3 inhibitor treatment delayed the migration effect by CNTF. Finally, a decreased expression of MMP3 and MMP14 was observed when Akt inhibitor was applied both in vitro and in vivo. This study provides new insights into the role of CNTF on the migration of corneal epithelial stem/progenitor cells and its inherent mechanism of Up-regulation of matrix metalloproteinases through the Akt signalling pathway.

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“…3,5,9,39,40 In the cornea, previous studies have found the patterned expression of neurotrophic factors and their receptors in normal and injured conditions. [41][42][43][44] Although their exact roles in the maintenance of proper corneal innervations remain unclear, the decreased content of NGF, PEDF, and CNTF in the cornea may be one of the important factors in the degeneration of corneal nerve fibers following subconjunctival bevacizumab injection. In addition, previous research has reported that soluble VEGFR1 in the cornea sequesters the potent pro-angiogenic molecule VEGF-A, which is also contained in the avascular corneal tissue.…”

Section: Discussionmentioning

confidence: 99%

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

Dong

Zhang

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Dong M, Di G, Zhang X, Zhou Q, Shi W. Subconjunctival bevacizumab injection impairs corneal innervations and epithelial wound healing in mice. Invest Ophthalmol Vis Sci. 2017;58:146958: -147758: . DOI: 10.1167 PURPOSE. To investigate the effects of subconjunctival bevacizumab injection on the corneal nerve, sensitivity, and epithelial wound healing in mice.METHODS. Adult C57BL/6 mice were treated with subconjunctival injection of 1, 2, 5, or 25 mg/mL bevacizumab. The corneal nerve was observed with whole-mount anti-b3-tubulin fluorescence staining. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer. The protein levels of pigment epithelium-derived factor (PEDF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and ciliary neurotrophic factor (CNTF) were measured by ELISA. The corneal epithelial wound-healing rate was evaluated by fluorescein staining. The recovery of impaired mouse corneal innervations and epithelial wound-healing rate following bevacizumab injection was evaluated with the co-injection of PEDF, NGF, or CNTF.RESULTS. Subconjunctival bevacizumab injection caused apparent corneal nerve degeneration, attenuated corneal sensitivity, and delayed corneal epithelial wound healing and nerve regeneration in normal mice, which was more significant with increased concentration and times of the bevacizumab injection. However, the corneal nerve and sensitivity gradually improved and recovered in mice with a single injection of 1 to 5 mg/mL bevacizumab. Moreover, the bevacizumab injection significantly decreased the corneal PEDF, NGF, and CNTF content, whereas exogenous PEDF, NGF, or CNTF supplement attenuated impairment of the corneal nerve, sensitivity, and epithelial wound healing after subconjunctival bevacizumab injection.CONCLUSIONS. Subconjunctival bevacizumab injection impairs corneal innervations, epithelial wound healing, and nerve regeneration in normal mice, which may be caused by the reduction of neurotrophic factor content in the cornea.

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Expression of Neurotrophic Factors and their Receptors in Keratoconic Cornea

Abstract: The change in expression of neurotrophic factors in KC may suggest that these factors play an important role in the pathogenesis of KC and serve as new markers for the progression of KC.

Cited by 16 publications

References 24 publications

Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration

Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration

Ciliary Neurotrophic Factor Promotes the Migration of Corneal Epithelial Stem/progenitor Cells by Up-regulation of MMPs through the Phosphorylation of Akt

Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice

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