In vivo visualisation of murine corneal nerve fibre regeneration in response to ciliary neurotrophic factor

Reichard, Maria; Hovakimyan, Marina; Guthoff, Rudolf; Stachs, Oliver

doi:10.1016/j.exer.2013.12.015

Cited by 28 publications

(21 citation statements)

References 49 publications

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“…However, in our study the patients were young adults between 22-49 years of age. According to earlier studies, significant corneal nerve density reduction occurred at elderly ages mainly (70 years or older) (He et al 2010, Reichard et al 2014. This fact explains our results.…”

Section: Vol 67supporting

confidence: 83%

“…67 density, between diabetic patients and healthy individuals, within different corneal layers. Diabetic keratopathy has been shown to be associated with a thinner epithelium, decreased basal epithelial and endothelial cell density, and decreased density of keratocytes (Rosenberg et al 2000, Quadrado et al 2006, Szalai et al 2016, Dehghani et al 2016.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Diabetes Mellitus Type 1 Diagnosis on the Corneal Cell Densities and Nerve Fibers

Burdová

Kulich²,

Dotrelová³

et al. 2018

Physiol Res

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Relation of diabetes mellitus (DM) to the various stages of corneal nerve fiber damage is well accepted. A possible association between changes in the cornea of diabetic patients and diabetic retinopathy (DR), DM duration, and age at the time of DM diagnosis were evaluated. The study included 60 patients with DM type 1 (DM1) and 20 healthy control subjects. The density of basal epithelial cells, keratocytes and endothelial cells, and the status of the subbasal nerve fibers were evaluated using in vivo corneal confocal microscopy. Basal epithelial cell density increased with age (p=0.026), while stromal and endothelial cell density decreased with age (p=0.003, p=0.0005, p<0.0001).After the DM1 diagnosis was established, this association with age weaken. We showed nerve fiber damage in DM1 patients (p˂0.0001). The damage correlated with the degree of DR. DM1 patients with higher age at DM1 diagnosis had a higher nerve fiber density (p=0.0021). These results indicated that age at DM1 diagnosis potentially has an important effect on final nerve fiber and corneal cell density.

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Section: Vol 67supporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Effect of Diabetes Mellitus Type 1 Diagnosis on the Corneal Cell Densities and Nerve Fibers

Burdová

Kulich²,

Dotrelová³

et al. 2018

Physiol Res

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“…In cornea, CNTF was detected in corneal endothelium and pterygium fibroblasts . Recently, it was reported that local CNTF application accelerated the recovery of mouse corneal nerve fiber density . However, there was no definite conclusion about the role of CNTF in corneal epithelial stem cells and wound healing.…”

Section: Introductionmentioning

confidence: 99%

Ciliary Neurotrophic Factor Promotes the Activation of Corneal Epithelial Stem/Progenitor Cells and Accelerates Corneal Epithelial Wound Healing

Zhou

Chen

et al. 2015

Stem Cells

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Ciliary neurotrophic factor (CNTF), a well-known neuroprotective cytokine, has been found to play an important role in neurogenesis and functional regulations of neural stem cells. As one of the most innervated tissue, however, the role of CNTF in cornea epithelium remains unclear. This study was to explore the roles and mechanisms of CNTF in the activation of corneal epithelial stem/progenitor cells and wound healing of both normal and diabetic mouse corneal epithelium. In mice subjecting to mechanical removal of corneal epithelium, the corneal epithelial stem/progenitor cell activation and wound healing were promoted by exogenous CNTF application, while delayed by CNTF neutralizing antibody. In cultured corneal epithelial stem/progenitor cells, CNTF enhanced the colony-forming efficiency, stimulated the mitogenic proliferation, and upregulated the expression levels of corneal epithelial stem/progenitor cell-associated transcription factors. Furthermore, the promotion of CNTF on the corneal epithelial stem/progenitor cell activation and wound healing was mediated by the activation of STAT3. Moreover, in diabetic mice, the content of CNTF in corneal epithelium decreased significantly when compared with that of normal mice, and the supplement of CNTF promoted the diabetic corneal epithelial wound healing, accompanied with the advanced activation of corneal epithelial stem/progenitor cells and the regeneration of corneal nerve fibers. Thus, the capability of expanding corneal epithelial stem/progenitor cells and promoting corneal epithelial wound healing and nerve regeneration indicates the potential application of CNTF in ameliorating limbal stem cell deficiency and treating diabetic keratopathy. STEM CELLS 2015;33:1566-1576

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“…For instance, in vitro co-culture shows that trigeminal neurons release neurotransmitters and peptides to stimulate epithelial growth, proliferation, differentiation, and collagen production [112–114]. Corneal epithelial cells on the other hand secrete growth factors to promote neurite extension and survival, [115–117] including NGF [118], VEGF-a [119], CNTF [120, 121] and EGF [34]. Our recent study using a whole genome cDNA array revealed that while NGF, CNTF, VEGF-a, IL-6 (a neuropoietic cytokine) were all up-regulated in response to wounding in normoglycemia corneas, the upregulated expression of NGF, CNTF and IL-6 were significantly suppressed in diabetic rat corneal epithelial cells.…”

mentioning

confidence: 99%

“…Mice with wounded corneas treated with ciliary neurotropic factor (CNTF)-containing eye drops showed an increased nerve fiber density 8 weeks after wounding, as opposed to those receiving sham treatment. [121] Glial cell-derived neurotrophic factor (GDNF) was found to stimulate the migration of cultured human corneal epithelial cells. [151]…”

mentioning

confidence: 99%

Sensory nerve regeneration after epithelium wounding in normal and diabetic corneas

Yu¹,

Yin

Lee

et al. 2015

Expert Review of Ophthalmology

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Summary The cornea is the most densely innervated mammalian tissue. The sensory nerves are responsible for sensations of dryness, temperature, touch, and pain, and play important roles in the blink reflex, wound healing, and tear production. Many ocular and systemic diseases can adversely affect corneal sensory nerve and consequently impair their function. One of such systemic diseases is diabetes mellitus (DM) which causes sensory degeneration, neurotrophic keratopathy (DNK), and delayed wound healing. In this review, we summarize recent discoveries revealing mechanisms underlying the pathogenesis of DNK and the impairment of sensory nerve regeneration in post wound diabetic corneas in using animal model of human diabetes. Because it is generally believed that common mechanisms are operative in the pathogenesis of diabetic peripheral neuropathy in different tissues, the findings in the corneas have implications in in other tissues such as the skin, which often leads to foot ulceration and amputation in diabetic patients.

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In vivo visualisation of murine corneal nerve fibre regeneration in response to ciliary neurotrophic factor

Cited by 28 publications

References 49 publications

Effect of Diabetes Mellitus Type 1 Diagnosis on the Corneal Cell Densities and Nerve Fibers

Effect of Diabetes Mellitus Type 1 Diagnosis on the Corneal Cell Densities and Nerve Fibers

Ciliary Neurotrophic Factor Promotes the Activation of Corneal Epithelial Stem/Progenitor Cells and Accelerates Corneal Epithelial Wound Healing

Sensory nerve regeneration after epithelium wounding in normal and diabetic corneas

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