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xi han, XIAOMIN CHEN, Yang Liu, Wendy R Kam, David A Sullivan, Juan Ding; The effect of human growth hormone on corneal wound healing in mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):146.
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© ARVO (1962-2015); The Authors (2016-present)
We hypothesize that human growth hormone (HGH) promotes cornea wound healing by facilitating corneal epithelial migration and nerve regeneration. We have previously shown that HGH accelerated corneal epithelial cell migration and activated STAT5 signaling pathway in vitro. We also hypothesize that HGH increases re-innervation by inducing insulin-like growth factor (IGF)-1 expression in corneal epithelial cells and corneal fibroblasts.
Male wild type C57BL/6 mice of 3 months of age were subjected to 1.5mm central corneal epithelial debridement in both eyes, with one eye treated with HGH dissolved in carboxymethylcellulose (vehicle) and the fellow eye with vehicle. Corneal fluorescein imaging was taken at baseline, 4h, 8h, 12h, 18h, 24h and 48h post debridement to monitor re-epithelialization. Physiological (10 nM) and pharmacological (6.7 uM) doses of HGH were tested in separate experiments, with one drop instilled to the ocular surface three times a day throughout the study period. Mice were sacrificed at 48h time points; cornea whole mounts were stained with beta-3 tubulin antibody for confocal microscopy to detect corneal nerve regeneration. Human corneal epithelial cells (HCECs) and human corneal fibroblasts (HCFs) were treated with 10 nM HGH, and IGF-1 was assessed from whole cell lysates via Western Blot.
We have successfully established a mouse model of corneal epithelium debridement in vivo. We found that HGH of both doses were well-tolerated in these mice without adverse reactions. However, we found no significant difference in epithelial wound healing rate in HGH treated vs control eyes at any of the time points tested. Complete re-epithelialization was observed between 24 and 48 hours in both conditions. Our preliminary data did not show a significant increase in corneal nerve regeneration by HGH treatment. Further, we found that HCECs and HCFs did not produce detectable levels of IGF-1 with or without HGH treatment in vitro.
We have shown that HGH is well tolerated on the ocular surface in mice, but under the conditions tested, we did not find a significant effect of HGH on corneal epithelial healing or nerve regeneration, and it appeared that HGH did not stimulate IGF-1 production in human corneal cell lines in vitro. Dose- and time-dependent studies in females are needed before ruling out a positive effect of HGH on corneal wound healing in vivo.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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