Human growth hormone (HGH) activates epithelial cell movement in vivo, reports a new study published in the June 2015 Cornea.1 These findings could lead to topical compounds that promote more efficient corneal wound healing in patients with persistent corneal epithelial defects (PCEDs) by activating corneal epithelial cell proliferation and migration.
Researchers from Harvard Medical School and the University of Utah evaluated the effects of HGH cell signaling, proliferation and migration and whether insulin-like growth factor-1 (IGF-1) may mediate these effects using immortalized human corneal epithelial cells and primary human corneal fibroblasts. Five cultures were set up: corneal epithelial cells in keratinocyte serum-free medium (KSFM) supplemented with 5ng/mL epidermal growth factor (EGF) and 50μg/mL bovine pituitary extract (BPE) for two days; two cultures of corneal fibroblasts in 10% fetal bovine serum (FBS) for two days; and two cultures of corneal epithelial cells in 10% FBS for five to seven days.
After culturing, researchers withdrew the respective serum or supplement. Culture one was treated with HGH of increasing doses for 15 minutes, followed by cell lysis and immunoblotting. Cultures two through five were treated with either HGH or IGF-1 for 15 minutes. Researchers observed a dose-dependent increase of p-STAT5, a protein responsible for cell signaling, in both cell types. IGF-1 did not play a differentiating role.
In the second part of the study, researchers performed an in vitro scratch test on confluent epithelial cells cultured alone and together with fibroblasts, finding that HGH significantly increased corneal epithelial cell migration only in the epithelial cell/fibroblast combination cultures. “This indicates the HGH does not act on corneal epithelial cells directly to stimulate migration, but rather acts through an intact epithelial/fibroblast communication system. This duplicates the situation in vivo, where epithelia and stromal keratocytes coexist,” the researchers explain. IGF-1 did not play a significant role in cell migration.
A highly regulated process, corneal wound healing can be drastically impaired by ocular surface disease or trauma, systemic disease or surgical intervention.1 In some cases, this can lead to the development of PCEDs, which ultimately affect visual clarity. Treatment methods include patching, lubricants, ointments and even surgery, but currently no approved pharmacotherapy exists.1 Results from this study indicate, however, that HGH could be a potential topical therapeutic to promote corneal epithelial wound healing, suggesting further research is needed.
1. Ding J, Wirostko B, Sullivan DA. Human growth hormone promotes corneal epithelial cell migration in vitro. Cornea 2015 Jun;34(6):686-92.