Journal of Applied Physiology AJP: Regulatory, Integrative and Comparative Physiology
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J Appl Physiol (April 2, 2004). doi:10.1152/japplphysiol.00200.2004
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Submitted on February 23, 2004
Accepted on March 31, 2004

Hind Limb Unloading Depresses Corneal Epithelial Wound Healing in Mice

Zhijie Li1, Chantal A Rivera1, Alan R Burns1, and C Wayne Smith1*

1 Section of Leukocyte Biology, Departments of Pediatrics, Medicine and Immunology, Baylor College of Medicine, Houston, Texas, USA

* To whom correspondence should be addressed. E-mail: cwsmith{at}bcm.tmc.edu.

C57Bl/6 mice were subjected to hindlimb unloading (HU) for a period of three weeks to determine the possible effects on epithelial wound healing. A standardized corneal epithelial wound was performed and parameters of the inflammatory response and re-epithelialization were analyzed over an observation period of 96 hours. Wound closure was significantly retarded in mice during HU with re-epithelialization being delayed by approximately 12 hours. Both epithelial migration and cell division were significantly depressed and delayed. The inflammatory response to epithelial wounding was also significantly altered during HU. Neutrophils as detected by the Gr-1 marker were initially elevated above normal levels prior to wounding and during the first few hours afterwards, but there was a significant reduction in neutrophil response to wounding at times where neutrophil influx and migration in controls were vigorous. A similar pattern was seen with CD11b+CD11c+ cells (monocyte lineage). Langerhans cells (LC) are normally resident within the peripheral corneal epithelium. They respond to injury by initially leaving the epithelial site within 6 hours and returning to normal levels by 96 hours, 2 days after re-epithelialization is complete. During HU this pattern is distinctly different, with LC numbers slowing diminishing, reaching a nadir at 96 hours, significantly below normal. Evidence for systemic effects of HU is provided by findings that collagen deposition within subcutaneous sponges was significantly reduced during HU. In conclusion, hind limb unloading, a ground-based model simulating some physiologic aspects of space flight, impairs wound repair of corneas. Multiple factors both local and systemic likely contribute to this delayed wound healing.




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