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Matthew Petroll, Pouriska Kivanany; Modulation of corneal wound healing in the mouse using pre-surgical fasting. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1289.
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© 2017 Association for Research in Vision and Ophthalmology.
Long-term dietary restriction (DR), defined as reduced food intake without malnutrition, has been shown to extend lifespan in rodents, as well as provide increased resistance to many forms of acute stress. Long-term DR has also been shown to alter proliferation and fibrosis during dermal wound healing. Increased longevity has been shown to require long-term DR. However, recent studies have established that short-term, water only fasting is sufficient to promote many stress resistance responses. In this study, we investigate the effect of short-term fasting on corneal wound healing in the mouse.
A transcorneal freeze injury (FI) model was used on ten C57/BL6 mice. Animals were either fed ad libitum (5 mice) or underwent 2 days of water only fasting (5 mice) prior to receiving a 1 mm diameter FI in the center of the left eye. After FI, all mice were fed ad libitum. Wound healing was assessed from 3 to 28 days after injury using 3-D in vivo confocal microscopy with a custom modified HRT-Rostock Corneal Module. At 7 days, a subset of corneas was fixed in situ, labeled for f-actin and nuclei, and imaged using confocal fluorescence microscopy.
The epithelium was resurfaced at 3 days after FI in both fasted and non-fasted animals. In animals fed ad libitum, activated stromal cells were observed in the anterior stroma 3 days after FI. By 7 days, activated cells were present throughout the full thickness of the corneal stroma. Short-term fasting inhibited the initial wound healing response, as indicated by a lack of activated stromal cells 3 days after injury. At 7 days, stromal cell activation appeared similar between fasted and non-fasted animals. F-actin labeling confirmed that stromal cells expressed intracellular stress fibers at 7 days after FI in both fasted and non-fasted animals. Stromal cell activation was reduced at 14 and 21 days after injury in both fasted and non-fasted animals.
These initial results suggest that short term fasting reduces and/or delays the initial corneal stromal wound healing response in the mouse. We hypothesize that the transient nature of this response is due to the fact that the mice were refed at the time of injury. We hypothesize that by using DR both before and after injury, a sustained impact on wound healing could be achieved.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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