| First Author | Levin MH | Year | 2006 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 47 |
| Issue | 10 | Pages | 4365-72 |
| PubMed ID | 17003427 | Mgi Jnum | J:116261 |
| Mgi Id | MGI:3693400 | Doi | 10.1167/iovs.06-0335 |
| Citation | Levin MH, et al. (2006) Aquaporin-3-dependent cell migration and proliferation during corneal re-epithelialization. Invest Ophthalmol Vis Sci 47(10):4365-72 |
| abstractText | PURPOSE: To determine a role for the water- and glycerol-transporting protein aquaporin-3 (AQP3) in mammalian corneal epithelium, where it is expressed but has no known function. METHODS: Corneal epithelial water and glycerol permeabilities were measured in living wild-type and AQP3-null mice using calcein fluorescence-quenching and 14C-glycerol-uptake assays, respectively. After removal of the corneal epithelium by scraping, re-epithelialization was followed by fluorescein staining. The contribution of AQP3-facilitated cell migration to corneal re-epithelialization was assessed using an organ culture model, in which initial resurfacing results from epithelial cell migration, as shown by BrdU analysis and 5-fluorouracil insensitivity, and by scratch wound assay using primary cultures of corneal epithelial cells from wild-type versus AQP3-null mice. Involvement of AQP3 in epithelial cell proliferation was investigated by morphometric and BrdU analysis of histologic sections, and by measurement of [3H]thymidine uptake in primary cultures of corneal epithelial cells. RESULTS: AQP3 deficiency did not alter corneal epithelial thickness, morphology, or glycerol content, though both water and glycerol permeabilities were reduced. Time to corneal re-epithelialization in vivo was significantly delayed in AQP3-null mice compared to wild-type mice. Delays were also found in organ and primary cultures, demonstrating a distinct defect in cell migration arising from AQP3 deletion. Delayed restoration of full-thickness epithelia of AQP3-null mice over days after scraping suggested a separate defect in epithelial cell proliferation, which was confirmed by reduction in proliferating BrdU-positive cells in AQP3-deficient mice during healing, and by reduced proliferation in primary cultures of corneal epithelial cells from AQP3-null mice. CONCLUSIONS: The significant impairment in corneal re-epithelialization in AQP3-deficient mice results from distinct defects in corneal epithelial cell migration and proliferation. The results provide evidence for involvement of an aquaporin in cell proliferation and suggest AQP3 induction as a possible therapy to accelerate the resurfacing of corneal defects. |
