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A. Aracil, C.L. Luna, A. García-Valentín, C. Belmonte, J. Gallar; Impaired Corneal Epithelial Wound Healing in Mice Lacking the Genes for the Sensory Neuropeptides alpha-CGRP and Preprotachykinin A . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3272.
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Purpose:To study the role of alpha-CGRP and preprotachykinin-A (PPT-A) gene products in the corneal epithelial wound healing. Methods: 2 mm of diameter chemical wounds were performed in the corneal epithelium of mice with a targeted deletion of the alpha-CGRP (Salmon, AM, et al, 1998) or PPT-A (Zimmer, A, et al, 1998) genes and in the corresponding wild-type animals. The diameter of the epithelial wound was measured in a masked fashion every 12 hr by staining the ocular surface with fluorescein. A double-masked vehicle-controlled assay was performed to study the effect on wound healing of the application every 3 h of 500 pg/mL alpha-CGRP on alpha-CGRP and WT corneas. The Epithelial Migration Rate (EMR) and the Estimated Time of Healing (ETH) were calculated (Gallar et al, 1990). Results were compared with the t-test. Results: The EMR for the alpha-CGRP KO and their WT was respectively 4.7±1.6 and 32.8±7.7 µm/h (p<0.01, n=7), and for the PPT-A KO and their WT, 11.4±4.1 (n=6) and 32.1±2.1 (n=5) µm/h respectively (p<0.01). The ETH was longer in the KO mice than in the corresponding WT animals: 230.6±61.8 vs. 56.7±10.4 h (alpha-CGRP, p<0.01), 141.8±31.9 vs. 39.3±4.0 h (PPT-A, p<0.01). Exogenous application of alpha-CGRP delayed the healing in WT animals in comparison with mice treated with the vehicle (EMR: 13.16±2.14 vs. 29.8±2.63 µm/h, respectively, p=0.001), and failed to accelerate the healing in alpha-CGRP KO corneas (9.36±1.04 vs 19.92±5.33 µm/h, CGRP-treated vs. control, respectively). The exogenous peptide also produced corneal opacification of similar value in alpha-CGRP and WT mice. Conclusions: Alpha-CGRP and PPT-A genes products seem to play a role in the modulation of corneal epithelial wound healing. Supported by SAF99-C01-02 and -01. AA is a fellow from Generalitat Valenciana, Spain; CL from Fundación UPSA, Spain, and AGV from Ministerio de Educación y Cultura, Spain. Alpha-CGRP and PPT-A KO mice were constructed and kindly provided respectively by Drs. A-M Salmon and Dr. J.P. Changeux (Institut Pasteur, France), and Dr. A. Zimmer (University of Bonn, Germany).
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