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Hiroki Ueno, Takaaki Hattori, Yuta Kumagai, Noboru Suzuki, Satoki Ueno, Hitoshi Takagi; Alterations in the corneal nerve in type 2 diabetes: preventive effects of insulin-like growth factor-1 treatment. Invest. Ophthalmol. Vis. Sci. 2014;55(13):489. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic keratopathy (DK) remains difficult to be treated. It can cause corneal persistent epithelial defects, suggesting a role of corneal nerves in maintaining the corneal homeostasis. The purpose of this study is to investigate whether corneal nerve is altered in diabetic mice and examine whether the topical application of recombinant human insulin-like growth factor-I (rhIGF-I) normalized these alterations.
A group consisting of 12-week-old male mice (C57 BLKS db/db mice) with type 2 diabetes mellitus (DM) and a wild-type group were assessed by beta-III tubulin (neural marker) immunostaining. For rhIGF-1 treatment of the diabetic group, 11-week-old ob/ob mice were administered a retrobulbar injection of 100 μg/kg rhIGF-I twice daily for 7 days. On day 7 of the postexperimental procedure, the corneas from diabetic animals were similarly evaluated. In addition, the subbasal density of the corneal nerves was measured in all groups, including rhIGF-1-treated diabetic mice.
Beta-III tubulin expression detected with immunostaining was decreased in the diabetic corneas. Corneal subbasal plexus of nerve fibers with type II DM were preferentially thinner and had fewer branches compared to the normal mice. Compared with the subbasal nerve density in the normal group (58.29 ± 3.94 mm/mm2), a decrease in the diabetic group (27.01 ± 3.70 mm/mm2; P < 0.00001) was observed, whereas the corneal subbasal nerve density significantly increased in the rhIGF-1-treated diabetic group. (38.06 ± 1.67 mm/mm2; P < 0.01).
Our data suggest that corneal subbasal nerve is altered in db/db mice, and rhIGF-I treatment is capable of protecting against corneal damage in type 2 DM. Direct application of rhIGF-1 may serve as an useful strategy for treating severe type 2 DM.
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