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Yong-Soo Byun, Borami Kang, Young-Sik Yoo, Choun-Ki Joo; Poly(ADP-ribose) polymerase inhibition improves corneal epithelial innervation and wound healing in diabetic corneas. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3070.
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© ARVO (1962-2015); The Authors (2016-present)
We evaluated the effect of PARP inhibitor, 1,5-isoquinolinediol (ISO), on the alteration of corneal epithelial innervation in diabetes.
ISO (3mg/kg, intraperitoneal) or vehicle was administered to streptozotocin (STZ)-induced diabetic rats for 4 weeks. The epithelial innervation, epithelial wound healing, and corneal sensation were evaluated in diabetic rats treated vehicle (DM rats), diabetic rats treated with ISO (DM-ISO rats), and healthy non-diabetic (non-DM) rats. The density of epithelial innervation was calculated separately as nerve terminals and subbasal nerve plexus by analyzing the images of whole mount corneas stained with βⅢ-tubulin antibody. To compare the epithelial wound healing, the images of the epithelial defect were obtained at 0, 18, 36 h after creating a 4 mm wound on the cornea and the healed area of epithelial defect were measured. Corneal sensitivity test was conducted using a Cochet-Bonnet handheld esthesiometer. Additionally, PARP1 and poly(ADP-ribosyl)ated polymers (pADPr) as its products, were identified in trigeminal ganglions (TGs) by Western blot analysis and immunofluorescence staining.
In DM rats, the density of epithelial nerve terminals (5.57 ± 0.94%) and subbasal nerve plexus (22.08 ± 1.78 mm/mm2) was significantly reduced, as compared to DM-ISO rats (8.64 ± 1.42%, 30.82 ± 2.01 mm/mm2) or non-DM rats (9.02 ± 1.14%, 34.77 ± 4.45 mm/mm2). The healed area (%) of epithelial defect at 18, 36 h was significantly lower in DM rats (23.8 ± 5.2%, 53.2 ± 4.6%) than in DM-ISO rats (43.2 ± 1.4%, 75.8 ± 2.2%) or non-DM rats (48.1 ± 8.6%, 86.1 ± 3.3%). The corneal sensitivity was also decreased in DM rats, not in DM-ISO rats. There were no differences in all parameters between DM-ISO and non-DM rats. The abundance of pADPr was increased in the TGs of DM rats, whereas not in the TGs of DM-ISO or non-DM rats.
Diabetic corneas showed loss of epithelial innervation, along with delayed epithelial healing and decreased corneal sensitivity. PARP inhibition alleviated these diabetes induced alterations in corneal epithelium.
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