June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Poly(ADP-ribose) polymerase inhibition improves corneal epithelial innervation and wound healing in diabetic corneas
Author Affiliations & Notes
  • Yong-Soo Byun
    Ophthalmology and Visual Science, Catholic University of Korea, College of Medicine, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
    Catholic Institute for Visual Science, Seoul, Korea (the Republic of)
  • Borami Kang
    Division of Endocrinology and Metabolism, Department of Internal Medicine, Catholic University of Korea, College of Medicine, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
  • Young-Sik Yoo
    Ophthalmology and Visual Science, Catholic University of Korea, College of Medicine, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
    Catholic Institute for Visual Science, Seoul, Korea (the Republic of)
  • Choun-Ki Joo
    Ophthalmology and Visual Science, Catholic University of Korea, College of Medicine, Seoul St. Mary's Hospital, Seoul, Korea (the Republic of)
    Catholic Institute for Visual Science, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships Yong-Soo Byun, None; Borami Kang, None; Young-Sik Yoo, None; Choun-Ki Joo, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3070. doi:
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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)

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Abstract

Purpose: We evaluated the effect of PARP inhibitor, 1,5-isoquinolinediol (ISO), on the alteration of corneal epithelial innervation in diabetes.

Methods: 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.

Results: 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.

Conclusions: 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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