June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Retinal leukostasis in diabetic mice immunized with Keyhole Limpet Hemocyanin
Author Affiliations & Notes
  • Manzo Taguchi
    Ophthalmology, National Defense Medical College, Tokorozawa, Japan
  • Makoto Inada
    Ophthalmology, National Defense Medical College, Tokorozawa, Japan
  • Toshihiko Murata
    Ophthalmology, National Defense Medical College, Tokorozawa, Japan
  • Kozo Harimoto
    Ophthalmology, National Defense Medical College, Tokorozawa, Japan
  • Yoko Karasawa
    Ophthalmology, National Defense Medical College, Tokorozawa, Japan
  • Masataka Ito
    Developmental Anatomy, National Defense Medical College, Tokorozawa, Japan
  • Masaru Takeuchi
    Ophthalmology, National Defense Medical College, Tokorozawa, Japan
  • Footnotes
    Commercial Relationships   Manzo Taguchi, None; Makoto Inada, None; Toshihiko Murata, None; Kozo Harimoto, None; Yoko Karasawa, None; Masataka Ito, None; Masaru Takeuchi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5735. doi:
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    • Get Citation

      Manzo Taguchi, Makoto Inada, Toshihiko Murata, Kozo Harimoto, Yoko Karasawa, Masataka Ito, Masaru Takeuchi; Retinal leukostasis in diabetic mice immunized with Keyhole Limpet Hemocyanin. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5735.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Akita mouse, which has a point mutation in exon3 of insulin 2 gene, is a non-obese type 1 diabetes (DM) model animal. Mice heterozygous of this mutant show development of hyperglycemia and hypo-insulinemia that are detectable after 4 weeks of age. However, no significant diabetic retinopathy (DMR) occurs. In both human and experimental animals, DM causes adhesion of leukocytes to vascular endothelial cells. We have recently indicated that T helper type 2 (Th2)- and Th17-related cytokines are elevated in the vitreous of proliferative diabetic retinopathy (PDR) patients. Keyhole Limpet Hemocyanin (KLH) originally isolated from the mollusc Megathura crenulata is a copper-containing protein found in the hemolymph of many arthropods and mollusca. It has been reported that, in mammals immunized by KLH, more Th cells differentiate into Th2 and Th17 cells. In this study, we evaluated retinal leukostasis, as an early sign of DMR, in Akita mouse immunized by KLH.

Methods : Six-week-old male Akita mice were injected subcutaneously with 50 µg of KLH (immunized group). Control group of Akita mice were injected with the same amounts of vehicle subcutaneously. Two weeks later, fundus observations and Spectral-Domain (SD) -OCT images were evaluated, followed by analysis of leukostasis in the retinal blood vessels using Con A-conjugated FITC perfusion.

Results : Ophthalmoscopic observations showed no retinal lesion characteristic of DMR, and no abnormal retinal structure was observed in SD-OCT. However, the leukostasis was increased in immunized group compared with control group with statistical significance (12.2 ± 1.4 / retina in the immunized group vs. 9.4 ± 1 / retina in the control group, P = 0.0101).

Conclusions : In the retinas of Akita mice immunized by KLH, mild inflammatory changes were observed, suggesting that Th17-related cytokines are involved in the etiology of DMR.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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