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Shintaro Nakao, Muneo Yamaguchi, Iori Wada, Yoshihiro Kaizu, Mitsuru Arima, Keijiro Ishikawa, Takahito Nakama, Wataru Shiraishi, Ryo Yamasaki, Junichi Kira, Tatsuro Ishibashi, Koh-hei Sonoda; Local Proliferation of CD206+ CX3CR1+ Macrophages at the Vitreoretinal Interface in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2682.
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© ARVO (1962-2015); The Authors (2016-present)
An increase in cellular components has been observed at the vitreoretinal interface in diabetic retinopathy (DR). In this study, we investigated the characteristics of macrophages at the diabetic vitreoretinal interface in diabetes patients and VEGF-overexpressing transgenic mice.
This prospective study included 155 eyes of 88 consecutive cases who visited Kyushu University Hospital. The presence of hyperreflective foci (HRF) at the vitreoretinal interface, reported as macrophages, was determined using en face OCT (Bi-μ, KOWA). The number of F4/80(+) macrophages at the vitreoretinal interface of diabetic Akita mice, VEGF-overexpressing Kimba and Akimba (Akita x Kimba), was examined with immunohistochemistry. Using Red (CCR2)-Green (CX3CR1) mice, or immunohistochemistry, the phenotypes were examined. To evaluate the local proliferation, BrdU was intraperitoneally administered to Kimba mice. Cultured bovine hyalocytes were stimulated in the vitreous in patients with DR or epiretinal membrane to estimate the proliferation.
Larger HRF at the vitreous interface could be observed significantly in the DR eye (128 eyes) compared to diabetes without DR (12 eyes) or non-diabetes (15 eyes) (P<0.01). In comparison with WT or Akita mice, macrophages increased significantly at the vitreoretinal interface of Kimba or Akimba mice (P<0.01). These expressed CD206 as well as CX3CR1. Incorporation of BrdU was observed at 50.4 ± 6.6% of these cells. DR vitreous significantly increased proliferative capacity compared to control (P<0.01).
In an environment with high VEGF such as DR, CD206+ CX3CR1+ macrophages increase at the vitreoretinal interface by local proliferation, possibly contributing to the pathogenesis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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