TY - JOUR
T1 - Diverse roles of macrophages in intraocular neovascular diseases
T2 - A review
AU - Zhou, Ye Di
AU - Yoshida, Shigeo
AU - Peng, Ying Qian
AU - Kobayashi, Yoshiyuki
AU - Zhang, Lu Si
AU - Tang, Luo Sheng
N1 - Funding Information:
that cytokines are involved in the pathogenesis, in recruitment of monocytes and polarization of macrophages, as well as in the effect of angiogenesis (Figure 2)[62]. High levels of IL-12, IL-18 and IL-23, and low levels of IL-10 were released by M1 macrophages[63-64]. However, on the other hand, M2 macrophages produced more IL-10 but less IL-12 and IL-23[65-66]. Th1 cytokines, such as IL-12 and IFN-γ, inhibited pathological angiogenesis in cornea, retina and choroid[23,67-69]. IFN-γ probably is a mediator of the inhibitory effects of IL-12 in Th1 response, and the downstream chemokines CXCL9 and CXCL10 may play some roles in the pathogenesis[67]. IL-18 negatively regulates pathological RNV by regressing the blood vessels in the OIR mouse model[70]. However, the role played by IL-18 in laser-induced CNV remains controversial[71-73]. It has been reported that a typical Th2 cytokine IL-10 promoted pathological neovascularization in both CNV and OIR models[35,63], while pretreatment of low-dose LPS suppressed CNV which possibly is regulated by the induction of IL-10[74]. Besides, Yang et al[75] reported that IL-10 suppressed experimental subretinal fibrosis formation, a following complication of CNV. All these studies provided controversial ideas of IL-10 in intraocular neovascularization. In contrast, another Th2 cytokine IL-4 attenuated laser-induced CNV, and this may resulted by different polarization and variable effects of subtypes in M2 macrophages (such as M2a, M2b and M2c)[76]. It is interesting that IL-23, as well as IL-17a neutralization inhibited ocular neovascularization[77-78]. The reason might be that IL-23 and IL-17 are involved in the Th17 pathway, which shows totally different effects in angiogenesis from Th1 pathway. IL-27 is involved in both induction of Th1 differentiation and inhibition of Th17 differentiation[79]. Hasegawa et al[80] demonstrated that IL-27 suppressed CNV formation via inhibition of VEGF. The immunological system of cytokines is very complicated, thus further studies are necessary to show the role played by Th17-related cytokines in macrophage polarization as well as intraocular neovascularization. Takeuchi et al[81] reported that Th2 and Th17-related immune responses could be involved in the pathological progress of PDR. Another study by Suzuki et al[82] demonstrated that intravitreal injection of bevacizumab affects the expressions of both pro-and anti-inflammatory cytokines, which indicated that anti-VEGF treatment might also modulate immune response through the networks of such cytokines. Thus, macrophages might include more phenotypes and/or subgroups that are related to different types of cytokines, which might also be involved in the intraocular neovascularization. CONCLUSION Increasing evidences proved that macrophages, as well as its polarization, should play an important role in developing and/ or inhibiting RNV and CNV. Recent studies demonstrated that M2 polarization of macrophages is thought to be more essential in promoting intraocular neovascularization. Moreover, a group of growth factors and cytokines are considered to participate in the pathogenesis caused by macrophages in the intraocular neovascular diseases. Therefore, specific molecular target associate with macrophages could be considered as a potential therapeutic treatment for the future clinical applications. ACKNOWLEDGEMENTS Foundations: Supported by National Natural Science Foundation of China (No.81371036; No.81700837); Department of Science and Technology, Hunan (No.2015TP2007); Japan Society for the Promotion of Science KAKENHI Grants (No.26293374; No.16K15734). Conflicts of Interest: Zhou YD, None; Yoshida S, None; Peng YQ, None; Kobayashi Y, None; Zhang LS, None; Tang LS, None. REFERENCES 1 Yoshida A, Yoshida S, Ishibashi T, Inomata H. Intraocular neovascularization. Histol Histopathol 1999;14(4):1287-1294. 2 Campochiaro PA. Ocular neovascularization. J Mol Med (Berl) 2013;91(3):311-321. 3 Gariano RF, Gardner TW. Retinal angiogenesis in development and disease. Nature 2005;438(7070):960-966. 4 Hiscott P, Wong D, Grierson I. Challenges in ophthalmic pathology: the vitreoretinal membrane biopsy. Eye (Lond) 2000;14(Pt 4):549-559. 5 Telander DG. Inflammation and age-related macular degeneration (AMD). Semin Ophthalmol 2011;26(3):192-197. 6 Ishikawa K, Kannan R, Hinton DR. Molecular mechanisms of subretinal fibrosis in age-related macular degeneration. Exp Eye Res 2016;142:19-25. 7 Osaadon P, Fagan XJ, Lifshitz T, Levy J. A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye (Lond) 2014;28(5):510-520. 8 Rizzo S, Genovesi-Ebert F, Di Bartolo E, Vento A, Miniaci S, Williams G. Injection of intravitreal bevacizumab (Avastin) as a preoperative adjunct before vitrectomy surgery in the treatment of severe proliferative diabetic retinopathy (PDR). Graefes Arch Clin Exp Ophthalmol 2008; 246(6):837-842. 9 Mintz-Hittner HA, Kuffel RR. Intravitreal injection of bevacizumab (Avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina 2008;28(6):831-838.
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© 2017, International Journal of Ophthalmology (c/o Editorial Office). All rights reserved.
PY - 2017/12/18
Y1 - 2017/12/18
N2 - ● Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intraocular neovascularization, and the polarization of M1 and M2 phenotypes plays extremely essential roles in the diverse functions of macrophages. Moreover, a large number of cytokines released by macrophages not only participate in macrophage polarization, but also associate with retinal and choroidal neovascular diseases. Therefore, macrophage might be considered as a novel therapeutic target to the treatment of pathological neovascularization in the eye. This review mainly summarizes diverse roles of macrophages and discusses the possible mechanisms in retinal and choroidal neovascularization.
AB - ● Macrophages are involved in angiogenesis, and might also contribute to the pathogenesis of intraocular neovascular diseases. Recent studies indicated that macrophages exert different functions in the process of intraocular neovascularization, and the polarization of M1 and M2 phenotypes plays extremely essential roles in the diverse functions of macrophages. Moreover, a large number of cytokines released by macrophages not only participate in macrophage polarization, but also associate with retinal and choroidal neovascular diseases. Therefore, macrophage might be considered as a novel therapeutic target to the treatment of pathological neovascularization in the eye. This review mainly summarizes diverse roles of macrophages and discusses the possible mechanisms in retinal and choroidal neovascularization.
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U2 - 10.18240/ijo.2017.12.18
DO - 10.18240/ijo.2017.12.18
M3 - Review article
AN - SCOPUS:85037587987
SN - 2222-3959
VL - 10
SP - 1902
EP - 1908
JO - International Journal of Ophthalmology
JF - International Journal of Ophthalmology
IS - 12
ER -