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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

Inhibition of Experimental Age-Related Macular Degeneration by ZQMT in Mice

Author(s): Liu Yang*, Huan Meng*, Dan Luo, Tingting Deng, Li Miao, Bin Zou, Xiaofei Ge, Xiao Hu, Yu Liu, Xifang Li, Xiuli Deng, Shixin Guo, Juanran Liang, Tingting Chen, Xiaofeng Wen, Jing Jing Li, Lai Wei and Ming Jin

Volume 19, Issue 6, 2019

Page: [434 - 442] Pages: 9

DOI: 10.2174/1566524019666190425195706

Price: $65

Abstract

Background: Age-related macular degeneration (AMD) is a progressive and irreversible eye disease. The anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment of neovascular AMD. However, the expense for such treatment is quite high.

Methods: We used a traditional Chinese medicine ZQMT as an alternative therapeutic regimen for AMD. We employed two in vivo animal models mimicking dry and wet AMD respectively to assess the therapeutic efficacy of ZQMT on treating AMD-related retinopathy. AMD-related retinopathy in Crb1rd8 mice was evaluated from week 1 to 8 by fundus photography. Laser-induced choroidal neovascularization (CNV) was evaluated by fluorescein angiography and histopathology.

Results: ZQMT increased CX3CR1 expression in murine CD4+ T cells either cultured in vitro or directly isolated from animals treated with ZQMT. We also performed both in vitro and in vivo studies to confirm that ZQMT has no apparent toxic effects. ZQMT alleviated AMD-related retinopathy in both Crb1rd8 and CNV models. Depletion of CCL2 and CX3CR1 in Crb1rd8 mice abolished the efficacy of ZQMT, suggesting that CCL2 and/or CX3CR1 may underlie the mechanisms of ZQMT in treating AMD-related retinopathy in mice.

Conclusion: In summary, our study supports the protective roles of a traditional Chinese medicine ZQMT in AMD.

Keywords: Age-related macular degeneration, traditional Chinese medicine, CX3CR1, ZQMT, CCL2, VEGF.

« Previous Next »
[1]
Mitchell P, Liew G, Gopinath B, Wong TY. Age-related macular degeneration. Lancet 2018; 392(10153): 1147-59.
[2]
Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis. Lancet Glob Health 2014; 2(2): e106-16.
[3]
Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K. Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci 2016; 73(9): 1765-86.
[4]
Parmeggiani F, Sorrentino FS, Romano MR, et al. Mechanism of inflammation in age-related macular degeneration: an up-to-date on genetic landmarks. Mediators Inflamm 2013; 2013: 435607.
[5]
Raoul W, Auvynet C, Camelo S, et al. CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axes and their possible involvement in age-related macular degeneration. J Neuroinflammation 2010; 7: 87.
[6]
Falk MK, Singh A, Faber C, Nissen MH, Hviid T, Sorensen TL. CX3CL1/CX3CR1 and CCL2/CCR2 chemokine/ chemokine receptor complex in patients with AMD. PLoS One 2014; 9(12): e112473.
[7]
Combadiere C, Feumi C, Raoul W, et al. CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration. J Clin Invest 2007; 117(10): 2920-8.
[8]
Despriet DD, Bergen AA, Merriam JE, et al. Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related macular degeneration. Invest Ophthalmol Vis Sci 2008; 49(1): 364-71.
[9]
Mattapallil MJ, Wawrousek EF, Chan CC, et al. The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci 2012; 53(6): 2921-7.
[10]
Zhang J, Tuo J, Cao X, Shen D, Li W, Chan CC. Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient mice on Crb1(rd8) background. Synapse 2013; 67(8): 515-31.
[11]
Chen M, Hombrebueno JR, Luo C, et al. Age- and light-dependent development of localised retinal atrophy in CCL2(-/-)CX3CR1(GFP/GFP) mice. PLoS One 2013; 8(4): e61381.
[12]
Imai T, Hieshima K, Haskell C, et al. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 1997; 91(4): 521-30.
[13]
Ma W, Wong WT. Aging changes in retinal microglia and their relevance to age-related retinal disease. Adv Exp Med Biol 2016; 854: 73-8.
[14]
Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nat Rev Immunol 2013; 13(12): 875-87.
[15]
Tuo J, Bojanowski CM, Zhou M, et al. Murine ccl2/cx3cr1 deficiency results in retinal lesions mimicking human age-related macular degeneration. Invest Ophthalmol Vis Sci 2007; 48(8): 3827-36.
[16]
Song L. The observation of clinical therapeutic efficacy of ZQMT on non-ischemic retinal vein occlusion. Chin J Clin Rat Drug Use 2014; 7(36): 138-9.
[17]
Jin M, Zhang Y, Pan L, Dou R, Nussenblatt RB, Wei L. The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor. J Transl Med 2012; 10: 118.
[18]
Zhang W, Li Y, Lin J, et al. Comparison of hematoxylin-eosin staining and methyl violet staining for displaying ghost cells. Eye Sci 2013; 28(3): 140-3.
[19]
Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration. Neuron 2012; 75(1): 26-39.
[20]
Ding X, Patel M, Chan CC. Molecular pathology of age-related macular degeneration. Prog Retin Eye Res 2009; 28(1): 1-18.
[21]
Bowes Rickman C, Farsiu S, Toth CA, Klingeborn M. Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging. Invest Ophthalmol Vis Sci 2013; 54(14): ORSF68-80.
[22]
Prasad PS, Schwartz SD, Hubschman JP. Age-related macular degeneration: current and novel therapies. Maturitas 2010; 66(1): 46-50.
[23]
Leung E, Landa G. Update on current and future novel therapies for dry age-related macular degeneration. Expert Rev Clin Pharmacol 2013; 6(5): 565-79.
[24]
Pieramici DJ, Rabena MD. Anti-VEGF therapy: Comparison of current and future agents. Eye (Lond) 2008; 22(10): 1330-6.
[25]
Hussain RM, Hariprasad SM, Ciulla TA. Treatment burden in neovascular AMD: Visual acuity outcomes are associated with anti-VEGF injection frequency. Ophthalmic Surg Lasers Imaging Retina 2017; 48(10): 780-4.
[26]
Liu Y, Yin HJ, Shi DZ, Chen KJ. Chinese herb and formulas for promoting blood circulation and removing blood stasis and antiplatelet therapies. Evid Based Complement Alternat Med 2012; 2012: 184503.
[27]
Duan L, Xiong X, Hu J, Liu Y, Li J, Wang J. Panax notoginseng saponins for treating coronary artery disease: A functional and mechanistic overview. Front Pharmacol 2017; 8: 702.
[28]
Melo PA, do Nascimento MC, Mors WB, Suarez-Kurtz G. Inhibition of the myotoxic and hemorrhagic activities of crotalid venoms by Eclipta prostrata (Asteraceae) extracts and constituents. Toxicon 1994; 32(5): 595-603.
[29]
Wang S, Cunnusamy K. Pharmaceutical composition for treating macular degeneration (WO2012079419). Expert Opin Ther Pat 2013; 23(2): 269-72.
[30]
Jin M, Dai H, Zhang X, et al. A traditional chinese patent medicine ZQMT for neovascular age- related macular degeneration: A multicenter randomized clinical trial. Curr Mol Med 2018; 18(9): 622-9.
[31]
Luhmann UF, Lange CA, Robbie S, et al. Differential modulation of retinal degeneration by Ccl2 and Cx3cr1 chemokine signalling. PLoS One 2012; 7(4): e35551.
[32]
Ambati J, Anand A, Fernandez S, et al. An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat Med 2003; 9(11): 1390-7.

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