Cytokine Profiling in Patients with Polypoidal Choroidal Vasculopathy Before and After Intravitreal Injection of Ranibizumab

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2022 Nov 18

PMID 36398243

Authors

Tingting Sun

Jianhao Bai

Minli Wang

Le Liu

Qing Peng

Affiliations

Soon will be listed here.

Abstract

Objective: This study aims to investigate the cytokines profiling in the aqueous humor of patients with polypoidal choroidal vasculopathy (PCV) before and after intravitreal ranibizumab injection (IVR).

Methods: 14 patients clinically diagnosed with PCV and 15 cataract patients of similar age and gender (control group) were included. Throughout the cataract surgery and IVR, aqueous humor samples were collected from the PCV and control groups.

Results: The levels of macrophage inflammatory protein 1β (MIP-1β) and normal T cell expressed and secreted (RANTES) in PCV patients were significantly lower than control subjects (P=0.045 and P=0.004, respectively). The concentration of vascular endothelial growth factor-A (VEGF-A) was significantly higher than the control group (P=0.003). The level of MIP-1β was greatly increased in PCV patients compared to prior to IVR (P=0.001). After IVR, the level of VEGF-A in PCV patients were considerably lower compared to before IVR (P=0.001). There was no link between the expression of several cytokines (MCP-1, MIP-1, Eotaxin, G-CSF, IL-8, IL-6, IL-5, IP-10 and IFN-γ) in the aqueous humor of PCV patients before and after intravitreal ranibizumab injection (IVR). The association between IL-5 expression and central macular thickness (CMT) was discovered before IVR (P=0.02), however, the correlation between several cytokines (MCP-1, MIP-1, Eotaxin, G-CSF, IL-8, IL-6, IL-5, IP-10 and IFN-γ) was discovered in PCV patients after IVR.

Conclusion: Based on our findings, we discovered that the production of neovascularization in PCV patients is driven by both angiogenic and inflammatory factors, with a correlation seen between several cytokines.

References

Deshauer C, Morgan A, Ryan E, Handel T, Prestegard J, Wang X . Interactions of the Chemokine CCL5/RANTES with Medium-Sized Chondroitin Sulfate Ligands. Structure. 2015; 23(6):1066-77. PMC: 4456249. DOI: 10.1016/j.str.2015.03.024. View

Barcelos L, Coelho A, Russo R, Guabiraba R, Souza A, Bruno-Lima Jr G . Role of the chemokines CCL3/MIP-1 alpha and CCL5/RANTES in sponge-induced inflammatory angiogenesis in mice. Microvasc Res. 2009; 78(2):148-54. DOI: 10.1016/j.mvr.2009.04.009. View

Honczarenko M, Le Y, Glodek A, Majka M, Campbell J, Ratajczak M . CCR5-binding chemokines modulate CXCL12 (SDF-1)-induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the CXCR4 chemokine receptor. Blood. 2002; 100(7):2321-9. DOI: 10.1182/blood-2002-01-0248. View

Miyata M, Ooto S, Yamashiro K, Tamura H, Hata M, Ueda-Arakawa N . Five-year visual outcomes after anti-VEGF therapy with or without photodynamic therapy for polypoidal choroidal vasculopathy. Br J Ophthalmol. 2018; 103(5):617-622. DOI: 10.1136/bjophthalmol-2018-311963. View

Yannuzzi L, Sorenson J, Spaide R, Lipson B . Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina. 1990; 10(1):1-8. View

Sasaki S, Miyazaki D, Miyake K, Terasaka Y, Kaneda S, Ikeda Y . Associations of IL-23 with polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2012; 53(7):3424-30. DOI: 10.1167/iovs.11-7913. View

Lodi P, Garrett D, Kuszewski J, Tsang M, Weatherbee J, Leonard W . High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR. Science. 1994; 263(5154):1762-7. DOI: 10.1126/science.8134838. View

Yao L, Herlea-Pana O, Heuser-Baker J, Chen Y, Barlic-Dicen J . Roles of the chemokine system in development of obesity, insulin resistance, and cardiovascular disease. J Immunol Res. 2014; 2014:181450. PMC: 3987870. DOI: 10.1155/2014/181450. View

Balne P, Agrawal R, Au V, Lee B, Ghosh A, Sethu S . Dataset of plasma and aqueous humor cytokine profiles in patients with exudative age related macular degeneration and polypoidal choroidal vasculopathy. Data Brief. 2018; 19:1570-1573. PMC: 6141765. DOI: 10.1016/j.dib.2018.05.085. View

10.

Terasaki H, Miyake Y, Suzuki T, Nakamura M, Nagasaka T . Polypoidal choroidal vasculopathy treated with macular translocation: clinical pathological correlation. Br J Ophthalmol. 2002; 86(3):321-7. PMC: 1771039. DOI: 10.1136/bjo.86.3.321. View

11.

Wong C, Yanagi Y, Lee W, Ogura Y, Yeo I, Wong T . Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians. Prog Retin Eye Res. 2016; 53:107-139. DOI: 10.1016/j.preteyeres.2016.04.002. View

12.

Adams R, Alitalo K . Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol. 2007; 8(6):464-78. DOI: 10.1038/nrm2183. View

13.

Griffith J, Sokol C, Luster A . Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol. 2014; 32:659-702. DOI: 10.1146/annurev-immunol-032713-120145. View

14.

Matsuoka M, Ogata N, Otsuji T, Nishimura T, Takahashi K, Matsumura M . Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy. Br J Ophthalmol. 2004; 88(6):809-15. PMC: 1772169. DOI: 10.1136/bjo.2003.032466. View

15.

Anantharaman G, Sheth J, Bhende M, Narayanan R, Natarajan S, Rajendran A . Polypoidal choroidal vasculopathy: Pearls in diagnosis and management. Indian J Ophthalmol. 2018; 66(7):896-908. PMC: 6032720. DOI: 10.4103/ijo.IJO_1136_17. View

16.

Baltus T, von Hundelshausen P, Mause S, Buhre W, Rossaint R, Weber C . Differential and additive effects of platelet-derived chemokines on monocyte arrest on inflamed endothelium under flow conditions. J Leukoc Biol. 2005; 78(2):435-41. DOI: 10.1189/jlb.0305141. View

17.

Fan Q, Cheung C, Chen L, Yamashiro K, Ahn J, Laude A . Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians. J Hum Genet. 2017; 62(12):1049-1055. DOI: 10.1038/jhg.2017.83. View

18.

Keophiphath M, Rouault C, Divoux A, Clement K, Lacasa D . CCL5 promotes macrophage recruitment and survival in human adipose tissue. Arterioscler Thromb Vasc Biol. 2009; 30(1):39-45. DOI: 10.1161/ATVBAHA.109.197442. View

19.

Chen T, Chien S, Kuo H, Huang W, Sheen J, Lin T . High glucose-treated macrophages augment E-selectin expression in endothelial cells. J Biol Chem. 2011; 286(29):25564-73. PMC: 3138282. DOI: 10.1074/jbc.M111.230540. View

20.

Maruko I, Iida T, Saito M, Nagayama D, Saito K . Clinical characteristics of exudative age-related macular degeneration in Japanese patients. Am J Ophthalmol. 2007; 144(1):15-22. DOI: 10.1016/j.ajo.2007.03.047. View