연령관련황반변성 및 맥락막비후 신생혈관증 환자의 방수 사이토카인 농도와 맥락막두께의 상관분석
Aqueous Humor Cytokine Levels and Choroidal Thicknesses of Patients with Age‐related Macular Degeneration and Pachychoroid Neovasculopathy
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
목적: 삼출성 연령관련황반변성 및 맥락막비후 신생혈관증 환자에서 항혈관내피세포성장인자 주사 치료 전후 황반하 맥락막두께와방수 내 사이토카인 농도 변화의 상관성을 알아보고자 한다. 대상과 방법: 삼출성 연령관련황반변성 환자 11명 11안, 맥락막비후 신생혈관증 환자 9명 9안을 대상으로 항혈관내피세포성장인자 주사 시행 후 황반하 맥락막두께 변화를 분석하였다. 초기 및 4주째 방수를 채취하여 vascular endothelial growth factor (VEGF), soluble VEGF receptor‐2 (sVEGFR‐2), platelet‐derived growth factor (PDGF)‐AA, monocyte chemo‐attractant protein 1 (MCP‐1), interleukin (IL)‐6, IL‐8의 농도 변화를 살펴보고, 두 군 간에 방수 내 사이토카인 농도에 차이가 있는지 살펴보았다. 결과: 주사 치료 후 VEGF 및 PDGF‐AA의 농도는 유의하게 감소하였으며, sVEGFR‐2의 농도는 증가하였다. 주사 치료 전후 sVEGFR‐2 농도의 변화량은 맥락막두께 및 두께 변화량과 연관성을 보였는데, 맥락막이 상대적으로 얇고, 두께 변화가 작은 삼출성 연령관련황반변성 환자군에서 sVEGFR‐2 농도의 변화량이 컸다. 사이토카인 농도 간 상관관계 분석 결과 삼출성 연령관련황반변성 환자군에서는 MCP‐1, IL‐6 및 IL‐8 사이에 유의한 상관관계를 보였으나, 맥락막비후 신생혈관증 환자군에서는 sVEGFR‐2와 MCP‐1, MCP‐1과PDGF‐AA 간에 유의한 상관관계를 보였다. 결론: 맥락막이 상대적으로 얇은 삼출성 연령관련황반변성 환자군에서 주사 치료 후 sVEGFR‐2 농도의 상승폭이 컸으며, MCP‐1, IL‐6, IL‐8 등 염증성 사이토카인 수치 사이의 상관관계가 높게 나타났다. 이러한 결과는 두 질환군 간에 혈관신생인자나 염증성 사이토카인이 질병의 병태생리에 작용하는 방식에 차이가 있을 수 있음을 시사한다.
Abstract
Purpose: We sought correlations between the subfoveal choroidal thickness (SCT) and changes in the levels of aqueous humor cytokines before and after anti‐vascular endothelial growth factor (anti‐VEGF) treatment of patients with neovascular age‐related macular degeneration (nAMD) and pachychoroid neovasculopathy. Methods: We measured changes in the SCT and levels of aqueous humor cytokines (VEGF, soluble VEGF receptor‐2 [sVEGFR‐ 2], platelet‐derived growth factor [PDGF]‐AA, monocyte chemoattractant protein 1 [MCP‐1], interleukin [IL]‐6, and IL‐8) after anti‐ VEGF treatment of 11 eyes of 11 nAMD patients and nine eyes of nine pachychoroid neovasculopathy patients. The aqueous humor cytokine levels were compared between the two groups. Results: After anti‐VEGF treatment, the aqueous levels of VEGF and PDGF‐AA decreased significantly, whereas that of sVEGFR‐2 increased. The amount of change in sVEGFR‐2 concentration before and after anti‐VEGF treatment correlated with the SCT and its change after treatment. nAMD patients with relatively thin SCTs and smaller SCT changes after anti‐VEGF treatment showed greater increases in sVEGFR‐2 levels following treatment. We found significant correlations among the MCP‐1, IL‐6, and IL‐8 levels in the nAMD group, and between the sVEGFR‐2 and MCP‐1, and MCP‐1 and PDGF‐AA, levels in the pachychoroid neovasculopathy group. Conclusions: Patients with nAMD exhibited significant increases in aqueous sVEGFR‐2 levels following anti‐VEGF treatment and significant correlations among the levels of the inflammatory cytokines MCP‐1, IL‐6, and IL‐8, suggesting that angiogenic factors and inflammatory cytokines may affect the pathophysiologies of the two diseases differently.
참고문헌 (25)
- Lambert NG, "Risk factors and biomarkers of age-related macular degeneration", Prog Retin Eye Res, 54, pp.64~102 (2016)
- Rozing MP, "Age-related macular degeneration : a two-level model hypothesis", Prog Retin Eye Res, 76, pp.100825~ (2020)
- Margolis R, "A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes", Am J Ophthalmol, 147, pp.811~815 (2009)
- Ting DSW, "Choroidal remodeling in age-related macular degeneration and polypoidal choroidal vasculopathy : a 12-month prospective study", Sci Rep, 7, pp.7868~ (2017)
- Jonas JB, "Choroidal thickness in age-related macular degeneration", Retina, 34, pp.1149~1155 (2014)
- Lee JY, "Correlation between subfoveal choroidal thickness and the severity or progression of nonexudative age-related macular degeneration", Invest Ophthalmol Vis Sci, 54, pp.7812~7818 (2013)
- Pang CE, "Pachychoroid neovasculopathy", Retina, 35, pp.1~9 (2015)
- Miyake M, "Pachychoroid neovasculopathy and age-related macular degeneration", Sci Rep, 5, pp.16204~ (2015)
- Hata M, "Intraocular vascular endothelial growth factor levels in pachychoroid neovasculopathy and neovascular age-related macular degeneration", Invest Ophthalmol Vis Sci, 58, pp.292~298 (2017)
- Terao N, "Distinct aqueous humour cytokine profiles of patients with pachychoroid neovasculopathy and neovascular age-related macular degeneration", Sci Rep, 8, pp.10520~ (2018)
- Kato Y, "Complement activation products and cytokines in pachychoroid neovasculopathy and neovascular age-related macular degeneration", Invest Ophthalmol Vis Sci, 61, pp.39~ (2020)
- Tuncer I, "Choroidal thickness in relation to sex, age, refractive error, and axial length in healthy Turkish subjects", Int Ophthalmol, 35, pp.403~410 (2015)
- Read SA, "Longitudinal changes in choroidal thickness and eye growth in childhood", Invest Ophthalmol Vis Sci, 56, pp.3103~3112 (2015)
- Ng YS, "VEGF function in vascular pathogenesis", Exp Cell Res, 312, pp.527~537 (2006)
- Pradeep CR, "Expression of vascular endothelial growth factor(VEGF)and VEGF receptors in tumor angiogenesis and malignancies", Integr Cancer Ther, 4, pp.315~321 (2005)
- Masabumi Shibuya, "Differential Roles of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2 in Angiogenesis", BMB reports, 39(5), pp.469~478 (2006), 한국생화학분자생물학회
- Ebos JM, "Vascular endothelial growth factor-mediated decrease in plasma soluble vascular endothelial growth factor receptor-2 levels as a surrogate biomarker for tumor growth", Cancer Res, 68, pp.521~529 (2008)
- Szentirmai O, "Successful inhibition of intracranial human glioblastoma multiforme xenograft growth via systemic adenoviral delivery of soluble endostatin and soluble vascular endothelial growth factor receptor-2 : laboratory investigation", J Neurosurg, 108, pp.979~988 (2008)
- Agostini H, "A single local injection of recombinant VEGF receptor 2 but not of Tie2 inhibits retinal neovascularization in the mouse", Curr Eye Res, 30, pp.249~257 (2005)
- Albuquerque RJ, "Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth", Nat Med, 15, pp.1023~1030 (2009)
- Shibata MA, "The endogenous soluble VEGF receptor-2 isoform suppresses lymph node metastasis in a mouse immunocompetent mammary cancer model", BMC Med, 8, pp.69~ (2010)
- Jonas JB, "Monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in exudative age-related macular degeneration", Arch Ophthalmol, 128, pp.1281~1286 (2010)
- Droho S, "Macrophage-derived interleukin-6 is necessary and sufficient for choroidal angiogenesis", Sci Rep, 11, pp.18084~ (2021)
- Motohashi R, "Dynamics of soluble vascular endothelial growth factor receptors and their ligands in aqueous humour during ranibizumab for age-related macular degeneration", J Inflamm(Lond), 15, pp.26~ (2018)
- Tanaka A, "Dynamic change of aqueous concentrations of VEGF and its soluble receptors during the treatment of aflibercept in patients with age-related macular degeneration", Invest Ophthalmol Vis Sci, 55, pp.595~ (2014)