Clinical Eye Research Division, Department of Ophthalmology, Zealand University Hospital, Roskilde, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Acta Ophthalmol. 2019 Feb;97(1):84-90. doi: 10.1111/aos.13894. Epub 2018 Oct 4.
Tissue inhibitor of metalloproteinase (TIMP) is known to play a role in age-related macular degeneration (AMD). We wished to investigate alterations in different late stages of AMD: neovascular AMD and geographic atrophy (GA).
This was a prospective case-control study. A total of 125 participants were included consecutively during a period of 18 months. We included 46 patients with neovascular AMD, 46 patients with GA without any sign of choroidal neovascularization in either eye, and 33 healthy aged controls. Patients with immune-affecting disorders were not included. Commercial immunoassay kits were used to quantify levels of TIMP-1, TIMP-3, MMP-2 and MMP-9 in blood plasma.
We found that patients with neovascular AMD had lower plasma concentration of TIMP-3 (p = 0.028) than healthy controls. Patients with GA had higher plasma levels of TIMP-1 (p < 0.001) and MMP-9 (p = 0.022) compared to healthy controls. Also, we found that TIMP-1 levels in patients with GA increased with age (Spearman's rho = 0.04, p = 0.006).
Matrix metalloproteinases (MMPs) and TIMPs, which are known to be involved in age-related changes in Bruch's membrane, are significantly altered systemically, suggesting the presence of an imbalance in the homeostasis of the extracellular matrix. These imbalances may explain differences in the clinical manifestation of late AMD.
金属蛋白酶组织抑制剂（TIMP）在年龄相关性黄斑变性（AMD）中起作用。我们希望研究 AMD 的不同晚期阶段（新生血管性 AMD 和地理萎缩（GA））的变化。
这是一项前瞻性病例对照研究。在 18 个月的时间内连续纳入了 125 名参与者。我们纳入了 46 名新生血管性 AMD 患者、46 名双眼均无脉络膜新生血管化的 GA 患者和 33 名健康老年对照者。未纳入患有免疫性疾病的患者。使用商业免疫测定试剂盒定量血浆中 TIMP-1、TIMP-3、MMP-2 和 MMP-9 的水平。
我们发现新生血管性 AMD 患者的 TIMP-3 血浆浓度较低（p=0.028）。GA 患者的 TIMP-1（p<0.001）和 MMP-9（p=0.022）血浆水平高于健康对照组。此外，我们发现 GA 患者的 TIMP-1 水平随年龄增加而增加（Spearman's rho=0.04，p=0.006）。
已知参与 Bruch 膜年龄相关性变化的基质金属蛋白酶（MMPs）和 TIMPs 在系统中发生了显著改变，这表明细胞外基质的动态平衡存在失衡。这些失衡可能解释了晚期 AMD 临床表现的差异。
