Välimäki Juha, Uusitalo Hannu
Department of Ophthalmology, Päijät-Häme Central Hospital, Lahti, Finland.
Department of Ophthalmology, SILK, School of Medicine, University of Tampere, Tampere, Finland.
Acta Ophthalmol. 2015 Aug;93(5):450-456. doi: 10.1111/aos.12654. Epub 2015 Jan 14.
To investigate and compare functioning versus non-functioning glaucoma drainage implant (GDI) capsules for selective markers of extracellular matrix degradation and vascularity.
In three samples of both functioning and non-functioning blebs, immunohistochemistry was used to determine the expression of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, TIMP-3 and CD31. A non-functioning bleb was defined as IOP >21 mmHg or <20% reduction in IOP from baseline with maximal tolerated medication. The samples were classified into five grades based on immunostaining: no staining, no significant staining, mild, moderate or marked staining.
Expression of MMP-1, MMP-2 and MMP-3 was mostly low in both functioning and non-functioning blebs. However, immunostaining of MMP-9 was marked in samples taken from functioning GDIs and correlated with the presence of vascular profiles in the luminal bleb. CD31 immunoreactivity was more intense in the outer layers of the bleb than in the inner layers. In non-functioning blebs, immunoreactivity for TIMP-3 was significant through the whole bleb wall, but only mild in the inner zone of functioning blebs. TIMP-1 and TIMP-2 were barely detectable.
Staining of TIMP-3 was seen to be lower in the vicinity of the small blood vessels. In avascular bleb wall, increased expression of TIMP-3 suggests its potential role in the inhibition of angiogenesis as reported previously in vivo. The abundance of MMP-9 in bleb capsule wall of relatively old patients might lead to weakened bleb capsule wall architecture and increasing filtration of aqueous humour through the capsule, which are reflected in a lower IOP.
研究并比较功能性与非功能性青光眼引流植入物(GDI)囊泡中细胞外基质降解和血管生成的选择性标志物。
在功能性和非功能性滤泡的三个样本中,采用免疫组织化学法测定基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制因子-1(TIMP-1)、金属蛋白酶组织抑制因子-2(TIMP-2)、金属蛋白酶组织抑制因子-3(TIMP-3)和CD31的表达。非功能性滤泡定义为眼压>21 mmHg或在最大耐受药物治疗下眼压较基线降低<20%。根据免疫染色将样本分为五个等级:无染色、无明显染色、轻度、中度或重度染色。
功能性和非功能性滤泡中MMP-1、MMP-2和MMP-3的表达大多较低。然而,从功能性GDI获取的样本中MMP-9免疫染色明显,且与滤泡腔内血管轮廓的存在相关。CD31免疫反应性在滤泡外层比内层更强。在非功能性滤泡中,TIMP-3在整个滤泡壁的免疫反应性显著,但在功能性滤泡的内部区域仅为轻度。TIMP-1和TIMP-2几乎检测不到。
在小血管附近观察到TIMP-3染色较低。在无血管的滤泡壁中,TIMP-3表达增加表明其在抑制血管生成中可能发挥的作用,如先前体内研究报道。相对老年患者滤泡囊壁中MMP-9含量丰富可能导致滤泡囊壁结构减弱,房水通过囊泡的滤过增加,这反映在较低的眼压上。