The effect of TIMP-1 on the cone mosaic in the retina of the rat model of retinitis pigmentosa.
The effect of TIMP-1 on the cone mosaic in the retina of the rat model of retinitis pigmentosa.
复制标题
TIMP-1对色素性视网膜炎大鼠模型视网膜锥体镶嵌的影响。
DOI：
10.1167/iovs.14-15398
复制
发表时间：
2014
影响因子：
4.4
通讯作者：
Lee,Eun-Jin
中科院分区：
文献类型：
--
作者：
Ji,Yerina;Yu,Wan-Qing;Eom,YunSung;Bruce,Farouk;Craft,CherylMae;Grzywacz,NorbertoM;Lee,Eun-Jin
目的：在正常视网膜中发现的光感受器阵列提供视觉空间的均匀和规则的采样。相比之下，RP的S334 ter-line-3大鼠模型的视网膜中的视锥细胞迁移以形成镶嵌环，留下具有很少或没有光感受器的大孔。类似的马赛克出现在患有其他形式视网膜营养不良的人类患者中。本研究旨在探讨基质金属蛋白酶组织抑制剂-1（TIMP-1）对S334 ter-line-3大鼠视网膜视锥细胞镶嵌的影响。我们关注TIMP-1，因为它是细胞迁移重要的细胞外基质的调节剂之一。进行免疫组织化学以显示M-视蛋白视锥细胞（M-cone），并对结果进行定量以统计学检验TIMP-1是否使镶嵌恢复正常。特别是，测试重点关注Voronoi和最近邻距离分析。结果：我们的测试表明，TIMP-1导致S334 ter-line-3大鼠视网膜中M-视蛋白视锥环的显著破坏，并导致几乎完全均匀的镶嵌。此外，TIMP-1诱导S334 ter-line-3大鼠视网膜中的M-视锥空间分布变得更接近随机，规律性降低。这些发现证实了TIMP-1诱导S334 ter-line-3中的M-视锥嵌合体获得均匀性，而没有达到正常视网膜嵌合体中所见的规则性程度。即使TIMP-1不能促进规律性，这种药物对均匀性的影响似乎是如此引人注目，TIMP-1可能是一种潜在的治疗剂。TIMP-1仅仅通过引起均匀性来改善视野的采样。
Purpose.: The array of photoreceptors found in normal retinas provides uniform and regular sampling of the visual space. In contrast, cones in retinas of the S334ter-line-3 rat model for RP migrate to form a mosaic of rings, leaving large holes with few or no photoreceptors. Similar mosaics appear in human patients with other forms of retinal dystrophy. In the current study, we aimed to investigate the effect of tissue inhibitor of metalloproteinase-1 (TIMP-1) on the mosaic of cones in S334ter-line-3 rat retinas. We focused on TIMP-1 because it is one of the regulators of the extracellular matrix important for cellular migration.Methods.: Immunohistochemistry was performed to reveal M-opsin cone cells (M-cone) and the results were quantified to test statistically whether or not TIMP-1 restores the mosaics to normal. In particular, the tests focused on the Voronoi and nearest-neighbor distance analyses.Results.: Our tests indicated that TIMP-1 led to significant disruption of the M-opsin cone rings in S334ter-line-3 rat retinas and resulted in almost complete homogeneous mosaics. In addition, TIMP-1 induced the M-cone spatial distribution to become closer to random with decreased regularity in S334ter-line-3 rat retinas.Conclusions.: These findings confirm that TIMP-1 induced M-cone mosaics in S334ter-line-3 to gain homogeneity without reaching the degree of regularity seen in normal retinal mosaics. Even if TIMP-1 fails to promote regularity, the effects of this drug on homogeneity appear to be so dramatic that TIMP-1 may be a potential therapeutic agent. TIMP-1 improves sampling of the visual field simply by causing homogeneity.