Ji Yerina, Yu Wan-Qing, Eom Yun Sung, Bruce Farouk, Craft Cheryl Mae, Grzywacz Norberto M, Lee Eun-Jin
Neuroscience Graduate Program, University of Southern California, Los Angeles, California, United States Center for Vision Science and Technology, University of Southern California, Los Angeles, California, United States.
Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States.
Invest Ophthalmol Vis Sci. 2014 Dec 16;56(1):352-64. doi: 10.1167/iovs.14-15398.
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.
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.
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.
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.
正常视网膜中的光感受器阵列对视觉空间进行均匀且规则的采样。相比之下，视网膜色素变性（RP）的S334ter-3系大鼠模型视网膜中的视锥细胞会迁移形成环状镶嵌，留下大片几乎没有光感受器的空洞。类似的镶嵌现象也出现在患有其他形式视网膜营养不良的人类患者中。在本研究中，我们旨在研究金属蛋白酶组织抑制剂-1（TIMP-1）对S334ter-3系大鼠视网膜视锥细胞镶嵌的影响。我们关注TIMP-1是因为它是对细胞迁移很重要的细胞外基质调节因子之一。
进行免疫组织化学以显示M-视蛋白视锥细胞（M-视锥），并对结果进行量化，以统计学方式测试TIMP-1是否能将镶嵌恢复正常。特别是，测试集中在Voronoi和最近邻距离分析上。
我们的测试表明，TIMP-1导致S334ter-3系大鼠视网膜中M-视蛋白视锥环显著破坏，并导致几乎完全均匀的镶嵌。此外，TIMP-1使S334ter-3系大鼠视网膜中M-视锥的空间分布变得更接近随机，规律性降低。
这些发现证实，TIMP-1诱导S334ter-3系大鼠中的M-视锥镶嵌获得均匀性，但未达到正常视网膜镶嵌所见的规则程度。即使TIMP-1未能促进规则性，该药物对均匀性的影响似乎也非常显著，以至于TIMP-1可能是一种潜在的治疗药物。TIMP-1仅通过产生均匀性就改善了视野采样。
