Knisely T L, Bleicher P A, Vibbard C A, Granstein R D
Massachusetts General Hospital, Boston.
Curr Eye Res. 1991 Aug;10(8):761-71. doi: 10.3109/02713689109013870.
Aqueous humor contains transforming growth factor-beta (TGF-beta) and other inhibitory factors for cellular proliferation. In the present study we investigated the possibility that these factors are produced locally by cells found within the iris and ciliary body. Iris and ciliary body (I/CB) cells or whole tissue explants from C57BL/6 mice produced soluble factors which inhibited both murine thymocyte and mink lung epithelial cell proliferation. Indomethacin partially blocked inhibition of thymocyte proliferation, but did not affect inhibition of Mv1 Lu proliferation. The inhibitory activity of culture supernatants was not blocked by neutralizing antibodies to TGF-beta 1 or TGF-beta 2. However, following acid activation of culture supernatants from both I/CB and corneal tissue, increased inhibitory activity consistent with activation of latent TGB-beta was detected. Antibody neutralization experiments demonstrated that this increase in activity was due primarily to TGF-beta 2 for I/CB tissue. Polymerase chain reaction (PCR) analysis of cDNA generated from I/CB tissue mRNA showed prominent fragments representing both TGF-beta 1 and TGF-beta 2 mRNA. Corneal tissue, however, showed a prominent fragment for TGF-beta 1 mRNA, but either no band or a barely detectable fragment for TGF-beta 2 mRNA. Therefore, it remains uncertain whether TGF-beta 2 mRNA is produced by the cornea in this strain. Overall, these results demonstrated that three distinct categories of substances inhibitory to proliferation may be locally produced by resident iris and ciliary body cells: 1) indomethacin sensitive products, 2) TGF-beta 2 in latent form, and 3) factors not blocked by indomethacin or anti-TGF-beta neutralizing antibodies. Products generated by these tissues may have important regulatory properties in the development of immune responses to antigens introduced into the anterior chamber.
房水中含有转化生长因子-β（TGF-β）和其他抑制细胞增殖的因子。在本研究中，我们调查了这些因子是否由虹膜和睫状体中的细胞局部产生。来自C57BL/6小鼠的虹膜和睫状体（I/CB）细胞或全组织外植体产生了可抑制小鼠胸腺细胞和水貂肺上皮细胞增殖的可溶性因子。吲哚美辛部分阻断了对胸腺细胞增殖的抑制作用，但不影响对Mv1 Lu增殖的抑制作用。培养上清液的抑制活性不受针对TGF-β 1或TGF-β 2的中和抗体的阻断。然而，在对I/CB和角膜组织的培养上清液进行酸激活后，检测到与潜伏TGB-β激活一致的抑制活性增加。抗体中和实验表明，这种活性增加主要归因于I/CB组织中的TGF-β 2。对从I/CB组织mRNA生成的cDNA进行聚合酶链反应（PCR）分析，显示出代表TGF-β 1和TGF-β 2 mRNA的显著片段。然而，角膜组织显示出TGF-β 1 mRNA的显著片段，但TGF-β 2 mRNA要么没有条带，要么是几乎检测不到的片段。因此，尚不确定该品系的角膜是否产生TGF-β 2 mRNA。总体而言，这些结果表明，驻留的虹膜和睫状体细胞可能在局部产生三类不同的抑制增殖的物质：1）吲哚美辛敏感产物，2）潜伏形式的TGF-β 2，以及3）不受吲哚美辛或抗TGF-β中和抗体阻断的因子。这些组织产生的产物可能在对引入前房的抗原的免疫反应发展中具有重要的调节特性。
