CONTROL OF CELL DIVISION IN THE OCULAR LENS

了解与年龄相关的晶状体上皮细胞的变化很重要。 由于美国十分之一的新失明病例是由 老年性白内障。这项工作的长期目标是确定 白内障前、后上皮细胞的功能变化 形成和老化。这一信息应进一步澄清 维持晶状体上皮细胞的透明性。 长期目标是确定：1)调节有丝分裂的因素 在体内和体外的晶状体上皮细胞中，2)晶状体 细胞对过氧化氢的解毒，以及3)如果对生长因子的反应和能力 对过氧化氢的解毒作用随着年龄的增长而变化。 具体目的是确定脑下垂体切除术的影响， 甲状腺切除和营养不良对晶状体有丝分裂的影响。 将分析上皮的整体数量和有丝分裂的数量 图像和DNA合成细胞的数量。IGF、T3和T4水平 将通过放射免疫分析和血清的有丝分裂原性来测量 经处理的动物将在培养的晶状体细胞上确定。 兔和人晶状体细胞长期生长的要求 将对无血清培养液进行研究。晶状体细胞对 多肽生长因子和增强细胞有丝分裂原的因子 这些多肽将被确定。结合位点数和 碘化胰岛素在青年和成人细胞上的表观解离常数 年长的兔子将被量化。免疫学技术与分子 将使用探头来证明晶状体特定功能的保留 在培养的细胞中。 幼年和老年兔晶状体上皮细胞解毒机制的研究 将测定H_2O_2。重点将放在GSH的作用上 氧化还原循环和酶，如GSH还原酶、GSH过氧化物酶和 超氧化物歧化酶，可能会随着年龄的增长而受损。线条将是 从编程为患白内障的小鼠和年龄匹配的小鼠建立的 努力确定非白内障对照的变化 上皮细胞可能是白内障前期和白内障的典型情况。这个 6月龄和1岁小鼠晶状体细胞过氧化氢解毒能力的研究 将会被确定。将使用TEM技术来定位过氧化氢酶和 正常和过氧化氢处理的晶状体上皮细胞中的过氧化物酶。

An understanding of age-related changes in the lens epithelium is important since one in ten new cases of blindness in the United States is caused by senile cataract. The long-term objective of this work is to identify functional changes in the epithelia which precede and accompany cataract formation and aging. This information should further clarify the role of epithelial cells in the maintenance of lens transparency. The long-term goals are to determine: 1) the factors that regulate mitosis in lens epithelia in vivo and in vitro, 2) the mechanism by which lens cells detoxify H2O2, and 3) if the response to growth factors and ability to detoxify H2O2 changes with age. Specific aims are to determine the influence of hypophysectomy, thyroidectomy and under-nutrition on mitosis in the ocular lens. Whole-mounts of the epithelium will be analyzed and the number of mitotic figures and DNA synthesizing cells quantitated. Levels of IGF, T3, and T4 will be measured via radioimmunoassay and the mitogenicity of serum from treated animals will be determined on cultured lens cells. The requirements for long-term growth of rabbit and human lens cells in serum-free medium will be investigated. The response of lens cells to polypeptide growth factors and to factors that enhance the mitogenicity of these peptides will be determined. The number of binding sites and apparent dissociation constant of iodinated insulin on cells from young and old rabbits will be quantitated. Immunological techniques and molecular probes will be used to demonstrate the retention of lens-specific function in cultured cells. The mechanism by which lens epithelia from young and old rabbits detoxifies H2O2 will be determined. Emphasis will be placed on the role of the GSH redox cycle and on enzymes, e.g. GSH reductase, GSH peroxidase, and superoxide dismutase, that may be impaired with age. Lines will be established from mice programmed to develop cataracts and from age-matched non-cataractous controls in an effort to determine changes in the epithelium that may typify precataractous and cataractous conditions. The H2O2 detoxifying ability of lens cells from 6-month and 1-year-old mice will be determined. TEM techniques will be used to localize catalase and peroxidase in normal and H2O2-treated lens epithelia.