Effects of human recombinant PEDF protein and PEDF-derived peptide 34-mer on choroidal neovascularization.
Effects of human recombinant PEDF protein and PEDF-derived peptide 34-mer on choroidal neovascularization.
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DOI：
10.1167/iovs.09-4455
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发表时间：
2010-03
影响因子：
4.4
通讯作者：
Becerra SP
中科院分区：
文献类型：
--
作者：
Amaral J;Becerra SP
色素上皮衍生因子（PEDF）是一种具有抗血管生成特性的丝氨酸蛋白酶抑制剂。以前，我们表明，PEDF注射在结膜下到达脉络膜。在这里，我们研究了PEDF多肽片段对血管发芽和结膜下给药后脉络膜新生血管（CNV）的影响。重组人PEDF（rhuPEDF）在其丝氨酸蛋白酶抑制剂暴露的环被有限的糜蛋白酶蛋白水解切割。使用合成的PEDF肽34聚体（Asp-Asn 77）和44聚体（Val 78-Thr 121）。进行离体鸡主动脉血管发芽测定。激光损伤Bruch膜诱导大鼠CNV。从损伤当天或损伤后第7天开始，每天进行结膜下注射（0.01-10皮摩尔蛋白质/天），持续5天。使用用Isolectin-Ib 4标记的脉络膜/RPE平板的光学切片定量新血管体积。通过脉络膜/RPE/视网膜横截面的免疫荧光评价PEDF分布。全长rhuPEDF，裂解rhuPEDF或肽34聚体表现出体外抗血管生成活性，而肽44聚体是无效的。激光损伤后，CNV病变周围的PEDF免疫染色减弱。结膜下给予rhuPEDF或34-mer（0.1皮摩尔/天）分别使CNV病变体积减少52%和47%，而44-mer的效果与溶媒注射相似。相对于溶媒注射，0.1和1皮摩尔rhuPEDF/天剂量分别使完全形成的CNV复合体体积减少45%和50%。用于抑制血管发芽和CNV的功能区域位于PEDF的34-mer区域内。此外，结膜下施用最佳范围剂量的rhuPEDF或34-mer可以抑制和消退大鼠CNV病变，表明这些药剂作为功能活性分子到达脉络膜/RPE复合物。
Pigment epithelium-derived factor (PEDF) is a serpin with antiangiogenic properties. Previously, we showed that PEDF injected in the subconjunctiva reaches the choroid. Here, we examine the effects of PEDF polypeptide fragments on vessel sprouting and on choroidal neovascularization (CNV) following subconjunctival administration. Recombinant human PEDF (rhuPEDF) was cleaved at its serpin-exposed loop by limited chymotrypsin proteolysis. Synthetic PEDF peptides 34-mer (Asp–Asn77) and 44-mer (Val78–Thr121) were used. Ex-vivo chick aortic vessel sprouting assays were performed. CNV was induced in rats by laser injury of Bruch’s membrane. Daily subconjunctival injections (0.01–10 picomoles protein/day) were performed for five days starting at day of injury or at the seventh day after injury. New vessel volumes were quantified using optical sections of choroid/RPE flat-mounts labeled with Isolectin-Ib4. PEDF distribution was evaluated by immunofluorescence of choroid/RPE/retina cross sections. Full-length rhuPEDF, cleaved rhuPEDF or peptide 34-mer exhibited ex-vivo antiangiogenic activity, while peptide 44-mer was inefficient. PEDF immunostaining around CNV lesions diminished after laser injury. Subconjunctival administration of rhuPEDF or 34-mer at 0.1 picomoles/day decreased CNV lesion volumes by 52% and 47%, respectively, while those of 44-mer were similar to vehicle injections. Doses of 0.1 and 1 picomole rhuPEDF/day decreased fully-developed CNV complex volumes by 45% and 50%, respectively, relative to vehicle injections. A functional region for inhibition of vessel sprouting and CNV resides within the 34-mer region of PEDF. Furthermore, subconjunctival administration of optimal range dosages of rhuPEDF or 34-mer can suppress and regress rat CNV lesions, demonstrating that these agents reach the choroid/RPE complex as functionally active molecules.
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影响因子：
3.4
作者：
Becerra, SP;Fariss, RN;Pfeffer, BA
通讯作者：
Pfeffer, BA
影响因子：
4.2
作者：
Campochiaro, PA;Nguyen, QD;Wei, LL
通讯作者：
Wei, LL
影响因子：
4.4
作者：
Apte, RS;Barreiro, RA;Ferguson, TA
通讯作者：
Ferguson, TA
DOI：
10.1093/jnci/91.19.1635
发表时间：
1999-10-06
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Fortier, AH;Nelson, BJ;Holaday, JW
通讯作者：
Holaday, JW
影响因子：
4.8
作者：
Bernard, Adrien;Gao-Li, Jacqueline;Li, Zhenlin
通讯作者：
Li, Zhenlin