Long-term vision rescue by human neural progenitors in a rat model of photoreceptor degeneration.

Long-term vision rescue by human neural progenitors in a rat model of photoreceptor degeneration.
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DOI:
10.1167/iovs.08-1831
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发表时间:
2008-07
影响因子:
4.4
通讯作者:
Lund RD
Lund RD
中科院分区:
医学2区
文献类型:
--
作者:
Wang S;Girman S;Lu B;Bischoff N;Holmes T;Shearer R;Wright LS;Svendsen CN;Gamm DM;Lund RD

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作为先前研究的后续研究,表明人类皮质神经祖细胞(hNPCctx)在注射到皇家外科学院(RCS)大鼠的视网膜下腔后可以维持视力至少70天,作者研究了功能性拯救如何长时间保存以及这与视网膜完整性和供体细胞存活的关系。在出生后第21天(P),色素营养不良的RCS大鼠(n = 15)接受单侧视网膜下注射hNPCctx;对照大鼠(n = 10)仅接受培养基并且未处理。所有动物均维持口服环孢素A。通过在大约P90、P150和P280测量敏锐度(使用视动测试)和亮度阈值(从上级丘记录)连续监测功能。在功能测试后对眼睛进行组织学研究。在研究的所有时间点,hNPCctx处理的动物的敏锐度和亮度阈值均显著优于对照组(P < 0.001)。在P90、P150和P270时,敏锐度分别大于正常值的90%、82%和37%,而最佳抢救区域的亮度阈值在整个时间内保持相似。组织学研究显示大量的光感受器救援,甚至高达P280,尽管杆和锥形态进行性恶化。在P280时供体细胞仍然存在,并且没有观察到供体细胞过度生长的迹象。甚至在异种移植范例中,也观察到功能和相关形态学基质的长期拯救以及供体细胞存活。当进一步探索hNPCctx在治疗视网膜疾病中的应用潜力时,这是令人鼓舞的。(Invest Ophthalmol维斯科学。2008;49:3201-3206)
As a follow-up to previous studies showing that human cortical neural progenitor cells (hNPCctx) can sustain vision for at least 70 days after injection into the subretinal space of Royal College of Surgeons (RCS) rats, the authors examined how functional rescue is preserved over long periods and how this relates to retinal integrity and donor cell survival. Pigmented dystrophic RCS rats (n = 15) received unilateral subretinal injections of hNPCctx at postnatal day (P) 21; control rats (n = 10) received medium alone and were untreated. All animals were maintained on oral cyclosporine A. Function was monitored serially by measuring acuity (using an optomotor test) and luminance thresholds (recording from the superior colliculus) at approximately P90, P150, and P280. Eyes were processed for histologic study after functional tests. Acuity and luminance thresholds were significantly better in hNPCctx-treated animals than in controls (P < 0.001) at all time points studied. Acuity was greater than 90%, 82%, and 37% of normal at P90, P150, and P270, whereas luminance thresholds in the area of best rescue remained similar the whole time. Histologic studies revealed substantial photoreceptor rescue, even up to P280, despite progressive deterioration in rod and cone morphology. Donor cells were still present at P280, and no sign of donor cell overgrowth was seen. Long-term rescue of function and associated morphologic substrates was seen, together with donor cell survival even in the xenograft paradigm. This is encouraging when exploring further the potential for the application of hNPCctx in treating retinal disease. (Invest Ophthalmol Vis Sci. 2008;49: 3201–3206)
DOI: 10.1371/journal.pone.0000338
发表时间: 2007-03-28
期刊: PLOS ONE
影响因子: 3.7
作者:
Gamm, David M.;Wang, Shaomei;Lu, Bin;Girman, Sergei;Holmes, Toby;Bischoff, Nicholas;Shearer, Rebecca L.;Sauve, Yves;Capowski, Elizabeth;Svendsen, Clive N.;Lund, Raymond D.
通讯作者: Lund, Raymond D.
DOI: 10.1016/j.visres.2004.08.023
发表时间: 2005-02-01
期刊: VISION RESEARCH
影响因子: 1.8
作者:
Girman, S;Wang, S;Lund, RD
通讯作者: Lund, RD
DOI: 10.1016/s0042-6989(00)00081-x
发表时间: 2000-01-01
期刊: VISION RESEARCH
影响因子: 1.8
作者:
Prusky, GT;West, PWR;Douglas, RM
通讯作者: Douglas, RM
DOI: 10.1089/clo.2006.8.189
发表时间: 2006-09-01
期刊: CLONING AND STEM CELLS
影响因子: --
作者:
Lund, Raymond D.;Wang, Shaomei;Lanza, Robert
通讯作者: Lanza, Robert
DOI: 10.1038/81555
发表时间: 2000-11-01
期刊: NATURE GENETICS
影响因子: 30.8
作者:
Gal, A;Li, Y;Vollrath, D
通讯作者: Vollrath, D