营养因子 GDNF 和 BDNF 可改善视网膜片移植的功能。
Trophic factors GDNF and BDNF improve function of retinal sheet transplants.
机构信息
Anatomy and Neurobiology, Univ. of California, Irvine, CA, USA.
出版信息
Exp Eye Res. 2010 Nov;91(5):727-38. doi: 10.1016/j.exer.2010.08.022. Epub 2010 Sep 6.
The aim of this study was to compare glial-derived neurotrophic factor (GDNF) treatment with brain-derived neurotrophic factor (BDNF) treatment of retinal transplants on restoration of visual responses in the superior colliculus (SC) of the S334ter line 3 rat model of rapid retinal degeneration (RD). RD rats (age 4-6 weeks) received subretinal transplants of intact sheets of fetal retina expressing the marker human placental alkaline phosphatase (hPAP). Experimental groups included: (1) untreated retinal sheet transplants, (2) GDNF-treated transplants, (3) BDNF-treated transplants, (4) none surgical, age-matched RD rats, (5) sham surgery RD controls, (6) progenitor cortex transplant RD controls, and (7) normal pigmented rat controls. At 2-8 months after transplantation, multi-unit visual responses were recorded from the SC using a 40 ms full-field stimulus (-5.9 to +1 log cd/m(2)) after overnight dark-adaptation. Responses were analyzed for light thresholds, spike counts, response latencies, and location within the SC. Transplants were grouped into laminated or rosetted (more disorganized) transplants based on histological analysis. Visual stimulation of control RD rats evoked no responses. In RD rats with retinal transplants, a small area of the SC corresponding to the position of the transplant in the host retina, responded to light stimulation between -4.5 and -0.08 log cd/m(2), whereas the light threshold of normal rats was at or below -5 log cd/m(2) all over the SC. Overall, responses in the SC in rats with laminated transplants had lower response thresholds and were distributed over a wider area than rats with rosetted transplants. BDNF treatment improved responses (spike counts, light thresholds and responsive areas) of rats with laminated transplants whereas GDNF treatment improved responses from rats with both laminated and rosetted (more disorganized) transplants. In conclusion, treatment of retinal transplants with GDNF and BDNF improved the restoration of visual responses in RD rats; and GDNF appears to exert greater overall restoration than BDNF.
本研究旨在比较胶质细胞源性神经营养因子（GDNF）和脑源性神经营养因子（BDNF）治疗对 S334ter 线 3 型快速视网膜变性（RD）大鼠模型中视网膜移植物对视上丘（SC）视觉反应恢复的影响。RD 大鼠（4-6 周龄）接受表达人胎盘碱性磷酸酶（hPAP）标记物的完整胎儿视网膜片的视网膜下移植。实验组包括：（1）未治疗的视网膜片移植物，（2）GDNF 处理的移植物，（3）BDNF 处理的移植物，（4）无手术、年龄匹配的 RD 大鼠，（5）假手术 RD 对照，（6）祖皮质移植物 RD 对照，（7）正常色素大鼠对照。移植后 2-8 个月，在一夜暗适应后，使用 40ms 全视野刺激（-5.9 至+1log cd/m(2)）记录 SC 的多单位视觉反应。分析光阈值、尖峰计数、反应潜伏期和 SC 内的位置。根据组织学分析，将移植物分为层状或玫瑰花结状（更紊乱）移植物。对照 RD 大鼠的视觉刺激没有反应。在有视网膜移植物的 RD 大鼠中，SC 中与宿主视网膜中移植物位置相对应的一小部分区域对-4.5 至-0.08log cd/m(2)的光刺激有反应，而正常大鼠的光阈值在整个 SC 中都在-5log cd/m(2)或以下。总体而言，层状移植物大鼠的 SC 反应具有更低的反应阈值，并分布在比玫瑰花结状移植物大鼠更广泛的区域。BDNF 治疗改善了层状移植物大鼠的反应（尖峰计数、光阈值和反应区域），而 GDNF 治疗改善了层状和玫瑰花结状（更紊乱）移植物大鼠的反应。总之，用 GDNF 和 BDNF 治疗视网膜移植物可改善 RD 大鼠视觉反应的恢复；并且 GDNF 似乎比 BDNF 具有更大的整体恢复作用。
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