Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chong Qing, China.
Curr Eye Res. 2012 Aug;37(8):749-58. doi: 10.3109/02713683.2012.697972. Epub 2012 Jun 12.
Retinitis pigmentosa (RP) is a group of genetic disorders and a slow loss of vision that is caused by a cascade of retinal degenerative events. We examined whether these retinal degenerative events were reduced after cultured mixtures of adult olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts (ONFs) were transplanted into the subretinal space of 1-month-old RCS rat, a classic model of RP.
The changes in retinal photoreceptors and Müller cells of RCS rats after cell transplantation were observed by the expression of recoverin and glial fibrillary acidic protein (GFAP), counting peanut agglutinin (PNA)-positive cone outer segments and calculating the relative apoptotic area. The retinal function was also evaluated by Flash electroretinography (ERG). To further investigate the mechanisms, by which OECs/ONFs play important roles in the transplanted retinas, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF) secretion of the cultured cells were analyzed by ELISA. The ability of OECs/ONFs to ingest porcine retinal outer segments and the amount of phagocytosis were compared with retinal pigment epithelium (RPE) cells.
Our research showed that the transplantation of OECs/ONFs mixtures restored recoverin expression, protected retinal outer segments, increased PNA-positive cone outer segments, reduced caspase-positive apoptotic figures, downregulated GFAP, and maintained the b-wave of the ERG. Cultured OECs/ONFs expressed and secreted NGF, BDNF, and bFGF which made contributions to assist survival of the photoreceptors. An in vitro phagocytosis assay showed that OECs, but not ONFs, phagocytosed porcine retinal outer segments, and the phagocytic ability of OECs was even superior to that of RPE cells.
These findings demonstrate that transplantation of OECs/ONFs cleaned up the accumulated debris in subretinal space, and provided an intrinsic continuous supply of neurotrophic factors. It suggested that transplantation of OECs/ONFs might be a possible future route for protection of the retina and reducing retinal degeneration in RP.
色素性视网膜炎（RP）是一组遗传疾病，也是一种由视网膜退行性事件级联导致的视力缓慢丧失。我们研究了成年嗅鞘细胞（OEC）和嗅神经成纤维细胞（ONF）培养混合物移植到 1 月龄 RCS 大鼠（RP 的经典模型）的视网膜下腔后，这些视网膜退行性事件是否减少。
通过回收蛋白和胶质纤维酸性蛋白（GFAP）的表达，观察细胞移植后 RCS 大鼠视网膜光感受器和 Muller 细胞的变化，计数花生凝集素（PNA）阳性的圆锥外节，并计算相对凋亡面积。视网膜功能也通过闪光视网膜电图（ERG）进行评估。为了进一步研究 OEC/ONF 在移植视网膜中发挥重要作用的机制，通过 ELISA 分析培养细胞分泌的神经生长因子（NGF）、脑源性神经营养因子（BDNF）和碱性成纤维细胞生长因子（bFGF）。比较 OEC/ONF 摄取猪视网膜外节的能力和吞噬量与视网膜色素上皮（RPE）细胞的差异。
我们的研究表明，OEC/ONF 混合物移植恢复了回收蛋白的表达，保护了视网膜外节，增加了 PNA 阳性的圆锥外节，减少了 caspase 阳性的凋亡细胞，下调了 GFAP，并维持了 ERG 的 b 波。培养的 OEC/ONF 表达并分泌 NGF、BDNF 和 bFGF，有助于辅助光感受器的存活。体外吞噬试验表明，OEC 而非 ONF 吞噬猪视网膜外节，且 OEC 的吞噬能力甚至优于 RPE 细胞。
这些发现表明，OEC/ONF 移植清除了视网膜下腔中积累的碎片，并提供了内在的持续神经营养因子供应。这表明 OEC/ONF 移植可能是保护视网膜和减少 RP 中视网膜变性的一种潜在未来途径。
