1] Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
Histopathology Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Lab Invest. 2014 Jun;94(6):674-82. doi: 10.1038/labinvest.2014.60. Epub 2014 Apr 7.
Platelet-derived growth factor (PDGF)-C is a member of the PDGF family and is critical for neuronal survival in the central nervous system. We studied the possible survival and antiapoptotic effects of PDGF-C on focal retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)] (DKO rd8) background mice, a model for progressive and focal retinal degeneration. We found no difference in transcript and protein expression of PDGF-C in the retina between DKO rd8 mice and wild type (WT, C57BL/6N). Recombinant PDGF-CC protein (500 ng/eye) was injected intravitreally into the right eye of DKO rd8 mice with phosphate-buffered saline as controls into the left eye. The retinal effects of PDGF-C were assessed by fundoscopy, ocular histopathology, A2E levels, apoptotic molecule analysis, and direct flat mount retinal vascular labeling. We found that the PDGF-CC-treated eyes showed slower progression or attenuation of the focal retinal lesions, lesser photoreceptor and retinal pigment epithelial degeneration resulting in better-preserved photoreceptor structure. Lower expression of apoptotic molecules was detected in the PDGF-CC-treated eyes than in controls. In addition, no retinal neovascularization was observed after PDGF-CC treatment. Our results demonstrate that PDGF-C potently ameliorates photoreceptor degeneration via the suppression of apoptotic pathways without inducing retinal angiogenesis. The protective effects of PDGF-C suggest a novel alternative approach for potential age-related retinal degeneration treatment.
血小板衍生生长因子 (PDGF)-C 是 PDGF 家族的成员，对中枢神经系统中的神经元存活至关重要。我们研究了 PDGF-C 对 Ccl2(-/-)/Cx3cr1(-/-)背景下 C57BL/6N [Crb1(rd8)] (DKO rd8) 小鼠局灶性视网膜病变的可能存活和抗凋亡作用，该模型用于进行性和局灶性视网膜变性。我们发现 DKO rd8 小鼠和野生型 (WT，C57BL/6N) 之间视网膜中 PDGF-C 的转录本和蛋白表达没有差异。将重组 PDGF-CC 蛋白 (500ng/眼) 玻璃体腔内注射到 DKO rd8 小鼠的右眼，左眼注射磷酸盐缓冲盐水作为对照。通过眼底镜检查、眼组织病理学、A2E 水平、凋亡分子分析和直接平展视网膜血管标记来评估 PDGF-C 的视网膜作用。我们发现，PDGF-CC 处理的眼睛显示出局灶性视网膜病变的进展或衰减更慢，光感受器和视网膜色素上皮变性更少，导致光感受器结构更好地保存。与对照组相比，PDGF-CC 处理的眼睛中凋亡分子的表达水平较低。此外，PDGF-CC 治疗后未观察到视网膜新生血管形成。我们的结果表明，PDGF-C 通过抑制凋亡途径有力地改善了光感受器变性，而没有诱导视网膜血管生成。PDGF-C 的保护作用表明了一种治疗与年龄相关的视网膜变性的新方法。
