Semkova Irina, Kreppel Florian, Welsandt Gerhard, Luther Thomas, Kozlowski Jolanta, Janicki Hanna, Kochanek Stefan, Schraermeyer Ulrich
Center for Molecular Medicine Cologne (ZMMK), Center of Ophthalmology, Department of Retinal Surgery, Institute for Anatomy, University of Cologne, Kerpener Strasse 34, D-50931 Cologne, Germany.
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13090-5. doi: 10.1073/pnas.202486199. Epub 2002 Sep 18.
Age-related macular degeneration (ARMD) is the leading cause for visual impairment and blindness in the elder population. Laser photocoagulation, photodynamic therapy and excision of neovascular membranes have met with limited success. Submacular transplantation of autologous iris pigment epithelial (IPE) cells has been proposed to replace the damaged retinal pigment epithelium following surgical removal of the membranes. We tested our hypothesis that the subretinal transplantation of genetically modified autologous IPE cells expressing biological therapeutics might be a promising strategy for the treatment of ARMD and other retinal disorders. Pigment epithelium-derived factor (PEDF) has strong antiangiogenic and neuroprotective activities in the eye. Subretinal transplantation of PEDF expressing IPE cells inhibited pathological choroidal neovascularization in rat models of laser-induced rupture of Bruch's membrane and of oxygen induced ischemic retinopathy. PEDF expressing IPE transplants also increased the survival and preserved rhodopsin expression of photoreceptor cells in the RCS rat, a model of retinal degeneration. These findings suggest a promising concept for the treatment of ARMD and other retinal disorders.
年龄相关性黄斑变性（ARMD）是老年人群视力损害和失明的主要原因。激光光凝、光动力疗法和新生血管膜切除术取得的成功有限。有人提出进行自体虹膜色素上皮（IPE）细胞的黄斑下移植，以在手术切除膜后替代受损的视网膜色素上皮。我们检验了这样一个假设，即表达生物治疗剂的基因修饰自体IPE细胞的视网膜下移植可能是治疗ARMD和其他视网膜疾病的一种有前景的策略。色素上皮衍生因子（PEDF）在眼中具有强大的抗血管生成和神经保护活性。在激光诱导的 Bruch 膜破裂和氧诱导的缺血性视网膜病变大鼠模型中，视网膜下移植表达PEDF的IPE细胞可抑制病理性脉络膜新生血管形成。在视网膜变性模型RCS大鼠中，表达PEDF的IPE移植还提高了光感受器细胞的存活率并保留了视紫红质的表达。这些发现提示了一种治疗ARMD和其他视网膜疾病的有前景的理念。
