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 laserinduced 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.
In the western world in individuals over 60 years of age, age-related macular degeneration (ARMD) is the primary cause for visual impairment and blindness. Pathological changes in the retinal pigment epithelium (RPE) and in the choriocapillaris are associated with the progressive degeneration of macular photoreceptor cells. Vision loss in patients with the exudative form of ARMD (wet ARMD) is caused by the formation of subretinal fibrovascular membranes during a late stage of the disease. When this occurs it sometimes can be ablated by laser photocoagulation or photodynamic therapy, but neither treatment addresses underlying stimuli for blood vessel growth. Therefore, recurrent disease is a problem of significant clinical relevance. Surgical excision of submacular neovascular membranes leads to the additional damage of the RPE (1), a cell type that is known to play a central role in the homeostasis of the retina having phagocytic, metabolic, neurotrophic, antioxidative, and antiangiogenic functions. The most frequent form of ARMD (dry ARMD) is characterized by primary degeneration and atrophy of the RPE layer. Subretinal transplantation of autologous (from the same patient) iris pigment epithelial (IPE) cells has been a recent experimental treatment strategy to functionally replace the lost or damaged RPE in the macular area (2, 3). The IPE is anatomically continuous with the RPE and has the same embryonic origin. In vitro, IPE cells share functional properties with RPE cells such as phagocytosis (4, 5), degradation of rod outer segments (ROS) (6), and synthesis of trophic factors (7). However, autologous transplantation of IPE cells has not resulted in a prolonged improvement of the vision of ARMD patients, potentially because of the lack of expression of one or several (so far unknown) factors tha...