ABSTRACT
Age-related macular degeneration (AMD) is characterized by visual impairment observed in elderly population. Two forms of the disease are generally described, the atrophic (AMDa) and exudative forms (AMDe). Up until now, no curative treatment is available for this disease. The retinal pigment epithelium (RPE) plays a central role in the pathogenesis of age-related macular degeneration. Here, involvement of RPE dysfunction in AMD onset and progression was analyzed by a comparison of transcriptome profiles of hiPSC-RPE derived from healthy individuals or individuals affected by AMDa or AMDe. The analysis highlighted almost 1000 genes differentially expressed between the three comparison groups. Among these genes, 33 genes were already known to be involved in AMD pathogenesis. To establish an AMD genetic signature, we focused on genes differentially expressed in both AMDa/e cell lines compared to control cells and focused on the three genes (ABCA1, RPN2, RB1CC1) that were related to lipidic homeostasis. Differences in level expression of these three genes are found not only in control and AMDa/e cell lines, but also between AMDa and AMDe populations.
Subject(s)
Homeostasis , Induced Pluripotent Stem Cells , Lipid Metabolism , Macular Degeneration , Retinal Pigment Epithelium , Cell Line , Homeostasis/genetics , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Lipid Metabolism/genetics , Macular Degeneration/genetics , Macular Degeneration/metabolism , Macular Degeneration/pathology , Retinal Pigment Epithelium/cytology , Retinal Pigment Epithelium/metabolism , RNA-Seq , Humans , Middle Aged , Aged , Aged, 80 and overABSTRACT
Alteration of the outer retina leads to various diseases such as age-related macular degeneration or retinitis pigmentosa characterized by decreased visual acuity and ultimately blindness. Despite intensive research in the field of retinal disorders, there is currently no curative treatment. Several therapeutic approaches such as cell-based replacement and gene therapies are currently in development. In the context of cell-based therapies, different cell sources such as embryonic stem cells, induced pluripotent stem cells, or multipotent stem cells can be used for transplantation. In the vast majority of human clinical trials, retinal pigment epithelial cells and photoreceptors are the cell types considered for replacement cell therapies. In this review, we summarize the progress made in stem cell therapies ranging from the pre-clinical studies to clinical trials for retinal disease.