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New iPSC-model for Common Cause of Blindness Demonstrates Enormous Potential



Review of “An iPSC Patient Specific Model of CFH (Y402H) Polymorphism Displays Characteristic Features of AMD and Indicates a Beneficial Role for UV Light Exposure” from STEM CELLS by Stuart P. Atkinson

Age-related macular degeneration (AMD) represents an unfortunately common cause of blindness; a fact made worse by the lack of treatments to prevent progression of the “dry” form of the disease associated with the accumulation of cellular debris (or drüsen). In the hope of rectifying this situation, a team of researchers from the laboratory of Majlinda Lako (Newcastle University, UK) generated induced pluripotent stem cells (iPSCs) from patient-derived somatic cells carrying low- and high AMD-risk gene polymorphisms. Hallam et al. then redifferentiated these iPSCs into retinal pigment epithelial cells (iPSC-RPE) in the hope of developing a disease-specific model to better understand dry AMD progression and to test potential therapeutic agents [1].

The authors first reprogrammed patient dermal fibroblasts with non‐integrative Sendai viral vectors expressing Yamanaka reprogramming transgenes and then differentiated the resultant iPSCs into RPE via the application of a defined, serum- and feeder-free protocol. Low- and high-risk iPSC‐RPE cells displayed many similar features; however, high-risk iPSC‐RPE also specifically exhibited several characteristics associated with advanced AMD. This included increased expression of inflammatory markers, decreased expression of protective oxidative stress markers, elevated numbers of stress vacuoles, the accumulation of lipid droplets, and impaired autophagy. Importantly, high-risk iPSC-RPE also contained more substantial drüsen deposits, which altogether demonstrate their utility as a suitable model for AMD study.

Interestingly, the study also discovered that low-risk and high-risk iPSC-RPE reacted differently in response to stress stimuli - in this case, repeated doses of ultraviolet (UV) light. While UV light exposure led to an increase in inflammatory markers in the low-risk iPSC-RPE, UV light induced an elevated protective oxidative stress defense, reduced the number of vacuoles, and decreased the volume of drüsen deposits in high-risk iPSC-RPE. Therefore, this data proposes UV light and/or the induction of oxidative stress defense as potentially exciting new treatment options for patients with advanced dry AMD, in agreement with another related study [2].

Overall, the authors have displayed the enormous potential for their iPSC-based model system, which may represent an efficient means to understand disease pathology and the role of environmental, dietary, and lifestyle factors, and to test therapies for AMD before the initiation of lengthy and expensive trials [3-5].

To hear more on the application of this exciting new model for dry AMD, keep the Stem Cells Portal only a click away!


  1. Hallam D, Collin J, Bojic S, et al., An Induced Pluripotent Stem Cell Patient Specific Model of Complement Factor H (Y402H) Polymorphism Displays Characteristic Features of Age-Related Macular Degeneration and Indicates a Beneficial Role for UV Light Exposure. STEM CELLS 2017;35:2305-2320.
  2. Saini JS, Corneo B, Miller JD, et al., Nicotinamide Ameliorates Disease Phenotypes in a Human iPSC Model of Age-Related Macular Degeneration. Cell Stem Cell 2017;20:635-647 e7.
  3. Troutbeck R, Al-Qureshi S, and Guymer RH, Therapeutic targeting of the complement system in age-related macular degeneration: a review. Clin Exp Ophthalmol 2012;40:18-26.
  4. Schaal KB, Rosenfeld PJ, Gregori G, et al., Anatomic Clinical Trial Endpoints for Nonexudative Age-Related Macular Degeneration. Ophthalmology 2016;123:1060-79.
  5. Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, et al., Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study. Ophthalmology 2014;121:693-701.