Personalized Drug Screening for Patients with Age-related Macular Degeneration using iPSC-RPE

Age-related macular degeneration (AMD) is a chronic disease that causes central vision loss and affects one's ability to read, drive, and recognize faces. There are currently no treatments for “dry” AMD, which includes ~80% of AMD patients in Minnesota. Dry AMD is associated with death of the retinal pigment epithelial (RPE) cells that is largely due to a loss in mitochondrial function.The overall goal of this research is to develop a therapy for patients with dry AMD by identifying drugs that will enhance mitochondrial function, thereby preserving the RPE.

Research Focus: age-related macular degeneration

Year 1 Progress Report:

Age Related Macular Degeneration (AMD) is a debilitating disease where individuals progressively lose their vision due to the death of retinal pigment epithelium (RPE) cells in the retina. There is a high prevalence of AMD among individuals with ancestry from Northern European countries, which includes a large portion of Minnesota’s population.  Currently there are no effective therapies to prevent or cure AMD. The work supported by this grant uses RPE generated from induced pluripotent stem cells (iPSCs) derived from individuals with AMD to test compounds that might be used in patients to prevent loss of RPE and preserve vision. In the first year of this grant, we have collected small biopsies of conjunctival cells from patients diagnosed with AMD and reprogrammed these cells into patient-specific iPSCs that can be differentiated into RPE cells for drug screening. We have also used iPSC-RPE cells to start testing a library of drugs to see if they are able to enhance or restore mitochondrial function. Mitochondria are the energy producing organelles in cells and loss of mitochondrial function in the RPE of individuals with AMD has been indicated as one of the potential causes of RPE death in this disease. Our preliminary results in the first year of the grant have highlighted that individual iPSC-RPE respond differently to the drugs, indicating the importance of using each patient’s iPSC-RPE to find their optimal treatment. Testing cells derived from every AMD patient will require increased scaling of our approach using automation. In the first year of this grant we have begun to utilize the robotic cell culture equipment available at the UMN Stem Cell Institute to automate our iPSC-RPE differentiation and drug screening workflow. Automation will allow us to increase scale to a level that will be necessary to apply this personalized medicine approach to treating AMD patients.

Final Progress Report:

In the first year of this grant, we collected small biopsies of conjunctival cells from patients diagnosed with AMD and reprogrammed these cells into patient-specific iPSCs that can be differentiated into RPE cells for drug screening. While the COVID 19 pandemic prevented additional participant recruitment for our studies during 2020 and so far in 2021, we have continued to reprogram the conjunctival cells previously collected from the living AMD donors into iPSC-RPE. These iPSC-RPE lines are being used to test a library of drugs to see if they are able to enhance or restore mitochondrial function. Mitochondria are the energy producing organelles in cells and loss of mitochondrial function in the RPE of individuals with AMD has been indicated as one of the potential causes of RPE death in this disease. Our results in the period of the grant have highlighted that iPSC-RPE from different individuals can respond differently to the drugs, indicating the importance of using each patient’s iPSC-RPE to find their optimal treatment. Testing cells derived from every AMD patient requires increased scaling of our approach using automation. As part of this grant, we have begun to utilize the robotic cell culture equipment available at the UMN Stem Cell Institute to automate our iPSC-RPE differentiation and drug screening workflow. Automation will allow us to increase scale to a level that will be necessary to apply this personalized medicine approach to treating AMD patients.