Age-related macular degeneration (AMD) is the leading cause of vision loss and legal blindness in higher-resource countries. The progressive and degenerative diseasewhich causes irreversible vision lossis caused by the dysfunction and death of the retinal pigment epithelium (RPE) and photoreceptors.
induced pluripotent stem cells from AMD patients and healthy individuals were transformed to RPE cells. These cells enabled transcriptomics and proteomics methods to identify molecular pathways that were significantly upregulated in one type of AMD geographic atrophy. The findings suggest that improved diagnosis and treatment of AMD may be possible.
Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration are published in Nature Communications.
Weve investigated the effect of genetic variations on the cells involved in age-related macular degeneration. At the smallest scale weve narrowed down specific kinds of cells to pinpoint the genetic markers of this disease, according to Joseph Powell, PhD, director of cellular science at the Garvan Institute of Medical Research. This is the basis of precision medicine, where we can then assess what therapies might be most beneficial for a persons genetic profile of disease.
[Grace Lidgerwood]Fresh fluorescent imaging of the retinal pigment epithelium The researchers incorporated transcriptional profiles of 127,659 RPE cells from 43 individuals with geographic atrophy (one of the two types of AMD) and 36 controls with genotype data.
RPE cells run along the retina's back, and are essential to the body's health and function. Their degeneration is associated with the death of photoreceptors, which are responsible for AMD's degeneration.
Analysis of 127,659 cells revealed molecular signatures associated with AMD. More specifically, they identified 445 expression quantitative trait loci in cis that are associated with disease status and specific to RPE subpopulations.
Five significant protein quantitative trait loci were identified, two of which have variants with cis-expression quantitative trait loci, including proteins involved in mitochondrial biology and neurodegeneration.
Further investigation of mitochondrial metabolism revealed mitochondrial dysfunction as a major constitutive difference between patients with geographic atrophy and patients with geographic atrophy.
The authors concluded that the molecular signatures might be used to screen for treatments using patient-specific cells in a dish. Ultimately, we are interested in matching the genetic profile of a patient to the best medicine for that patient. We must test how they function in cells relevant to the disease, said Alice Pebay, PhD, professor in the department of anatomy and physiology at the University of Melbourne.
According to Alex Hewitt, the Menzies Institute for Medical Research in Tasmania and the Centre for Eye Research Australia, we have been developing a program of research that included stem cell experiments to investigate illness at a large scale for future clinical trials.