Causes of incurable blindness
Age–related macular degeneration (AMD) is a progressive retinal disease leading to irreversible vision loss. About one in seven Australians over the age of 50 has AMD and about 15% of people over the age of 80 suffer from visual impairment or blindness. The main causes of AMD remain unknown, but genetic and environmental factors play a role. Risk factors include age, family history, and smoking.
A research team from the Garvan Institute of Medical Research, the University of Melbourne, the Menzies Institute of Medical Research at the University of Tasmania and the Australian Eye Research Center reprogrammed stem cells to create models of affected human retinal cells, and then analyzed DNA, RNA and proteins to pinpoint the genetic signs of AMD. They tested how differences in genes affect the cells involved in the death of retinal photoreceptors and narrowed down the range of specific cell types to pinpoint the genetic markers of this disease. This is necessary for the further search for treatment methods that will be most effective for the genetic profile of the disease of a particular patient.
The researchers took skin samples from 79 volunteers with and without late-stage AMD (geographical atrophy). The skin fibroblasts were reprogrammed to make them induced pluripotent stem cells, and then, using molecular signals, they were transformed into retinal pigment epithelial cells – cells that are the first to be damaged in AMD.
Pigment epithelial cells are the outer layer of the retina, necessary for the health and normal functioning of nerve cells. Their degeneration leads to the death of photoreceptors – light-sensitive neurons in the retina that transmit visual signals to the brain and are responsible for vision loss in AMD.
Analysis of 127,600 cells revealed 439 molecular features associated with AMD, with 43 of them being potential new gene variants. The pathways found were subsequently tested inside cells: they indicated differences in mitochondria between healthy cells and cells from AMD patients, which makes mitochondrial proteins potential targets for preventing or altering the course of AMD.
Molecular features can also be used to find patient-specific treatments.
The authors continue to collaborate and are currently developing a research program that will use stem cells to simulate diseases on a very large scale in order to screen potential AMD treatments for future clinical trials.
The work is not limited to AMD. In another recent study using similar models, the team found genetic signs of glaucoma, a degenerative eye disease that causes irreversible blindness. The researchers also intend to determine the genetic causes of Parkinson's disease and cardiovascular diseases.
Article by A.Senabouth et al. Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Garvan Institute: Genetic clues to age-related macular degeneration revealed.