Age-related macular degeneration's incurable diagnosis and therapy are getting closer now that new genetic markers for the condition have been identified.
The research is published in the journal Nature Communications.
Researchers from the University of Melbourne, the Menzies Institute for Medical Research at the University of Tasmania, the Garvan Institute of Medical Research, and the Center for Eye Research Australia reprogrammed stem cells to produce models of diseased eye cells. They then examined DNA, RNA, and proteins to identify the genetic hints.
"We've tested the way that differences in people's genes impact the cells involved in age-related macular degeneration. At the smallest scale we've narrowed down specific types of cells to pinpoint the genetic markers of this disease," says joint lead author Professor Joseph Powell, Pillar Director of Cellular Science at Garvan. "This is the basis of precision medicine, where we can then look at what therapeutics might be most effective for a person's genetic profile of disease."
Age-related macular degeneration, often known as AMD, is the gradual degradation of the macular, a part of the retina that is in the center and toward the rear of the eye, which may impair or cause loss of central vision. About 15% of Australians over the age of 80 have vision loss or blindness, while one in seven Australians over the age of 50 are affected.
Although the underlying causes of the decline are yet unknown, environmental and genetic variables play a part. Age, family history, and smoking are risk factors.
Researchers collected skin samples from 79 patients, both with and without geographic atrophy, the late stage of AMD. Their skin cells were altered to transform back into stem cells known as induced pluripotent stem cells, which were then directed by molecular cues to become retinal pigment epithelium cells, which are the cells impacted by AMD.
The retina's back is lined with cells called retinal pigment epithelium, which are crucial to the retina's health and functionality. The loss of vision in AMD is brought on by the degeneration of photoreceptors, which are light-sensing neurons in the retina that transmit visual information to the brain.
439 molecular fingerprints linked to AMD were discovered by analysis of 127,600 cells, with 43 of those being potential new gene variants.
Key pathways that were identified were subsequently tested within the cells and revealed differences in the energy-making mitochondria between healthy and AMD cells, rendering mitochondrial proteins as potential targets to halt or reverse the progression of AMD.
Furthermore, the molecular signatures can now be used for screening of treatments using patient-specific cells in a dish.
"Ultimately, we are interested in matching the genetic profile of a patient to the best drug for that patient. We need to test how they work in cells relevant to the disease," says co-lead of the study Professor Alice Pébay, from the University of Melbourne.
In order to better understand the underlying genetic causes of complex human diseases, Professor Powell and co-lead authors Professor Pébay, Professor Alex Hewitt, and the Menzies Institute for Medical Research in Tasmania and the Center for Eye Research Australia have been working together for many years.
"We have been building a program of research where we're interested in stem cell studies to model disease at very large scale to do screening for future clinical trials," says Professor Hewitt.
In another recent study, the researchers uncovered genetic signatures of glaucoma—a degenerative eye disease causing blindness—using stem cell models of the retina and optic nerve.
The genetic origins of Parkinson's and cardiovascular disorders are other areas where researchers are focusing their attention.