Um melhor diagnóstico e tratamento da degeneração macular relacionada à idade pode ocorrer no futuro após um novo avanço genético.
A descoberta de assinaturas moleculares de degeneração macular relacionada à idade ajudará no melhor diagnóstico e tratamento dessa doença ocular progressiva.
Graças à descoberta de novas assinaturas genéticas de degeneração macular relacionada à idade, um melhor diagnóstico e tratamento da doença ocular incurável está um passo mais próximo.
Cientistas do Garvan Institute of Medical Research, da Universidade de Melbourne, do Menzies Institute for Medical Research da Universidade da Tasmânia e do Center for Eye Research Australia, reprogramaram células-tronco para criar modelos de células oculares doentes e, em seguida, analisaram[{” attribute=””>DNA, RNA and proteins to pinpoint the genetic clues.
“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.”
A degeneração macular relacionada à idade, ou AMD, é a deterioração progressiva da macular – uma região no centro da retina e na parte de trás do olho – levando a um possível comprometimento ou perda da visão central. Cerca de um em cada sete australianos com mais de 50 anos é afetado e cerca de 15% das pessoas com mais de 80 anos têm perda de visão ou cegueira.
As causas subjacentes da deterioração permanecem elusivas, mas fatores genéticos e ambientais contribuem. Os fatores de risco incluem idade, histórico familiar e tabagismo.
A pesquisa é publicada hoje (26 de julho de 2022) na revista 
Black and white electron microscopy imaging of retinal pigment epithelium cells. Credit: Dr. Grace Lidgerwood
The researchers took skin samples from 79 participants with and without the late stage of AMD, called geographic atrophy. Their skin cells were reprogrammed to revert to stem cells called induced pluripotent stem cells, and then guided with molecular signals to become retinal pigment epithelium cells, which are the cells affected in AMD.
Retinal pigment epithelium cells line the back of the retina and are essential to the health and functioning of the retina. Their degeneration is associated with the death of photoreceptors, which are light-sensing neurons in the retina that transmit visual signals to the brain and are responsible for the loss of vision in AMD.
Fluorescent imaging of retinal pigment epithelium. Dr. Grace Lidgerwood
Analysis of 127,600 cells revealed 439 molecular signatures associated with AMD, 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 prevent or alter the course of AMD.
Further, 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.
Professor Powell and co-lead authors Professor Pébay, and Professor Alex Hewitt from the Menzies Institute for Medical Research in Tasmania and the Centre for Eye Research Australia, have a long-running collaboration to investigate the underlying genetic causes of complex human diseases.
“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 researchers are also turning their attention to the genetic causes of Parkinson’s and cardiovascular diseases.
Reference: “Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration” 26 July 2022, Nature Communications.
DOI: 10.1038/s41467-022-31707-4
This research was supported by the Macular Disease Foundation Australia, the Ophthalmic Research Institute of Australia, Retina Australia, the DHB Foundation, The Goodridge Foundation, the NHMRC, the ARC and the Medical Research Future Fund.
Professor Joseph Powell is Pillar Director of Cellular Science, Garvan Institute of Medical Research and Conjoint Deputy Director of Cellular Genomics Futures Institute, University of New South Wales
Professor Alice Pébay is a Principal Research Fellow at the Department of Anatomy and Physiology, and at the Department of Surgery, The University of Melbourne
Professor Alex Hewitt is an ophthalmologist and Research Fellow at the Menzies Institute for Medical Research at the University of Tasmania, and Head of Clinical Genetics at the Centre for Eye Research Australia.
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