Australian scientists have developed the world’s most detailed gene map of the human retina, providing new and unprecedented insights into the underlying determinants of retinal cell function.
In a study that could provide the basis for future retinal disease therapies, Dr Raymond Wong, from the Centre for Eye Research Australia (CERA) and University of Melbourne, has led a team of researchers to produce the gene atlas that was recently published in the European Molecular Biological Organisation journal.
It is the first part of the eye to be mapped as part of the Human Cell Atlas Project, a global initiative to create reference maps of all human cells in order to better understand, diagnose and treat disease. It is also the first time an Australian group has contributed to the project.
Using eyes from three donors, Wong joined Dr Samuel Lukowski, from the Institute for Molecular Bioscience at the University of Queensland, and Associate Professor Joseph Powell, from the Sydney-based Garvan Institute of Medical Research, to examine the complex genetic sequences behind more than 20,000 individual cells. They developed a profile of all major cell types in the retina and the genes they express to function normally.
Using unsupervised clustering analysis, the team identified 18 transcriptionally distinct cell populations representing all known neural retinal cells. Cells mapped include rod and cone photoreceptors, retinal ganglion cells, and other cells that support the function and stability of the retina.
“By creating a genetic map of the human retina, we can understand the factors that enable cells to keep functioning and contribute to healthy vision,’’ Wong said. “It can also help us understand the genetic signals that cause a cell to stop functioning, leading to vision loss and blindness.’’
Powell said the retinal cell atlas would benefit researchers investigating inherited retinal diseases, which occur when “genetic mistakes” cause retinal cells to stop functioning.
“More than 200 genes are known to be associated with retinal diseases and having a detailed gene profile of individual retinal cell types, will help us study how those genes impact on different kinds of cells,” he said.
“This understanding is the first step to better identifying what causes disease and ultimately developing treatments.’’
Wong added that the atlas would assist scientists conducting research into cell therapy involving the use of pluripotent stem cells.
“The retinal cell atlas will give scientists a clear benchmark to assess the quality of the cells derived from st cells to determine whether they have the correct genetic code which will enable them to function.’’
Lukowski said the research offered “extraordinary potential”. Building on this atlas of health cells, future work could involve cells from other retinal diseases and across different stages of human development to provide useful tools for disease prediction.
Wong, Lukowski and Powell are part of the ANZ Human Eye Cell Atlas Consortium, a group of scientists from 20 partnering institutes and universities across Australia and New Zealand creating reference maps for different parts of the human eye.
Main Image: CERA’s Dr Raymond Wong, who led the research team to develop the retinal gene map. Image: Anna Carlile