Our vision depends on a healthy retina, a thin layer of cells at the back of eye that sense light and send messages to the brain via the optic nerve and enable us to see.

In 2019, CERA Principal Investigator Dr Raymond Wong led a team of Australian researchers who developed the world’s most detailed retinal gene atlas.

The project, a collaboration between CERA, the University of Melbourne, the University of Queensland and the Garvan Institute of Medical Research, provided unprecedented insights into the genetic signals of retinal cells.

The group examined the complex genetic sequences behind more than 20 000 individual retinal cells. They then captured the precise genetic profile of each of the major cell types within the retina and the genes they ‘express’ to function normally.

“By creating this genetic map, we can better understand what enables cells to function and contribute to healthy vision, and what genetic signals cause a cell to stop functioning and lead to vision loss,” says Dr Wong. “It provides a ‘high resolution’ map of those molecular genetic signals happening within the cell.”

That project has accelerated research underway at CERA to develop new techniques to restore sight.

The loss of light-sensing photoreceptors in the retina can lead to irreversible blindness in diseases such as retinitis pigmentosa, age- related macular degeneration and diabetic retinopathy.

Now Dr Wong and his team are investigating ways to restore them using a technique known as cellular reprogramming.

Targeting the retina’s Müller glial cells, the team are hoping to ‘reprogram’ them by introducing genes which could turn them into photoreceptors.

Switching on genes

“We’re growing these cells in the lab, and switching on different sets of genes to see which are the best combinations to turn them into photoreceptors,’’ says Dr Wong.

A gene therapy could ultimately involve injecting reprogramming genes into the eye of the patient to regenerate new photoreceptors, says Dr Wong.

Dr Wong’s team is also exploring reprogramming Müller glia cells into retinal ganglion cells which make up the optic nerve that connects the retina to the brain. This work could help patients with diseases such as glaucoma and Leber’s Hereditary Optic Neuropathy (LHON).

The team is also using highly advanced techniques to understand how defective genes contribute to other retinal degenerative diseases, including age- related macular degeneration (AMD).

These techniques include induced pluripotent stem cells (IPS cells), CRISPR and transcriptomics.

With IPS cells, cells are grown from a person’s own skin or blood cells and ‘reprogrammed’ as a stem cell that can be turned into eye cells as a model to study AMD in the lab.

The team then uses the CRISPR technique to switch on and switch off multiple genes to test their function. Through transcriptomics, which is a readout of gene expression in a cell, the team can see what changes take place and understand how they contribute to AMD.

With research supported by the NHMRC grant, Retina Australia and the Kel & Rosie Day Foundation, Dr Wong and his team are hopeful their work will contribute to restoring people’s sight in the future.

“This funding gives us the opportunity to get ‘proof of concept’ and preclinical data on the efficacy of the technology.

“We’re very excited about this research,” he says. “It could potentially help more than 190 million people with vision impairment.”