Cataracts are a common eye condition and a leading cause of vision loss – but they don’t all form the same way.

While many develop with age, others can arise from inflammation, steroid medication or eye surgery.

Now, a new CERA study has looked at which genes are behaving abnormally in different types of cataracts in a step towards targeted therapies – and perhaps even ways to prevent cataracts altogether.

In a world first, researchers compared the active genes of people experiencing four different types of cataracts:

• age-related cataracts
• uveitic cataracts (from eye inflammation)
• steroid-induced cataracts, and
• post-vitrectomy cataracts (after eye surgery).

The researchers collected tiny samples of lens cells from 89 patients undergoing routine cataract surgery at several Melbourne hospitals. The samples were transferred to the Australian Genome Research Facility for sequencing.

Honours student Dr Carrie Fei, who led the research with Dr Michael Dong, said it was the first project that directly compared gene activity across the four types of cataracts in humans.

The study was published in the journal Investigative Ophthalmology & Visual Science.

Dr Fei is now in her first year as an intern at The Alfred while Dr Dong is a first-year ophthalmology registrar at the Royal Victorian Eye and Ear Hospital.

Their supervisors were Associate Professor Anthony Hall from the Alfred Hospital and CERA’s Head of Uveitis and Retinal Vascular Disease Research, and Chief Medical Officer, of Cerulea Clinical Trials, Professor Lyndell Lim.

“Human cataracts have been very difficult to reliably study as we do not have a reliable animal model,” Dr Fei says.

“Being able to look directly at the human lens and extract genes is relatively new.

“This is the first study that we know of that has really done it in these types of secondary cataract.”

In samples of cataracts caused by eye inflammation, the study found increased activity in genes linked to inflammation and cell death.

One such gene, C3, plays a key role in the body’s immune response and has been linked to eye diseases.

Other genes were also more active and are involved in stress and inflammation pathways.

The steroid-induced cataract samples showed changes in genes involved in cell growth and repair.

Dr Fei said the findings supported a theory that cataracts from steroid use may result from disruptions in the eye’s natural balance of growth factors.

The team also examined cataracts that developed after vitrectomy, a type of eye surgery.

During this, surgeons may use silicone oil to help keep the retina in position during healing.

The study showed that when silicone oil was used and later removed, thousands of genes were being differentially expressed compared to normal age-related cataracts.

Dr Fei and the research team found an innovative solution to analyse their massive dataset.

“Our main goal was to work out the differences but also to notice anything in common between age-related cataracts and the others,” she says.

“We ended with a huge list of genes that were significant – and the challenge of deciding on which genes to focus.”

When Dr Fei explained the problem to her software engineer partner, he helped write a code that automatically matched each gene to specified keywords in a vast collection of biomedical literature to find how many other papers had studied those specific genes.

“This saved me days of manual labour,” Dr Fei says.

“It’s a small section of the paper but arguably the most important because then we could triage the genes that seemed to be noteworthy in the existing literature.”

The CERA team acknowledged several limitations in the study.

They were not able to collect cells from deeper or more disease-affected regions of the lens where many cataracts form, nor did they have access to healthy lens tissue for comparison.

The use of a particular blue dye during surgery also slightly altered gene activity.

She says that the findings do not prove the identified genes are directly responsible for cataracts – but they do provide valuable leads.

“This project has created a significant pool of data for other researchers to build upon,” Dr Fei says.

“Understanding the different pathways that lead to cataract formation could one day help in developing targeted treatments or even stopping them before they form.”

Read the research

Fei C, Dong MR, Byars S, Shah JS, Hall AJ, Lim LL. RNA-Seq Study of Human Lens Epithelial Cells: Differentially Expressed Genes and Pathways in Steroid, Uveitic, Post-Vitrectomy, and Senile Cataracts. Invest Ophthalmol Vis Sci. 2025 May 1;66(5):4. doi: 10.1167/iovs.66.5.4