Correction appended: This article incorrectly stated that 506 sequences were observed to be associated with retinitis pigmentosa. It should have said that 506 sequences were observed that are not necessarily associated with retinitis pigmentosa. This article also incorrectly stated that the microarray is embedded with gene patterns. It should have said that the microarray is embedded with specific gene sequences.

Angela Cesere
Diagram shows the genetic patterns of retinitis pigmentosa the microarray can detect. (Courtesy of Kellogg Eye Center)

Embedded with DNA molecules that can screen through thousands of genetic sequences, microarrays have recently allowed University researchers to diagnose an eye disease that once took several years to detect.

In a study published in the September issue of Investigative Ophthalmology and Visual Science, a team of researchers lead by ophthalmology Prof. Rhada Ayyagari at the University’s Kellogg Eye Center successfully tested microarray technology’s ability to diagnose a specific type of retinitis pigmentosa, also known as RP.

With the new technology, ophthalmology Prof. John Heckenlively said, patients with the ocular disease can receive more precise diagnoses that will make treatment much easier.

RP causes progressive retinal degeneration that can lead to blindness. It is passed down and affects one out of 3,500 individuals worldwide according to the Kellogg Eye Center. Currently, the clinical diagnosis of RP is largely based on an individual’s electrical activity in the eye, loss of peripheral vision, night blindness and retinal changes. But Ayyagari said the symptoms of RP overlap with those of many other ocular disorders, making it challenging to provide a definite diagnosis.

While a clinical diagnosis is only the first step, molecular testing is needed to identify the gene and the mutations involved that cause the disorder.

Since there are more than 90 different genetic forms of RP and many forms look alike, manual sequencing techniques to detect the disease are very time consuming and inefficient.

Rather than rely on arduous diagnosing processes, Ayyagari and her team aimed to devise a new technique to detect the disease by directly analyzing the DNA of an individual with a microarray.

With a microarray, the DNA of a patient can be screened against multiple genes on a single platform, instead of the traditional sequencing of one gene at a time.

There are many different genetic patterns that can indicate the presence of RP. As result, the team used a microarray to siphon through the genetic patterns.

Microarrays work by measuring changes in gene expression patterns by comparing one gene pattern with another. A normal microarray would not be effective in a disease like RP because of the vast number of mutations that can indicate the disease.

However, Ayyagari and her team employed a microarray embedded with the specific gene sequences to detect RP among the hundreds of different variations found within genes.

Heckenlively at the Kellogg Eye Center examined the patients who participated in the study.

Thirty-five RP patients were screened using the microarray containing 11 genes known to cause RP. The sequences of the genes and mutations the researchers obtained were 99 percent accurate. At the same time, 506 sequence changes were detected but not necessarily associated with retinitis pigmentosa, and 120 of them were not previously reported.

Ayyagari said this result emphasizes the usefulness of the technique since it not only provides a definite diagnosis, but also deepens the understanding of the disorder on a molecular level.

“We’re excited about finding mutations in different genes that would modify other genes,” she said.

But there are still drawbacks to the technique: interpretation of the results is time consuming. Researchers expect to increase the number of genes that can be included on the microarray chips to make the technique more effective.

Still, the use of DNA screening chips is likely to become even more useful in the future because treatments currently under development to treat RP will be effective at treating people with the specific genetic mutations.

“That in turn means that when we have treatments, we would be better able to tell who is eligible for the treatment. It is basically speeding up the treatment process” Heckenlively said.

The Kellogg Eye Center is one of the leading centers for RP research and was among the first centers to set up a certified molecular diagnostics unit for retinal degenerations and glaucoma.

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