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NIH Research Matters

April 4, 2011

Eye Development Error Causes Cataracts, Glaucoma

Researchers have found a common mutation in patients with pediatric cataracts that could broaden our understanding of how the eye develops.

Photo of an eye.

A cataract is a clouding of the eye lens—the transparent tissue that focuses light onto the retina at the back of the eye, where images are recorded. The lens is made mostly of water and protein arranged to keep the tissue clear and let light pass through. If the proteins begin to clump together, they can form a cataract that clouds an area of the lens. This can happen as we age, but about 1 in every 30,000 babies nationwide develops cataracts because of mutations in their genetic code. Cataracts can be removed surgically, but for infants this procedure increases their risk of developing another eye disease, glaucoma.

In the new study, 2 research groups—led by Dr. Simon John from Jackson Laboratory in Bar Harbor, Maine, and Dr. Richard L. Maas of Brigham and Women's Hospital and Harvard Medical School in Boston—found that a few human patients and a strain of mice shared a malfunctioning gene, called TDRD7, that led to juvenile cataracts. The research, which was funded partly by NIH's National Eye Institute (NEI), National Institute for Child Health and Human Development (NICHD) and National Institute for General Medical Sciences (NIGMS), helped to uncover how lens development is regulated. The findings appeared in the March 25, 2011, issue of Science.

TDRD7 codes for a protein found in protein-RNA complexes called RNA granules. In a process called transcription, DNA sequences in genes are copied into more transient form as RNA. These "messenger RNAs" (mRNAs) can be modified, stored or degraded before being brought to the molecular machinery that translates the sequences into proteins. RNA granules regulate mRNAs after they are transcribed.

To characterize the role of TDRD7 in lens development, the researchers studied mice and chicks in which the TDRD7 gene was experimentally suppressed. They discovered that expression of TDRD7 is normally high in the developing lens. When TDRD7 was removed, the expression of genes important for eye development was significantly changed. In mice with experimentally suppressed TDRD7, cataracts formed within weeks of birth. These animals also began to develop glaucoma as they aged.

A process called oxidative stress has been previously suggested to contribute to glaucoma by damaging drainage structures in the eyes. The researchers demonstrated that TDRD7 mutations led to a dramatic reduction in stress granules—a specific type of RNA granule that helps protect against environmental stresses like oxidation.

"This means that mutations in the TDRD7 gene could cause a double jeopardy for childhood glaucoma," John explains. "First, they cause cataract, and cataract extraction may raise oxidative stress in the ocular drainage tissues. Second, they impair the formation of protective stress granules in response to oxidative stress."

Taken together, this research shows that TDRD7-containing RNA granules are crucial for normal lens function. The findings are one of the first examples of a posttranscriptional regulation mechanism for organ development, opening up a whole new field of investigation.

—by Amy Alabaster

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Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.

NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.

This page last reviewed on December 3, 2012

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