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Snapshots of Life: Lighting up the Promise of Retinal Gene Therapy

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mouse retina

Caption: Large-scale mosaic confocal micrograph showing expression of a marker gene (yellow) transferred by gene therapy techniques into the ganglion cells (blue) of a mouse retina.
Credit: Keunyoung Kim, Wonkyu Ju, and Mark Ellisman, National Center for Microscopy and Imaging Research, University of California, San Diego

The retina, like this one from a mouse that is flattened out and captured in a beautiful image, is a thin tissue that lines the back of the eye. Although only about the size of a postage stamp, the retina contains more than 100 distinct cell types that are organized into multiple information-processing layers. These layers work together to absorb light and translate it into electrical signals that stream via the optic nerve to the brain.

In people with inherited disorders in which the retina degenerates, an altered gene somewhere within this nexus of cells progressively robs them of their sight. This has led to a number of human clinical trials—with some encouraging progress being reported for at least one condition, Leber congenital amaurosis—that are transferring a normal version of the affected gene into retinal cells in hopes of restoring lost vision.

To better understand and improve this potential therapeutic strategy, researchers are gauging the efficiency of gene transfer into the retina via an imaging technique called large-scale mosaic confocal microscopy, which computationally assembles many small, high-resolution images in a way similar to Google Earth. In the example you see above, NIH-supported researchers Wonkyu Ju, Mark Ellisman, and their colleagues at the University of California, San Diego, engineered adeno-associated virus serotype 2 (AAV2) to deliver a dummy gene tagged with a fluorescent marker (yellow) into the ganglion cells (blue) of a mouse retina. Two months after AAV-mediated gene delivery, yellow had overlaid most of the blue, indicating the dummy gene had been selectively transferred into retinal ganglion cells at a high rate of efficiency [1].


Snapshots of Life: Seeing, from Eye to Brain

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Credit: Xueting Luo and Kevin Park, University of Miami

Fasten your seat belts! We’re going to fly through the brain of a mouse. Our tour guide is Kevin Park, an NIH-funded neuroscientist at the University of Miami, who has developed a unique method to visualize neurons in an intact brain. He’s going to give us a rare close-up of the retinal ganglion cells that carry information from the eye to the brain, where the light signals are decoded and translated.

To make this movie, Park has injected a fluorescent dye into the mouse eye; it is taken up by the retinal cells and traces out the nerve pathways from the optic nerve into the brain.


Guarding Against Glaucoma: What Can We Do?

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Chart showing the theoretical increase in the number of cases of Glaucoma, 2010-2050

Source: National Eye Institute, NIH

This graph provides a frightening look at a problem that could threaten the vision of more than 6 million Americans by 2050: glaucoma. Glaucoma is a group of diseases that damage the eye’s optic nerve — a bundle of 1 million-plus nerve fibers connecting the light-sensitive retina to the brain — and that can lead to vision loss and blindness.

NIH research is trying to change this picture by developing better strategies for treatment and prevention. But you can also help. How? By getting your eyes checked regularly.

With early detection and treatment, serious vision loss can often be prevented. Anyone can develop glaucoma, but some folks are at higher risk:

  • African Americans over age 40
  • Everyone over age 60, especially Mexican Americans
  • People with a family history of glaucoma

Glaucoma often has no symptoms until a lot of damage has already been done.  So the best way to prevent a bad outcome from glaucoma is by undergoing a simple eye exam that can be done by an ophthalmologist or an optometrist — at least once every 2 years for people in high-risk groups.

Source: National Eye Institute, NIH