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Sight fails when defective eye cells cripple renewal
Date:9/1/2011

age, until reaching blindness.

Genes connected to the disease have been known for some time. To find the molecular mechanism that causes sight loss, the researchers examined mouse models of the disease and 9 patients with the syndrome.

Optical imaging of the patients over a decade revealed an abnormal interface between the cones and the adjacent layer of tissue, called the retinal pigment epithelium.

Using gene-sequencing techniques on the mouse models, the team found expression of 30 genes involved in sight differed in healthy mice versus the disease models. Three of the genes were engaged in renewal of photoreceptors, a process called phagocytosis.

The researchers used a scanning electron microscope to produce images down to 100 nanometers, or the size of the largest holes in a surgical mask.

They found no phagosomes, essentially compartments made in cone cell membranes in which specialized cells called phagocytes of the retinal pigment epithelium eat cone material. In a healthy retina, phagosomes are present; phagocytes eat about 10 percent of the cone per day, continually renewing the cone.

The images instead showed bulbous cones in which metabolites that would normally be consumed remain, causing the swelling and turning toxic, the researchers said.

Analysis of cell cultures confirmed aberrations in the cones themselves were the cause of the problem, not the adjacent pigment layer as was previously thought.

"What we learn from this inherited human disease, and its mouse model, will be helpful to understand the aging process of the retina, like that seen in age-related macular degeneration," said Krzysztof Palczweski, John H. Hord Professor and chair of the Department of Pharmacology at CWRU School of Medicine. Palzcweski is Mustafi's advisor and senior author of the paper. "It is very likely that the phagocytotic process described in Debarshi's paper is a dysfunction as we age."

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Contact: Kevin Mayhood
kevin.mayhood@case.edu
216-368-4442
Case Western Reserve University
Source:Eurekalert

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