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Progressive vision loss, and possibly blindness, are hallmarks of juvenile neuronal ceroid lipofuscinosis (JNCL) or CLN3-Batten disease. New research shows how the disease-associated mutation could potentially lead to degeneration of photoreceptor cells in the retina and subsequent vision loss.
“The importance and early onset of retinal degeneration in JNCL makes it likely that compromised cellular processes in JNCL are essential for the health and function of the retina,” said Ruchira Signh, Ph.D., professor associate in the Department of Ophthalmology and Center for Visual Science and lead author of the study published in the journal Communications biology. “It is important to understand how vision loss is triggered in this disease, what is primary and what is secondary, and this will allow us to develop new therapeutic strategies.”
Batten disease is caused by a mutation in the CLN3 gene, which is found on chromosome 16. Most children with JNCL have a missing part in the gene that inhibits the production of certain proteins. Rapidly progressive vision loss can begin in children as young as 4 years old and eventually develop learning and behavior problems, slow cognitive decline, seizures and loss of motor control. Most patients with the disease die between the ages of 15 and 30.
It has been well established that vision loss in JNCL is due to degeneration of light-sensitive tissue in the retina. Vision loss associated with JNCL can precede other neurological symptoms by several years in some cases, often leading to misdiagnoses in patients with other more common retinal degenerations. However, one of the barriers to studying vision loss in Batten disease is that mouse models of the CLN3 gene mutation do not produce the retinal degeneration or vision loss seen in humans. In addition, examination of eye tissue after death reveals extensive degeneration of retinal cells that does not allow researchers to understand the precise mechanisms that lead to vision loss.
URMC is a hub for Batten disease research. The medical center is home to the University of Rochester Batten Center (URBC), one of the country’s leading centers dedicated to the study and treatment of this disease. URBC is led by pediatric neurologist Jonathon Mink, MD, Ph.D., who is a co-author of the study. Batten disease is also one of the key research projects to be undertaken by the Center for Intellectual and Developmental Diseases Research at the University of Rochester, supported by the National Institute of Child Health and Human Development. .
To study Batten’s disease in the patient’s own cells, the research team redesigned skin cells from patients and unaffected family members to create human-induced pluripotent stem cells. These cells, in turn, were used to create retinal cells that possessed the CLN3 mutation. Using this new human cell model of the disease, the new study shows for the first time that proper functioning of CLN3 is necessary for the cellular structure of the retinal pigment epithelium, the cellular layer of the retina that nourishes photoreceptor cells. photoreceptors in the retina and is critical for their survival and function and therefore their vision.
Singh points out that understanding how RPE cell dysfunction contributes to the loss of photoreceptor cells in Batten disease is an important first step, and this will allow researchers to target a specific cell type in the eye for future help. gene therapies, cell transplants and drug interventions.
Source of the story:
Materials provided by University of Rochester Medical Center. Note: Content can be changed for style and length.
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