OHSU scientists have published a paper that provides new information on retinal development and visual system abnormalities present in dystroglycanopathy, a form of muscular dystrophy that results from defective function of the protein dystroglycan.
Patients with severe forms of dystroglycanopathy frequently experience visual system problems in addition to other neurodevelopmental abnormalities. There is some understanding of dystroglycan’s influence on brain development, but its role in regulating retinal development has remained poorly understood. A team led by Kevin Wright, Ph.D., an assistant professor at the Vollum Institute, has published findings in the Journal of Neuroscience that provide new insight into the mechanisms of dystroglycan function in the retina using a mouse model of dystroglycanopathy.
Reena Clements, a neuroscience graduate student in the Wright lab, demonstrated that dystroglycan is required for maintaining the structural integrity of the inner limiting membrane in the developing retina. The team found that in the absence of functional dystroglycan, this membrane, which separates the retina from the vitreous, begins to degenerate. Breaches that form in the membrane allow neurons to migrate into the vitreous space, disrupting the highly organized structure of the retina.
These results demonstrate that disorganization of retinal circuit development is a likely contributor to visual dysfunction in patients with dystroglycanopathy. The findings in the eye are similar to what previously has been seen in the brain, suggesting a critical role for dystroglycan that is conserved throughout the developing nervous system.
In addition to Wright and Clements, coauthors include Rolf Turk, Ph.D., and Kevin P. Campbell, Ph.D.
This work was supported by the National Institutes of Health (R01-NS091027 (K.M.W.), the Whitehall Institute (K.M.W.), the Medical Research Foundation of Oregon (K.M.W.), the National Science Foundation Graduate Research Fellowship Program (R.C.), a LaCroute Neurobiology of Disease Fellowship (R.C.), a Tartar Trust Fellowship (R.C.), the National Institute of Neurological Disorders and Stroke (P30-NS061800 to the OHSU Advanced Light Microscopy Core), and the Paul D. Wellstone Muscular Dystrophy Cooperative Research Center (1U54NS053672 to K.P.C.).