New understanding of the occurrence of serious eye disease

6 December 2013

Our retina sends information to the brain about the environment in which we find ourselves. A number of eye diseases can be traced to genetic abnormalities, or mutations. One of those mutations results in a form of blindness that exists from birth or which occurs before the age of twenty. Research by the Netherlands Institute for Neuroscience has provided a new understanding of this disease. The research results are helping to develop a medicine to slow its  progression.

The findings of the group headed by Jan Wijnholds, Head of the Department of Neuromedical Genetics at the Netherlands Institute of Neuroscience, which is part of the Academy, have been published today in the prestigious journal PloS Genetics.

Wijnholds’ group was researching the origins of the disease, which is known in scientific circles as Leber congenital amaurosis (LCA) or retinis pigmentosa. Researchers were already aware that LCA patients suffer abnormalities in the development of the retina, but the cause was unknown. The research carried out by Wijnholds c.s. shows that as a result of mutations, these patients first acquire a thicker retina. This is followed by a decrease in the number of light-sensitive cells, which finally leads to blindness. As a result of this new understanding, the research team can focus on the development of a gene therapy medicine to slow the progression of this and other such eye diseases.

The role of CRUMBS or CRB proteins

Proteins are very important to our cells as they ensure the correct working of countless cell functions. CRB proteins play a vital role in the retina. They are responsible for the interaction between the light-sensitive cells (photoreceptor cells) and the glia cells, which protect and support the neurons. An improper functioning of CRB proteins often leads to proliferation: an unorganised structure of cell or tissue types. As a result of mutations in one of these CRB proteins, CRB1, LCA patients experience a thickening of the retina, which can easily be seen with a microscope.

New understanding

The research carried out by Jan Wijnholds c.s. demonstrates that the thickening in the retina occurs if, in addition to the CRB1 protein, the CRB2 protein is not functioning correctly either. The patient then experiences a temporary proliferation of various types of cells. This proliferation results in a thicker retina, following which the number of photoreceptor cells decreases, which results in blindness. This understanding makes it possible to explore new ways of slowing the development of these eye diseases.

Verdikt netvlies door disfunctionerende eiwitten. Foto: Lucie Pellissier, Nederlands Herseninstituut  Thickened retina resulting from dysfunctional proteins. Photo: Lucie Pellissier, Netherlands Institute for Neuroscience

About the Netherlands Institute for Neuroscience

logo_Herseninstituut.gifThe Netherlands Institute for Neuroscience conducts fundamental neuroscience research, with special emphasis on the brain and the visual system. Its research programme focuses on fundamental mechanisms, the causes of neurological and psychiatric disorders, the development of brain functions, and diagnostic and therapeutic strategies.