Elucidation of the genetic causes of retinal detachment

Abstract

Rhegmatogenous retinal detachment (RRD) is caused by a break in the neurosensory retina of the eye, thereby allowing fluid from the vitreous space into the space between the sensory retina and the retinal pigment epithelium. Untreated, this disorder can lead to blindness. A case-control study in relatives of RRD patients and healthy individuals showed that 8.24 per 100,000 individuals per year in the Netherlands present with RRD, and that familial occurrence of RRD is an independent risk factor, especially in families with more than two affected first degree relatives in two generations. Furthermore, two large families with autosomal dominant RRDs were studied. Affected individuals showed a lower average age of onset in comparison to sporadic RRD cases. Fellow eyes were more often affected, and rather than by the characteristic horseshoe tears in sporadic RRD, the RRDs in these families were predominantly caused by round, atrophic holes. Poor surgical results were found, and because of proliferative vitreoretinopathy, multiple operations were often needed to reattach the retina. These results point out the necessity of timely recognition, and -if possible- prevention. Linkage analysis, performed to find the defective gene(s) involved in these families, showed significant LOD scores for both families in the region containing the COL2A1 gene, but a mutation in this gene was found in only one of them. To investigate the role of the COL2A1 gene in the development of RRD, 12 smaller families with RRD were studied. Three families showed cosegregation of the chromosomal region around the gene, but mutations in the gene were excluded in at least two of the three families, indicating that the COL2A1 gene is not the major affected gene in smaller families. In the remaining families showing cosegregation, another gene in the1 gene might be involved.