Glaucoma

The term glaucoma describes a heterogeneous group of disorders and is the second most prevalent cause of bilateral blindness in the western world. Although single cases represent the majority of glaucoma patients, heredity is high. Positive family history is an important risk factor, along with age and elevated intraocular pressure. Reports of aggregation of primary open-angle glaucoma sometimes segregating as a Mendelian trait have long suggested heritability in glaucoma. The prevalence of primary open-angle glaucoma, which represents the most abundant form of glaucoma, has been documented to be 7-10 times higher than that of the general population (Wolfs et al, 1998). Some forms of glaucoma, like congenital glaucoma or juvenile glaucoma are associated with mutations in specific genes but the situation is more complex with the chronic glaucoma of older patients. Linkage analysis has led to the identification of at least nine different glaucoma loci and four corresponding genes (MYOC, CYP1B1, OPTN and WDR36; Stone et al, 1997; Stoilov et al, 1997; Rezaie et al, 2002; Monemi et al, 2005). The impact of these genes majority of non-familial glaucoma cases is not clear yet. Specific mutations in monogenic cases can only be found in 2-7% of patients in unselected cohorts (e.g. Aldred et al, 2004). It is not kwown how many genes contribute to the disorder and how they eventually interact with each other. Obviously there are a number of genes that lead to glaucoma in case they harbour mutations. On the patients with specific mutations in glaucoma-associated genes will necessarily develop any symptoms. Glaucoma pathogenesis seems to be multifactorial with significant genetic and environmental contributions. Defining the genetic basis of hereditary forms of glaucoma is an important step towards a presymptomatic screening of people at risk and will help understanding the underlying pathogenic mechanisms.
Our archive of DNA samples comprises more than 250 clinically well defined glaucoma patients that have been examined clinically and genetically as well. We have established screening protocols for several glaucoma related genes (MYOC, CYP1B1, OPTN, FOXC1, PITX2) and could identify a range of specific mutations in all of them. We focus especially on the recruitment of extended glaucoma pedigrees as they are a prerequisite for phenotype-genotype correlation studies. In addition, the project deals with identifying risk factors for normal tension glaucoma as well as the functional characterization of optineurin, which is associated with apotosis of retinal ganglion cells, as it occurs in glaucoma.