Pigment dispersion syndrome is an eye condition in which the pigment from the iris is released within the eye and leads to elevated intraocular pressure and glaucoma in some patients. Pigment dispersion syndrome may afflict as many as 2.5%. Those with pigment dispersion syndrome are at high risk for developing a related form of glaucoma, pigmentary glaucoma.
There are several types of evidence that pigment dispersion syndrome and pigmentary glaucoma are caused at least in part by the actions of genes.
• Rare families have been reported in which pigment dispersion syndrome (and glaucoma) are passed down from generation to generation as a heritable trait.
• Also, pigment dispersion syndrome is more common in some races and ethnicities than in others, which suggests that heredity has a role in pigment dispersion syndrome.
• There are examples of animals in which pigment dispersion syndrome is transmitted as a heritable feature of the breed or strain, such DBA/2J mice.
These observations provide strong evidence that genes play a role in the development of pigment dispersion syndrome.
We are searching for genes that are involved in pigment dispersion syndrome using a variety of approaches.
First, we are exploring the role of genes that produce the pigment (melanin, Figure 1) that gets released in pigment dispersion syndrome. We are testing patients for disease-causing mutations in a panel of genes that are connected with production of melanin including the following genes:
• Tyrosinase-related protein 1 (TYRP1)
• Tyrosinase-related protein 2 (TYRP2)
• Glycoprotein (transmember) nmb (GPNMB)
• Catechol-O-methyltransferase (COMT)
We are also searching for genes that cause pigment dispersion syndrome by studying the inheritance of disease in large families that have many affected members (Figure 2). We are testing members of these families with tens of thousands of genetic markers. The pattern of inheritance of these genetic markers in the families will show us where the gene that causes the family’s eye disease lies within the genome. We have typed the families with the genetic markers and we are currently analyzing these data.
We are also searching for genetic risk factors for pigment dispersion syndrome with studies of large populations of patients and normal subjects. We have typed two cohorts of pigment dispersion syndrome patients and normal subjects at 500,000 genetic markers using Affymetrix DNA chips (Figure 3). We are currently analyzing these data and expect to search for pigment dispersion syndrome risk factors.
