We are also testing the effects on IOP of mutating specific candidate genes. These genes are candidates to affect IOP based on their known functions. One of our interests is a family of genes that encode the natriuretic peptides. The elevated IOP and glaucoma are caused by pigment dispersion and iris atrophy resulting in blockage of aqueous humor drainage. Mice homozygous for D2 alleles at only one of these loci develop late-onset iris abnormalities, whereas mice homozygous for D2 alleles at both loci develop an earlier, more severe iris disease that is associated with a more severe glaucoma.
Current efforts focus on identifying the specific disease-causing genes.
This work is in collaboration with colleagues at the Jackson Laboratory and elsewhere. Mutant genes that affect various cellular processes are being bred into the glaucomatous strain to test the ability of these genes to modify the presence, onset, or severity of the glaucoma. For example, there is evidence supporting a role of the processes of apoptotic and excitotoxic cell death in glaucoma. Altered genes that block specific apoptotic or excitotoxic pathways are being tested for their effects on glaucoma in D2 mice. These studies will shed light on the relative importance of specific mechanisms of cell death in glaucoma and on whether these genes are likely to modify the presence, onset, or severity of glaucoma in people.