Unique Disease Signatures
Rapidly entering the microRNA playing field are strategies to identify altered expression of microRNAs associated with hereditary diseases such as retinitis pigmentosa (RP), the most common form of inherited retinal degenerations. The eye disorder is characterized by progressive photoreceptor-cell death.
According to Arpad Palfi, Ph.D., post-doctoral fellow in the laboratory of G. Jane Farrar, Ph.D., at Trinity College, they generated a microRNA-expression profile in the mouse retina using microRNA microarray technology and real-time RT-PCR.
“Initially, we analyzed a transgenic mouse model in which the gene for rhodopsin has a specific mutation resulting in an RP phenotype,” Dr. Palfi explains. Rhodopsin is a retinal pigment responsible for light detection in rod photoreceptors. Following normalization to wild-type mice, we found an altered microRNA-expression profile involving several microRNAs (e.g., miR-1, -96, -133, and -183) in the rhodopsin-mutant transgenic mice. This data suggested that the normal microRNA expression profile is altered in the disease state.”
The group decided to expand on those studies by examining other RP mouse models. “We examined three RP mouse models using the same strategies and found a common signature in which levels of microRNAs-96, -182, and -183 were decreased while expression of microRNA-1, -133, and -142 were upregulated.”
The group will next examine what protein targets and pathways in the retina are affected by these altered microRNA expression patterns. “If we can understand how microRNAs work in normal and degenerating retinas, perhaps we can use microRNAs as a therapeutic tool, possibly in conjunction with other therapies, to beneficially influence outcome of RP.”