BioProject

The retinal degeneration slow gene (rds/peripherin), is essential for normal photoreceptor (rods and cones) outer segment structure in the neurosensory retina. More...

The retinal degeneration slow gene (rds/peripherin), is essential for normal photoreceptor (rods and cones) outer segment structure in the neurosensory retina. Our rds animal model, are stable transgenic mice that carry a null mutation (complete lost of function) in the rds gene. Those animals become blind, mimicking a human form of retinitis pigmentosa. In our experience we have observed dramatic levels of photoreceptor rescue after subretinal injection of those animals with a ciliary neurotrophic factor (CNTF) inserted into a recombinant Adeno-associate virus (rAAV) vector. However, this cell rescue is accompanied by changes in photoreceptor nuclear morphology, attenaution of the electroretinogram and evetually Apoptosis. By using Microarray analysis we hope to identify genes whose expression or lack thereof brings the cell to the brink of suicide. Identification of these genes will suggest therapeutic targets for the future. We will determine gene expression patterns in the retina of rds mice non-injected and injected with CNTF/rAAV virus after 60 days of injection. Our working hypothesis is that the injected CNTF/rAAV vector induces the expression of genes that somehow partially restores the photoreceptor morphology of rds mice. Paradoxically, it also has a negative effect on the phisiology of these cells (ERG). The up or down regulation of genes in different areas of the neurosensory retina collected by Laser Capture Microdissection will give us an insight on the relevance of candidate genes responsible for this phenomenon. We will use rds mice at age P25 and inject their rigth eye with CNTF/AVV virus (2.68x e13 particles/ml) and use the left eye as a control. Injection is performed via subretinal. Retinas will be collected at age P90 post injection. RNA will be extracted and processed accordingly for MIcroarray analysis. Keywords: dose response Less...