Altered expression of secreted frizzled-related protein-2 in retinitis pigmentosa retinas

PURPOSE. Inherited retinal degenerations such as retinitis pigmentosa (RP) are characterized by progressive death of the photoreceptors due to apoptos is. To identify changes in gene expression associated with the degenerative state in RP retinas, expression profiling of apoptosis-related genes was p erformed using a gridded array technique. METHODS. Total RNAs from RP and control retinas were used to generate radio labeled cDNA probes to screen gridded membrane arrays of 205 apoptosis-rela ted genes. Reverse transcription-polymerase chain reaction was used to gene rate probes corresponding to differentially expressed genes for Northern bl ot analysis and for mRNA in situ hybridization studies of retinal, cryosect ions. Fluorescence immunocytochemistry was performed on retinal sections us ing available antibodies. RESULTS. By expression profiling, we identified upregulated expression of t he mRNA for secreted Frizzled-related protein-2 (SFRP2) in RP retina in com parison with control. By Northern blot analysis, SFRP2 mRNA levels were 2- to 20-fold higher in RP samples than in controls. The localization of SFRP2 mRNA by in situ hybridization varied according to The degree of degenerati on, from stratified in relatively well-preserved retinas to diffuse in the highly degenerative state. By immunofluorescence, SFRP2 protein in RP retin as was found mainly to colocalize with the cell adhesion and signal transdu cing protein beta-catenin. CONCLUSIONS. SFRPS can regulate apoptosis in vitro and appear to interact w ith the Wnt/Frizzled signaling pathway, which includes routes to apoptotic activation. Increased SFRP2 expression in RP retinas suggests that an alter ed pattern of Wnt signal transduction may be a step in the degenerative pro cess linking causal mutations with eventual photoreceptor demise.