Techniques to Quantify cGMP Dysregulation as a Common Pathway Associated with Photoreceptor Cell Death in Retinitis Pigmentosa.

The targeted development of neuroprotective therapies for retinitis pigmentosa (RP) depends upon a better understanding of the mechanisms of photoreceptor cell death. Nucleotide metabolite-associated photoreceptor cell death is an emerging area of research that is important in multiple models of RP, yet the exact pathophysiology remains to be elucidated. One common pathway of photoreceptor cell death in RP is cGMP dysregulation, which is underscored by its potential to be relevant in up to 30% of patients with RP. Optimizing tools for detecting and quantifying nucleotide metabolites in the retina is vital to expanding this area of research. Immunohistochemistry is useful for localizing abnormally high levels of cGMP in a cell-specific manner, while enzyme-linked immunosorbent assay and liquid chromatography-mass spectrometry are quantitative and more sensitive. These techniques can form the basis for more sophisticated experiments to elucidate upstream events in photoreceptor cell death, which will hopefully lead to the development of novel therapies for patients with RP.