Expression in the mammalian retina of parkin and UCH-L1, two components of the ubiquitin-proteasome system

The ubiquitin-proteasome system (UPS) functions as a major degradation pathway for misfolded and damaged proteins with an important neuroprotective role in the CNS against a variety of cellular stresses. Parkin and ubiquitin C-terminal hydrolase L1 (UCH-L1) are two relevant components of the UPS associated with a number of neurodegenerative disorders. We here address the expression profile of parkin and UCH-L1 in the mammalian retina, with special emphasis on primates. We describe for the first time the presence of parkin in the retina of mammals, including humans. Parkin and UCH-L1 genes were expressed at the mRNA and protein levels in the retina of all species examined. The immunolocalization pattern of parkin was quite widespread, being expressed by most retinal neuronal types, including photoreceptors. UCH-L1 was localized to horizontal cells and specific subtypes of bipolar and amacrine cells, as well as to ganglion cells and their axons forming the nerve fiber layer. In rodents no UCH-L1 immunoreactivity was found in cone or rod photoreceptors, whereas this protein was present along the whole length of cones in all other mammals. Remarkably, UCH-L1 was expressed by dopaminergic amacrine cells of primates. The ample distribution of parkin and UCH-L1 in the mammalian retina, together with the crucial role played by the UPS in normal neuronal physiology in the brain, points to a participation of these two proteins in the ubiquitin-proteasomal pathway of protein degradation in most retinal cell types, where they could exert a protective function against neuronal stress.

Research highlights
► Parkin and UCH-L1 mRNAs and proteins are expressed in the retina of mammals.
► Parkin distribution is widespread among retinal neurons, including photoreceptors.
► UCH-L1 localizes to specific subtypes of neurons, excluding cones in rodents.
► UCH-L1 is expressed by dopaminergic amacrine cells of primates.
► Parkin and UCH-L1 could have a role in the UPS and neuroprotection in the retina.