Effects of age and retinal degeneration on the expression of proprotein convertases in the visual cortex

Proprotein convertases (PCs) comprise a large family of subtilisin-like, eukaryotic, serine endoproteases that process substrates important in the development, homeostasis, and pathology of the nervous system. Despite important interactions with these substrates, including neurotrophins, PC expression throughout normal postnatal development and disease progression in the brain remains unknown. The primary objective of this study was to determine whether the expression profiles of widely expressed and tissue-specific PCs varied during normal brain development or neurological disorders. We examined the expression of mRNAs for seven PCs in the visual cortex of normal and visually impaired mice at 10 postnatal developmental time points between Week 1 and Week 35. Widely expressed PCs (furin, PACE4, PC5, and PC7) all exhibited a similar expression profile. High mRNA levels were seen at Week 1 with levels generally lower over the next 5-6 weeks. In visually impaired mice, widely expressed PCs again all exhibited a similar expression profile, but it was dramatically different than observed in normal mice. The temporal expression of tissue-specific PCs varied in wild-type mice. Interestingly, this variability was sharply reduced in visually impaired mice. Overall, these data suggest a timetable of altered PC expression that corresponds closely with the formation of functional visual maps in the visual cortex. The implications of these findings are discussed in the context of neurotrophin processing and synaptogenesis in the developing visual cortex.