Abstract
To study how APP is cleaved by BACE1 (β-secretase) and Presenilin1(γ-secretase) during development of mouse retina, we investigated the localizations of BACE1, Presenilin1, and their proteolytic products (APP-NT, APP-CT, and Aβ) at the times of postnatal 4, 7, 11 days and 12 wks immunohistochemically. BACE1 was localized in IPL together with APP-NT at P4 and P7, then not only in IPL but also in OPL at P11, and finally diffused across the retina at 12 wks. From P7 to 12 wks, APP-NT became distributed in the vitread processes of Muller cells. In contrast, both Presenilin1 and APP-CT showed the similar changes in distribution pattern that they were localized in IPL from P4 to P11 but diffused across the retina at 12 wks. Thus APP-NT and APP-CT were processed differently from each other from P7. Consistently with these findings, Aβ was distributed in IPL at P4 and P7 then not only in IPL but also in OPL at P11. Our surveys indicate that BACE1 cleaves APP during P7 and P11 and also suggest that Muller cells take APP-NT in their vitread processes. [Jpn J Physiol 54 Suppl:S161 (2004)]
