Local cellular ource of apolipoprotein E in the human retina and retinal pigmented epithelium: implication for the proce of druen formation

PURPOE: The inheritance of pecific apolipoprotein E allelle ha been linked to atherocleroi, Alzheimer dieae, and, mot recently, to the incidence of age-related macular degeneration. Apolipoprotein E i a common component of the extracellular plaque and depoit characteritic of thee diorder, including druen, which are a hallmark of age-related macular degeneration. Accordingly, we aeed the potential bioynthetic contribution of local ocular cell type to the apolipoprotein E found in druen. METHOD: We meaured apolipoprotein E mRNA level in human donor tiue uing a quantitative aay of apolipoprotein E trancription, and we localized apolipoprotein E protein to pecific cell type and compartment in the neural retina, retinal pigmented epithelium, and choroid uing laer canning confocal immunofluorecence microcopy. REULT: Apolipoprotein E immunoreactivity i aociated with photoreceptor outer egment, the retinal ganglion cell layer, the retinal pigmented epithelium baal cytoplam and baal lamina, and with both collagenou layer of Bruch membrane. Apolipoprotein E appear to be a ubiquitou component of druen, irrepective of clinical phenotype. It alo accumulate in the cytoplam of a ubpopulation of retinal pigmented epithelial cell, many of which overlie or flank druen. Mean level of apolipoprotein E mRNA in the adult human retina are 45% and 150% of the level meaured in liver and adult brain, the two mot abundant bioynthetic ource of apolipoprotein E. Apolipoprotein E mRNA level are highet in the inner retina, and lowet in the outer retina where photoreceptor predominate. ignificant level of apolipoprotein E mRNA are alo preent in the retinal pigmented epithelium/choroid complex and in cultured human retinal pigmented epithelial cell. CONCLUION: Apolipoprotein E protein i trategically located at the ame anatomic locu where druen are ituated, and the retinal pigmented epithelium i the mot likely local bioynthetic ource of apolipoprotein E at that location. Age-related alteration of lipoprotein bioynthei and/or proceing at the level of the retinal pigmented epithelium and/or Bruch membrane may be a ignificant contributing factor in druen formation and age-related macular degeneration pathogenei.