Abstract
Purpose :
To evaluate changes in the production of beta amyloid peptides and the expression of the enzymes involved in the production of these peptides in the following areas; visual cortex, optic nerve and retina in healthy aging (C57/BL6 mice, 4 months old versus 18 Months old) and wild type mice versus AD triple transgenic mice (3xTg-AD).
Methods :
Double IF assays on coronary slides (10µm) of visual cortex, retina and optic nerve of young mice (4M) and old mice (25M), as well as wild type mice (4M) and 18M of 3xTg-AD were performed. Monoclonal antibodies for each one of the enzymes involved were used ; non amyloidogenic (alfa-secretase); ADAM10, ADAM9; Amyloidogenic pathway; BACE, Preseniline2 (PRES2) (The principal enzyme involved in ßA42 peptide production). Finally, to verify the expression changes of these enzymes, qRT-PCR assays for each enzyme were performed using mRNA of the same anatomic regions of the animals used.
Results :
There is an significant expression increase of the enzymes, BACE, ADAM 9, PRES2 and a reduction of ADAM 10 in retina, O.N. and VC on aged mice as well as on 3xTg-AD mice.
Conclusions :
1) These models are useful to study the production of amyloid beta in these anatomical areas in aging and in Alzheimer s disease. 2) The increase of the enzymes involved in the amyloidogenic pathway in the retina, O.N. and VC, suggest that ßA42 accumulation on these regions is a consequence of the over activation of this pathway in normal aging and Alzheimer s Disease. 3) These changes could be associated to the visual loss function observed in AD patients.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.