P2–212: Morphometric analysis of the retina in a triple‐transgenic model of Alzheimer's disease
Year: 2013
Type: article
Abstract: Reduction of retinal thickness has been reported in patients with mild cognitive impairment and Alzheimer's disease (AD). Recent studies reported Aβ accumulation, increase of TUNEL positive apoptotic bodies in the retinal ganglion cell (RGC) layer. However, morphometric analysis of RGC number and thickness of inner nuclear layer (INL) has not been characterized. We hypothesize that these two parameters can be served as biomarker to monitor degeneration in the retina of AD pathogenesis. Therefore, we aim to examine these two parameters in the retina of triple transgenic (3xTg) mice. Eyes from 10, 16 and 24-month-old 3xTg mice harboring PS1 M146V, APP Swe and tau P301L transgenes were compared with eyes from age matched wild-type C57 background controls. Paraffin r etinal sections with intact optic nerve were stained by hematoxylin and eosin for measurements of INL thickness and number of RGC in a double-blinded manner by using StereoInvestigator ®. β-Amyloid (Aβ) peptide was detected by Congo red staining and immunohistochemical analysis of 4G8 and C-terminal Aβ42 antibody. Apoptotic makers such as cleaved caspase-3 and TUNEL immunoreactivity were also examined. Starting from 10 months of age, there were significant decrease in the mean thickness of INL (37% loss) and the average number of RGCs (49.4% loss) in the 3xTg mice when compared with age-matched wild-type control. Aging of the 3xTg mice did not further affect the remaining cell number. In 3xTg mice, there was no Congo red positive staining in all the time points but 4G8 was detectable in the cell body of RGC and the cells in INL. Aβ42 was detectable in the retinal capillaries since 10 months. TUNEL and cleaved caspase-3 immunoreactive positive cells were also found in the RGC and INL. The retina of 3xTg mice can be used as a window of AD brain. Mutant gene triggered neuronal loss in the inner retina (both the RGC and INL) indicated that t his system can be used as an evaluation platform for drug intervention on AD progression in vivo.
Source: Alzheimer s & Dementia
Authors: Kin Chiu, Sara Mo‐Ching Leung, Irene Yan ‐Pui Leung, Carmen Ka‐Ming Lok, Raymond Turner, Yasuji Matsuoka, Kwok‐Fai So, Raymond Chuen‐Chung Chang
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2147430056