PMID- 18791173 OWN - NLM STAT- MEDLINE DCOM- 20090206 LR - 20220330 IS - 1552-5783 (Electronic) IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 50 IP - 2 DP - 2009 Feb TI - Beta-amyloid deposition and functional impairment in the retina of the APPswe/PS1DeltaE9 transgenic mouse model of Alzheimer's disease. PG - 793-800 LID - 10.1167/iovs.08-2384 [doi] AB - PURPOSE: To determine whether beta-amyloid (Abeta) deposition affects the structure and function of the retina of the APPswe/PS1DeltaE9 transgenic (tg) mouse model of Alzheimer's disease. METHODS: Retinas from 12- to 19-month old APPswe/PS1DeltaE9 tg and age-matched non-transgenic (ntg) littermates were single or double stained with thioflavine-S and antibodies against Abeta, glial fibrillar acidic protein (GFAP), microglial marker F4/80, choline acetyltransferase (ChAT), and syntaxin 1. Quantification of thioflavine-S positive plaques and retinal layer thickness was analyzed semi-quantitatively, whereas microglial cell size and levels of F4/80 immunoreactivity were evaluated using a densitometry program. Scotopic electroretinogram (ERG) recording was used to investigate retinal physiology in these mice. RESULTS: Thioflavine-S positive plaques appeared at 12 months in the retinas of APPswe/PS1DeltaE9 tg mice with the majority of plaques in the outer and inner plexiform layers. Plaques were embedded in the inner plexiform layer strata displaying syntaxin 1 and ChAT. The number and size of the plaques in the retina increased with age. Plaques appeared earlier and in greater numbers in females than in male tg littermate mice. Microglial activity was significantly increased in the retinas of APPswe/PS1DeltaE9 tg mice. Although we did not detect neuronal degeneration in the retina, ERG recordings revealed a significant reduction in the amplitudes of a- and b-waves in aged APPswe/PS1DeltaE9 tg compared to ntg littermates. CONCLUSIONS: The present findings suggest that Abeta deposition disrupts retinal structure and may contribute to the visual deficits seen in aged APPswe/PS1DeltaE9 tg mice. Whether Abeta is involved in other forms of age-related retinal dysfunction is unclear. FAU - Perez, Sylvia E AU - Perez SE AD - Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. FAU - Lumayag, Stephen AU - Lumayag S FAU - Kovacs, Beatrix AU - Kovacs B FAU - Mufson, Elliott J AU - Mufson EJ FAU - Xu, Shunbin AU - Xu S LA - eng GR - P01 AG014449/AG/NIA NIH HHS/United States GR - R01 AG010668/AG/NIA NIH HHS/United States GR - R01 AG043375/AG/NIA NIH HHS/United States GR - AG10668/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080912 PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Antigens, Differentiation) RN - 0 (Benzothiazoles) RN - 0 (Fluorescent Dyes) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Presenilin-1) RN - 0 (Syntaxin 1) RN - 0 (Thiazoles) RN - 0 (monocyte-macrophage differentiation antigen) RN - 2390-54-7 (thioflavin T) RN - EC 2.3.1.6 (Choline O-Acetyltransferase) SB - IM MH - Aging/physiology MH - Alzheimer Disease/genetics/*metabolism/physiopathology MH - Amyloid beta-Peptides/*metabolism MH - Amyloid beta-Protein Precursor/genetics MH - Animals MH - Antigens, Differentiation/metabolism MH - Benzothiazoles MH - Choline O-Acetyltransferase/metabolism MH - *Disease Models, Animal MH - Electroretinography MH - Female MH - Fluorescent Antibody Technique, Indirect MH - Fluorescent Dyes/metabolism MH - Glial Fibrillary Acidic Protein/metabolism MH - Gliosis/*metabolism/physiopathology MH - Male MH - Mice MH - Mice, Transgenic MH - Microscopy, Confocal MH - Presenilin-1/genetics MH - Retina/physiopathology MH - Retinal Diseases/*metabolism/*physiopathology MH - Syntaxin 1/metabolism MH - Thiazoles/metabolism PMC - PMC3697019 MID - NIHMS477992 EDAT- 2008/09/16 09:00 MHDA- 2009/02/07 09:00 PMCR- 2013/07/01 CRDT- 2008/09/16 09:00 PHST- 2008/09/16 09:00 [pubmed] PHST- 2009/02/07 09:00 [medline] PHST- 2008/09/16 09:00 [entrez] PHST- 2013/07/01 00:00 [pmc-release] AID - iovs.08-2384 [pii] AID - 10.1167/iovs.08-2384 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2009 Feb;50(2):793-800. doi: 10.1167/iovs.08-2384. Epub 2008 Sep 12.