title: Ocular changes in TgF344-AD rat model of Alzheimer's disease.
abstract: OBJECTIVE
  Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed.
  
  
  METHODS
  Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response and luminance threshold recording from the superior colliculus. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques.
  
  
  RESULTS
  As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature.
  
  
  CONCLUSIONS
  In this study, we observed pathological changes in the choroid and in RPE cells in the TgF344-AD rat model; choroidal thinning was observed further in human AD retina. Along with Ab deposition, the inflammatory response was manifested by microglial recruitment and complement activation. Further studies are needed to elucidate the significance and mechanisms of these pathological changes [corrected].
authors.affiliation: Cedars-Sinai Regenerative Medicine Institute, Los Angeles, California.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Tsai
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Ljubimov
authors.forename: Sergey
authors.initials: S
authors.lastname: Girman
authors.forename: Fred N
authors.initials: FN
authors.lastname: Ross-Cisneros
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Sadun
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cohen
authors.forename: Shaomei
authors.initials: S
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002829:Choroid / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051381:Rats; D011916:Rats, Inbred F344; D012164:Retinal Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D014792:Visual Acuity
chemical_list: D000682:Amyloid
keywords: Alzheimer disease; choroidal thickness; retinal pigment epithelium; visual acuity