The effects of the apoE4 genotype on the developing mouse retina

Maharshak, Idit; Salomon-Zimri, Shiran; Antes, Ran; Liraz, Ori; Nisgav, Yael; Livnat, Tami; Weinberger, Dov; Colton, Carol A.; Solomon, Arieh S.; Michaelson, Daniel M.

doi:10.1016/j.exer.2015.11.001

Cited by 8 publications

(12 citation statements)

References 48 publications

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“…Many of these findings mirror those recorded in AD patients (Table 3) [5, 6, 30, 39, 48, 52, 56, 72, 117, 123, 139, 148, 152, 154, 178, 184]. …”

Section: Non-specific Ocular Abnormalities In Animal Models Of Adsupporting

confidence: 72%

“…Double nuclei and hypertrophy in RPE; increased ATP q release; Mitochondrial swelling, crista fragmentation and reduced complexity[75, 151, 152, 178, 184]RatTgF344-ADMouseApoE4Choroid. Increased neovascularization post-LDI r , decreased VEGF s , damage to neonatal vascular branching[6, 123] a Drosophila expressing amyloid β-protein precursor b Drosophila expressing β-secretase 1 c Model expressing drosophila presenilin-1 protein d Glass multiple reporter drosophila model expressing Aβ 42 e Drosophila expressing AβPP-like protein f Drosophila model expressing human Aβ 42 g Mouse overexpressing APP isoform 695 bearing Swedish double mutations K670 M/N671L h Mouse overexpressing APP SWE /PS1 ΔE9 or APP SWE /PS1 M146L i Mouse overexpressing APP SWE/FL/LON /PS1 M146L/L286V j Drosophila model expressing human AβPP k Mouse overexpressing APP SWE /PS1/TAU P301L l Apoliprotein E mouse model m Monocyte chemoattractant protein-1 n Astrocytes positive for glial fibrillary acidic protein o APP SWE /PS1 ΔE9 rat model p Octodon degus , WT rodent native to Chile showing symptoms of sporadic AD q Adenosine triphosphate, in APP SWE /PS1 ΔE9 model overexpressing ATP r Laser-driven injury s Vascular endothelial growth factor …”

Section: Non-specific Ocular Abnormalities In Animal Models Of Admentioning

confidence: 99%

“…Structural changes in the retinas of AD animal models have included tight junction attenuation, variations in vascular branching and budding, and decreases in complexity, field area, and length of RGC dendrites (Table 3) [5, 6, 123, 148, 184]. While synaptic density in the Tg2576 mouse has shown no change in either pre- or post-synaptic markers [184], synaptic loss and impairment, typically related to cognitive deficits when observed in the brain, have been reported in the ApoE4 mouse retina [5, 6].…”

Section: Non-specific Ocular Abnormalities In Animal Models Of Admentioning

confidence: 99%

“…In addition, two studies investigating ocular changes in the ApoE4 mouse reported increased neovascularization following laser-driven injury and decreased VEGF levels in the choroid [6, 123]. Overall, the above studies, predominantly those pertaining to genetic murine models of AD, indicate that the effects of Alzheimer’s known to afflict the brain, especially synaptic loss and neuronal degeneration, also manifest in the retina.…”

Section: Non-specific Ocular Abnormalities In Animal Models Of Admentioning

confidence: 99%

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Ocular indicators of Alzheimer’s: exploring disease in the retina

et al. 2016

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Although historically perceived as a disorder confined to the brain, our understanding of Alzheimer’s disease (AD) has expanded to include extra-cerebral manifestation, with mounting evidence of abnormalities in the eye. Among ocular tissues, the retina, a developmental outgrowth of the brain, is marked by an array of pathologies in patients suffering from AD, including nerve fiber layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. While the hallmark pathological signs of AD, amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) comprising hyperphosphorylated tau (pTau) protein, have long been described in the brain, identification of these characteristic biomarkers in the retina has only recently been reported. In particular, Aβ deposits were discovered in post-mortem retinas of advanced and early stage cases of AD, in stark contrast to non-AD controls. Subsequent studies have reported elevated Aβ42/40 peptides, morphologically diverse Aβ plaques, and pTau in the retina. In line with the above findings, animal model studies have reported retinal Aβ deposits and tauopathy, often correlated with local inflammation, retinal ganglion cell degeneration, and functional deficits. This review highlights the converging evidence that AD manifests in the eye, especially in the retina, which can be imaged directly and non-invasively. Visual dysfunction in AD patients, traditionally attributed to well-documented cerebral pathology, can now be reexamined as a direct outcome of retinal abnormalities. As we continue to study the disease in the brain, the emerging field of ocular AD warrants further investigation of how the retina may faithfully reflect the neurological disease. Indeed, detection of retinal AD pathology, particularly the early presenting amyloid biomarkers, using advanced high-resolution imaging techniques may allow large-scale screening and monitoring of at-risk populations.

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“…Many of these findings mirror those recorded in AD patients (Table 3) [5, 6, 30, 39, 48, 52, 56, 72, 117, 123, 139, 148, 152, 154, 178, 184]. …”

Section: Non-specific Ocular Abnormalities In Animal Models Of Adsupporting

confidence: 72%

Section: Non-specific Ocular Abnormalities In Animal Models Of Admentioning

confidence: 99%

Section: Non-specific Ocular Abnormalities In Animal Models Of Admentioning

confidence: 99%

Section: Non-specific Ocular Abnormalities In Animal Models Of Admentioning

confidence: 99%

See 2 more Smart Citations

Ocular indicators of Alzheimer’s: exploring disease in the retina

et al. 2016

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“…24 It has been reported that the VEGF level is significantly and positively correlated with the ApoE levels in the retina and choroid of murine eyes and also in the human brain. [24][25][26][27] Because VEGF has been shown to be associated with neovascularization, these findings suggest that ApoE may be related to retinal neovascularization. However, the effects of the ApoEs (e.g., ApoE2, ApoE3, and ApoE4) on retinal neovascularization have not been fully investigated.…”

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confidence: 92%