Spatial analysis of thickness changes in ten retinal layers of Alzheimer’s disease patients based on optical coherence tomography

Jáñez-Escalada, Luis; Jáñez-García, Lucía; Salobrar‐García, Elena; Santos-Mayo, Alejandro; Hoz, Rosa de; Yubero, Raquel; Gil, Pedro; Ramı́rez, José M.

doi:10.1038/s41598-019-49353-0

Cited by 36 publications

(49 citation statements)

References 66 publications

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“…Cell displacement and process reorientation towards an injury site are early features of microglial activation [44,45]. The microglial soma displacement towards the nuclear layers could explain the thickening in some areas of the retinal nuclear layers and the parallel thinning in plexiform layers observed by OCT using a new method for the segmentation of retinal layers in patients with mild AD [11,46]. In addition, it has been postulated that the vertical arrangement of microglial cells, like that of Müller cells, could assist in the distribution of signaling between different microglial plexuses to communicate to the rest of the retina where damage has occurred [6,47].…”

Section: Discussionmentioning

confidence: 99%

“…In AD patients, alterations in the retinal structure detected by Optical Coherence Tomography (OCT) have been reported, suggesting that these alterations could be useful as biomarkers [10][11][12]. According to these studies, in the retina of AD patients, as well as in human postmortem specimens, Aβ plaques have been found from the outer plexiform layer (OPL) to the nerve fiber layer (NFL) [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Microglial Activation in the Retina of a Triple-Transgenic Alzheimer’s Disease Mouse Model (3xTg-AD)

Salobrar‐García

Rodrigues‐Neves

Ramírez

et al. 2020

IJMS

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Alzheimer’s disease (AD) is the most common type of dementia in the world. The main biomarkers associated with AD are protein amyloid-β (Aβ) plaques and protein tau neurofibrillary tangles, which are responsible for brain neuroinflammation mediated by microglial cells. Increasing evidence has shown that the retina can also be affected in AD, presenting some molecular and cellular changes in the brain, such as microglia activation. However, there are only a few studies assessing such changes in the retinal microglia in animal models of AD. These studies use retinal sections, which have some limitations. In this study, we performed, for the first time in a triple-transgenic AD mouse model (3xTg-AD), a quantitative morphometric analysis of microglia activation (using the anti-Iba-1 antibody) in retinal whole-mounts, allowing visualization of the entire microglial cell, as well as its localization along the extension of the retina in different layers. Compared to age-matched animals, the retina of 3xTg-AD mice presents a higher number of microglial cells and a thicker microglial cell body area. Moreover, the microglia migrate, reorient, and retract their processes, changing their localization from a parallel to a perpendicular position relative to the retinal surface. These findings demonstrate clear microglia remodeling in the retina of 3xTg-AD mice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microglial Activation in the Retina of a Triple-Transgenic Alzheimer’s Disease Mouse Model (3xTg-AD)

Salobrar‐García

Rodrigues‐Neves

Ramírez

et al. 2020

IJMS

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“…Two photographs of each eye fundus were obtained using the non-mydriatic retinal camera Canon CR-DGi (Canon Inc., Tokyo, Japan). Optic nerve head (ONH) colorimetric evaluation determined the ONH Hb amount using the Laguna ONhE program, as described in previous studies [20,22,25]. The percentages of the amount of ONH Hb were quantified blindly and independently of the examiner, since the value is automatically provided by the Laguna ONhE program.…”

Section: Optic Nerve Head (Onh) Colorimetric Assessmentmentioning

confidence: 99%

“…Changes in optic nerve head (ONH) reflectance can detect variations in Hb levels, indirectly allowing the assessment of ONH perfusion [20,21]. Laguna ONhE is a program that allows the measurement of ONH perfusion, detecting the pallor caused by a decrease in capillary density and, consequently, axonal loss [22]. Several studies have shown its usefulness in both ocular [22][23][24][25][26] and cerebral [27,28] neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Ocular Vascular Changes in Mild Alzheimer’s Disease Patients: Foveal Avascular Zone, Choroidal Thickness, and ONH Hemoglobin Analysis

Salobrar‐García

Méndez-Hernández

Hoz

et al. 2020

JPM

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In Alzheimer’s disease (AD), vascular changes could be caused by amyloid beta (Aβ) aggregates replacing the contractile smooth musculature of the arteriole walls. These changes happen in the brain vascular network, but also in the eye, and are related to decreased vascular density and low blood flow. In patients with Alzheimer’s disease, thinning of the choroid and the retina has been shown. The aim of this prospective study was to assess the retinal and choroidal vascular systems, analyzing the choroidal thickness with optical coherence tomography (OCT), the foveal avascular zone (FAZ) with OCT-angiography (OCTA), and the optic nerve head (ONH) hemoglobin with the Laguna ONhE program, to evaluate which of the two ocular vascular systems shows earlier changes in mild AD patients. These patients, compared to controls, showed a significantly thinner choroid at all the analyzed points, with the exception of the temporal macula (at 1000 and 1500 µm from the fovea). On the other hand, the FAZ and ONH hemoglobin did not show significant differences. In conclusion, a thinner choroid was the main ocular vascular change observed in mild AD patients, while the retinal vessels were not yet affected. Therefore, choroidal thickness could be used an early biomarker in AD.

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“…[10] Microvascular changes of the DCP are complemented by the structural thinning of the inner nuclear layer thickness in AD individuals. [40] Changes in the DCP in AD individuals may present later in the disease stage, but a longitudinal study will be required to con rm this hypothesis.…”

Section: Dcp In Ad Individualsmentioning

confidence: 99%

Retinal Microvascular Alterations in Alzheimer’s Disease and Mild Cognitive Impairment

Chua

et al. 2020

Preprint

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Background: The retina and brain share many neuronal and vasculature characteristics developmentally and potential biomarkers may be present in the retina. We investigated the retinal microvasculature in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) using optical coherence tomography angiography (OCTA).Methods: In this cross-sectional study, 24 AD participants, 37 MCI participants, and 29 controls were diagnosed according to internationally accepted criteria. OCTA images of the superficial and deep capillary plexus (SCP, DCP) of the retinal microvasculature were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 with AngioPlex, Carl Zeiss Meditec, Dublin, CA). The main outcome measures were vessel density (VD) and fractal dimension (FD) in the SCP and DCP within a 2.5-mm ring around the fovea were compared between groups. Perfusion density of large vessels and foveal avascular zone (FAZ) area were additional outcome parameters.Results: Age, gender and race did not differ among groups. However, there was a significant difference in diabetes status (P=0.039), and systolic blood pressure (P=0.008) among the groups. After adjusting for confounders, AD participants showed significantly decreased VD in SCP and DCP (P = 0.005 and P = 0.016, respectively) and decreased FD in SCP (P = 0.008), compared to controls. MCI participants showed significantly decreased VD and FD only in SCP (P = 0.005 and P < 0.001, respectively) and not the DCP (P > 0.05) compared with controls. There was no difference in the OCTA variables between AD and MCI (P > 0.05). Perfusion density of large vessels and FAZ area did not differ significantly between groups (P > 0.05).Conclusions and relevance: Eyes of patients with AD have significantly reduced macular VD in both plexuses whereas MCI participants only showed reduction in the superficial plexus. Changes in the retinal microvasculature and capillary network may mirror small vessel cerebrovascular changes in AD.

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Spatial analysis of thickness changes in ten retinal layers of Alzheimer’s disease patients based on optical coherence tomography

Cited by 36 publications

References 66 publications

Microglial Activation in the Retina of a Triple-Transgenic Alzheimer’s Disease Mouse Model (3xTg-AD)

Microglial Activation in the Retina of a Triple-Transgenic Alzheimer’s Disease Mouse Model (3xTg-AD)

Ocular Vascular Changes in Mild Alzheimer’s Disease Patients: Foveal Avascular Zone, Choroidal Thickness, and ONH Hemoglobin Analysis

Retinal Microvascular Alterations in Alzheimer’s Disease and Mild Cognitive Impairment

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