Age-Related Alterations in the Retinal Microvasculature, Microcirculation, and Microstructure.
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ABSTRACT:
SUBMITTER: Wei Y
PROVIDER: S-EPMC5527847 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:PurposeBlood vessels of the retina provide an easily-accessible, representative window into the condition of microvasculature. We investigated how retinal vessel structure captured in fundus photographs changes with age, and how this may reflect features related to patient health, including blood pressure.ResultsWe used two approaches. In the first approach, we segmented the retinal vasculature from fundus photographs and then we correlated 25 parameterized aspects ("traits")-comprising 15 measures of tortuosity, 7 fractal ranges of self-similarity, and 3 measures of junction numbers-with participant age and blood pressure. In the second approach, we examined entire fundus photographs with a set of algorithmic CHARM features. We studied 2,280 Sardinians, ages 20-28, and an U.S. based population from the AREDS study in 1,178 participants, ages 59-84. Three traits (relating to tortuosity, vessel bifurcation number, and vessel endpoint number) showed significant changes with age in both cohorts, and one additional trait (relating to fractal number) showed a correlation in the Sardinian cohort only. When using second approach, we found significant correlations of particular CHARM features with age and blood pressure, which were stronger than those detected when using parameterized traits, reflecting a greater signal from the entire photographs than was captured in the segmented microvasculature.ConclusionsThese findings demonstrate that automated quantitative image analysis of fundus images can reveal general measures of patient health status.
| S-EPMC6497255 | biostudies-literature
Project description:Most studies examining associations between hypertension and brain white matter microstructure have focused on older adults or on cohorts with a large age range. Because hypertension effects on the brain may vary with age, it is important to focus on middle age, when hypertension becomes more prevalent. We used linear mixed-effect models to examine differences in white matter diffusion metrics as a function of hypertension in a well-characterized cohort of middle-aged men (n=316; mean, 61.8 years; range, 56.7-65.6). Diffusion metrics were examined in 9 tracts reported to be sensitive to hypertension in older adults. Relative to normotensive individuals, individuals with long-standing hypertension (>5.6 years) showed reduced fractional anisotropy or increased diffusivity in most tracts. Effects were stronger among carriers than among noncarriers of the apolipoprotein E ?4 allele for 2 tracts connecting frontal regions with other brain areas. Significant differences were observed even after adjustment for potentially related lifestyle and cardiovascular risk factors. Shorter duration of hypertension or better blood pressure control among hypertensive individuals did not lessen the adverse effects. These findings suggest that microstructural white matter alterations appear early in the course of hypertension and may persist despite adequate treatment. Although longitudinal studies are needed to confirm these findings, the results suggest that prevention-rather than management-of hypertension may be vital to preserving brain health in aging.
| S-EPMC4499000 | biostudies-literature
Project description:PurposeThis study aimed to explore the characteristics of retinal perfusion and its associations with high myopia.MethodsA total of 760 participants were included. Peripapillary radial peripapillary capillary perfusion, foveal avascular zone, and parafoveal perfusion were measured using optical coherence tomography angiography (OCTA). Tilted disc ratio and parapapillary atrophy were determined using swept-source optical coherence tomography.ResultsA total of 760 young healthy participants with myopic eyes were included in the analysis. The mean axial length and titled disc ratio were 26.43 ± 1.14 and 0.76 ± 0.08 mm in the high-myopia group and 24.79 ± 0.75 and 0.80 ± 0.09 mm in the control group, respectively. The high-myopia group exhibited significantly larger parapapillary atrophy, lower tilted disc ratio, lower radial peripapillary capillary vessel density, larger area of foveal avascular zone, and lower deep parafoveal vessel density. In the multivariate analysis, titled disc ratio significantly correlated with radial peripapillary capillary vessel density (P = 0.0134), larger foveal avascular zone (P = 0.0062), and lower deep parafoveal vessel density (P < 0.0001).ConclusionsReduced radial peripapillary capillary and deep parafoveal vessel density and enlarged area of foveal avascular zone were observed in high myopia. Tilted disc ratio correlated with retinal perfusion.
| S-EPMC7002767 | biostudies-literature
Project description:Cerebral white matter exhibits age-related degenerative changes during the course of normal aging, including decreases in axon density and alterations in axonal structure. Noninvasive approaches to measure these microstructural alterations throughout the lifespan would be invaluable for understanding the substrate and regional variability of age-related white matter degeneration. Recent advances in diffusion magnetic resonance imaging (MRI) have leveraged high gradient strengths to increase sensitivity toward axonal size and density in the living human brain. Here, we examined the relationship between age and indices of axon diameter and packing density using high-gradient strength diffusion MRI in 36 healthy adults (aged 22-72) in well-defined central white matter tracts in the brain. A recently validated method for inferring the effective axonal compartment size and packing density from diffusion MRI measurements acquired with 300 mT/m maximum gradient strength was applied to the in vivo human brain to obtain indices of axon diameter and density in the corpus callosum, its sub-regions, and adjacent anterior and posterior fibers in the forceps minor and forceps major. The relationships between the axonal metrics, corpus callosum area and regional gray matter volume were also explored. Results revealed a significant increase in axon diameter index with advancing age in the whole corpus callosum. Similar analyses in sub-regions of the corpus callosum showed that age-related alterations in axon diameter index and axon density were most pronounced in the genu of the corpus callosum and relatively absent in the splenium, in keeping with findings from previous histological studies. The significance of these correlations was mirrored in the forceps minor and forceps major, consistent with previously reported decreases in FA in the forceps minor but not in the forceps major with age. Alterations in the axonal imaging metrics paralleled decreases in corpus callosum area and regional gray matter volume with age. Among older adults, results from cognitive testing suggested an association between larger effective compartment size in the corpus callosum, particularly within the genu of the corpus callosum, and lower scores on the Montreal Cognitive Assessment, largely driven by deficits in short-term memory. The current study suggests that high-gradient diffusion MRI may be sensitive to the axonal substrate of age-related white matter degeneration reflected in traditional DTI metrics and provides further evidence for regionally selective alterations in white matter microstructure with advancing age.
| S-EPMC6467051 | biostudies-literature
Project description:PURPOSE:To assess which microstructural models best explain the diffusion-weighted MRI signal in the human placenta. METHODS:The placentas of nine healthy pregnant subjects were scanned with a multishell, multidirectional diffusion protocol at 3T. A range of multicompartment biophysical models were fit to the data, and ranked using the Bayesian information criterion. RESULTS:Anisotropic extensions to the intravoxel incoherent motion model, which consider the effect of coherent orientation in both microvascular structure and tissue microstructure, consistently had the lowest Bayesian information criterion values. Model parameter maps and model selection results were consistent with the physiology of the placenta and surrounding tissue. CONCLUSION:Anisotropic intravoxel incoherent motion models explain the placental diffusion signal better than apparent diffusion coefficient, intravoxel incoherent motion, and diffusion tensor models, in information theoretic terms, when using this protocol. Future work will aim to determine if model-derived parameters are sensitive to placental pathologies associated with disorders, such as fetal growth restriction and early-onset pre-eclampsia. Magn Reson Med 80:756-766, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
| S-EPMC5947291 | biostudies-literature
Project description:The nitric oxide-guanylyl cyclase-1-cyclic guanylate monophosphate (NO-GC-1-cGMP) pathway is integral to the control of vascular tone and morphology. Mice lacking the alpha catalytic domain of guanylate cyclase (GC1-/-) develop retinal ganglion cell (RGC) degeneration with age, with only modest fluctuations in intraocular pressure (IOP). Increasing the bioavailability of cGMP in GC1-/- mice prevents neurodegeneration independently of IOP, suggesting alternative mechanisms of retinal neurodegeneration. In continuation to these studies, we explored the hypothesis that dysfunctional cGMP signaling leads to changes in the neurovascular unit that may contribute to RGC degeneration. We assessed retinal vasculature and astrocyte morphology in young and aged GC1-/- and wild type mice. GC1-/- mice exhibit increased peripheral retinal vessel dilation and shorter retinal vessel branching with increasing age compared to Wt mice. Astrocyte cell morphology is aberrant, and glial fibrillary acidic protein (GFAP) density is increased in young and aged GC1-/- mice, with areas of dense astrocyte matting around blood vessels. Our results suggest that proper cGMP signaling is essential to retinal vessel morphology with increasing age. Vascular changed are preceded by alterations in astrocyte morphology which may together contribute to retinal neurodegeneration and loss of visual acuity observed in GC1-/- mice.
| S-EPMC8954518 | biostudies-literature
Project description:Purpose:The purpose of this study was to characterize the microstructure of the nonjuxtapapillary microvasculature dropout (MvD) in healthy myopic eyes. Methods:This cross-sectional study included 50 eyes (25 eyes with a nonjuxtapapillary MvD and 25 age-matched eyes without any MvD) from a cohort of 126 nonglaucomatous healthy myopic eyes having parapapillary atrophy (PPA) γ-zone. The parapapillary deep-layer microvasculature was evaluated in en-face images obtained using swept-source optical coherence tomography (OCT) angiography (OCTA). A nonjuxtapapillary MvD was defined as an area with focal absence of vascular signals in the distal portion of PPA confined to the nonjuxtapapillary area. Enhanced depth-imaging OCT scanning was performed to assess the parapapillary microstructure. Results:Nonjuxtapapillary MvD was found in 25 eyes (19.8%). The parapapillary microstructure at the nonjuxtapapillary MvD in 18 eyes was characterized by the misalignment of Bruch's membrane (BM)-retinal pigment epithelium (RPE) complex, which was identified by the absence of BM-RPE complex and the presence of the inner retina and sclera. In seven eyes with a nonjuxtapapillary MvD but without such misaligned BM-RPE complex, RPE atrophy was observed at the location of the nonjuxtapapillary MvD. Eyes with a nonjuxtapapillary MvD had a longer axial length (AXL; P = 0.013) and a wider γ-zone (P < 0.001) than age-matched control eyes without any MvD. Conclusions:The microstructure at the nonjuxtapapillary MvD in healthy myopic eyes was characterized in approximately 70% of eyes by temporally misaligned BM-RPE complex. Although the clinical importance of the nonjuxtapapillary MvD remains to be determined, it should be differentiated from the parapapillary choroidal MvD observed in glaucoma.
| S-EPMC7329630 | biostudies-literature
Project description:The first goal of the study was to find the genes that explain the difference in progression of age-related retinal degeneration (ageRD) between the inbred strains C57BL/6J-c2J (B6a) and BALB/cByJ (C). The specific goal was to find the candidate genes that explain the chromosome 6 and chromosome 10 quantitative trait loci (QTL) found in a previous study. Genes differentially expressed in retina between both strains and that map to the QTL are candidate genes. By integrating different approaches: microarray study, knowledge-based candidate gene search and screening of genetic variants, we found 35 candidate genes for chromosome 6 QTL and 14 candidate genes for chromosome 10 QTL. Five genes for each QTL were selected for sequencing and qPCR analysis. One gene, Tnfaip3 was selected for phenotypic testing and was excluded as the quantitative trait gene for chr10 QTL. The second goal of the study was to find biological processes and pathways associated with ageRD by Gene Ontology analysis of the microarray data. We concentrated on GO terms overrepresented in either strain at 8 months; the age when there is a difference in the phenotype (outer nuclear layer thickness). The GO analysis revealed that transcripts associated with inflammation, mitochondrial envelope, DNA repairing and oxidative stress were increased in the ageRD sensitive C strain with age (8 months). In the ageRD resistant B6a strain transcripts associated with antioxidant response, regulation of blood vessel size and growth factor activity were increased with age. Transcripts associated with cell remodeling and lipid metabolism were increased in either strain with age. This study aims to identify gene expression differences in posterior eyecups between the strains C and B6a at 4 months and at 8 months. Twelve animals were used per strain and time point for a total of 48 mice. Total RNA for 3 animals (6 eyes) were pooled giving a total of 4 biological replicates per strain and time point. The 4-month C samples labeled with Cy5 were hybridized with the 4-month B6a samples labeled with Cy3 (4 biological replicates); the 8-month C samples labeled with Cy5 were hybridized with the 8-month B6a samples labeled with Cy3, for 8 arrays (4 biological replicates). A second set of eight arrays were used to analyzed the same RNA samples but with the dye orientation reversed, yielding a total of 16 arrays in the experiment. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc.
2010-05-12 | E-GEOD-18151 | biostudies-arrayexpress
Project description:Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value?=?2.11×10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.
| S-EPMC3680438 | biostudies-literature
Project description:Optimal vascular function is vital for prevention of dementia. We hypothesized that elderly post-stroke survivors who preserve cognitive function show unperturbed cerebral microvasculature compared with those who develop dementia.Using stereological spherical probe software, we compared the length density (Lv, cumulative vessel length per unit tissue volume) of hippocampal microvessels in post mortem brain tissue from post-stroke survivors, Alzheimer's disease (AD), vascular dementia (VaD) and normal ageing control subjects. We also assessed microvessel diameters in the same subjects. Microvessels were identified by markers of endothelial cells (glucose transporter 1; GLUT1), basement membrane (collagen IV; COL4) and smooth muscle cell ?-actin (SMA).We found increased Lv of both GLUT1 and COL4 immunostained microvessels (P?<?0.05) in the hippocampal CA1 region of post-stroke demented (PSD) and AD cases compared with post-stroke nondemented (PSND), control and VaD subjects. However, no changes were apparent in the CA2 region. We also noted significant increase in Lv in the entorhinal cortex of AD compared with PSND and PSD subjects. The mean diameter of microvessels was decreased in PSD, compared with PSND, as well as in AD and VaD compared with controls. Cumulative frequency analysis showed PSND subjects to have significantly greater proportion of microvessels with diameters, ranging from 7 to 12??m.An increase in microvascular Lv in AD and PSD suggests either an increase in angiogenesis or the formation of newer microvessel loops in response to cerebral hypoperfusion. The decreased vessel diameters found in AD and VaD suggests increased vasoconstriction in dementia.
| S-EPMC4282329 | biostudies-other