Purpose To investigate relationships between blood pressure and the thickness of single retinal layers in the macula. Methods Participants of the population-based Beijing Eye Study, free of retinal or optic nerve disease, underwent medical and ophthalmological examinations including optical coherence tomographic examination of the macula. Applying a multiple-surface segmentation solution, we automatically segmented the retina into its various layers. Results The study included 2237 participants (mean age 61.8±8.4 years, range 50–93 years). Mean thicknesses of the retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer, inner nuclear layer (INL), outer plexiform layer, outer nuclear layer/external limiting membrane, ellipsoid zone, photoreceptor outer segments (POS) and retinal pigment epithelium–Bruch membrane were 31.1±2.3 µm, 39.7±3.5 µm, 38.4±3.3 µm, 34.8±2.0 µm, 28.1±3.0 µm, 79.2±7.3 µm, 22.9±0.6 µm, 19.2±3.3 µm and 20.7±1.4 µm, respectively. In multivariable analysis, higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) were associated with thinner GCL and thicker INL, after adjusting for age, sex and axial length (all p<0.0056). Higher SBP was additionally associated with thinner POS and higher DBP with thinner RNFL. For an elevation of SBP/DBP by 10 mm Hg, the RNFL, GCL, INL and POS changed by 2.0, 3.0, 1.5 and 2.0 µm, respectively. Conclusions Thickness of RNFL, GCL and POS was inversely and INL thickness was positively associated with higher blood pressure, while the thickness of the other retinal layers was not significantly correlated with blood pressure. The findings may be helpful for refinement of the morphometric detection of retinal diseases.
more »
« less
A multi-scale/multi-physics model for the theoretical study of the vascular configuration of retinal capillary plexuses based on OCTA data
Abstract The retinal tissue is highly metabolically active and is responsible for translating the visual stimuli into electrical signals to be delivered to the brain. A complex vascular structure ensures an adequate supply of blood and oxygen, which is essential for the function and survival of the retinal tissue. To date, a complete understanding of the configuration of the retinal vascular structures is still lacking. Optical coherence tomography angiography has made available a huge amount of imaging data regarding the main retinal capillary plexuses, namely the superficial capillary plexuses (SCP), intermediate capillary plexuses (ICP) and deep capillary plexuses (DCP). However, the interpretation of these data is still controversial. In particular, the question of whether the three capillary plexuses are connected in series or in parallel remains a matter of debate. In this work, we address this question by utilizing a multi-scale/multi-physics mathematical model to quantify the impact of the two hypothesized vascular configurations on retinal hemodynamics and oxygenation. The response to central retinal vein occlusion (CRVO) and intraocular pressure (IOP) elevation is also simulated depending on whether the capillary plexuses are connected in series or in parallel. The simulation results show the following: (i) in the in series configuration, the plexuses exhibit a differential response, with DCP and ICP experiencing larger pressure drops than SCP; and (ii) in the in parallel configuration, the blood flow redistributes uniformly in the three plexuses. The different vascular configurations show different responses also in terms of oxygen profiles: (i) in the in series configuration, the outer nuclear layer, outer plexiform layer and inner nuclear layer (INL) are those most affected by CRVO and IOP elevation; and (ii) in the in parallel configuration the INL and ganglion cell layer are those most affected. The in series results are consistent with studies on paracentral acute middle maculopathy, secondary to CRVO and with studies on IOP elevation, in which DCP and ICP and the retinal tissues surrounding them are those most affected by ischemia. These findings seem to suggest that the in series configuration better describes the physiology of the vascular retinal capillary network in health and disease.
more »
« less
- NSF-PAR ID:
- 10327418
- Date Published:
- Journal Name:
- Mathematical Medicine and Biology: A Journal of the IMA
- Volume:
- 39
- Issue:
- 1
- ISSN:
- 1477-8599
- Page Range / eLocation ID:
- 77 to 104
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
more » « less
The mammalian CNS is capable of tolerating chronic hypoxia, but cell type-specific responses to this stress have not been systematically characterized. In the Norrin KO (
Ndp KO ) mouse, a model of familial exudative vitreoretinopathy (FEVR), developmental hypovascularization of the retina produces chronic hypoxia of inner nuclear-layer (INL) neurons and Muller glia. We used single-cell RNA sequencing, untargeted metabolomics, and metabolite labeling from13C-glucose to compare WT andNdp KO retinas. InNdp KO retinas, we observe gene expression responses consistent with hypoxia in Muller glia and retinal neurons, and we find a metabolic shift that combines reduced flux through the TCA cycle with increased synthesis of serine, glycine, and glutathione. We also used single-cell RNA sequencing to compare the responses of individual cell types inNdp KO retinas with those in the hypoxic cerebral cortex of mice that were housed for 1 week in a reduced oxygen environment (7.5% oxygen). In the hypoxic cerebral cortex, glial transcriptome responses most closely resemble the response of Muller glia in theNdp KO retina. In both retina and brain, vascular endothelial cells activate a previously dormant tip cell gene expression program, which likely underlies the adaptive neoangiogenic response to chronic hypoxia. These analyses of retina and brain transcriptomes at single-cell resolution reveal both shared and cell type-specific changes in gene expression in response to chronic hypoxia, implying both shared and distinct cell type-specific physiologic responses. -
Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling. While the principal mechanisms of blood flow regulation after neuronal firing are generally known, mechanistic hemodynamic simulations cannot yet pinpoint the exact spatial and temporal coordination between the network of arteries, arterioles, capillaries and veins for the entire brain. Because of the potential significance of blood flow and oxygen supply simulations for illuminating spatiotemporal regulation inside the cortical microanatomy, there is a need to create mathematical models of the entire cerebral circulation with realistic anatomical detail. Our hypothesis is that an anatomically accurate reconstruction of the cerebrocirculatory architecture will inform about possible regulatory mechanisms of the neurovascular interface. In this article, we introduce large-scale networks of the murine cerebral circulation spanning the Circle of Willis, main cerebral arteries connected to the pial network down to the microcirculation in the capillary bed. Several multiscale models were generated from state-of-the-art neuroimaging data. Using a vascular network construction algorithm, the entire circulation of the middle cerebral artery was synthesized. Blood flow simulations indicate a consistent trend of higher hematocrit in deeper cortical layers, while surface layers with shorter vascular path lengths seem to carry comparatively lower red blood cell (RBC) concentrations. Moreover, the variability of RBC flux decreases with cortical depth. These results support the notion that plasma skimming serves a self-regulating function for maintaining uniform oxygen perfusion to neurons irrespective of their location in the blood supply hierarchy. Our computations also demonstrate the practicality of simulating blood flow for large portions of the mouse brain with existing computer resources. The efficient simulation of blood flow throughout the entire middle cerebral artery (MCA) territory is a promising milestone towards the final aim of predicting blood flow patterns for the entire brain.more » « less
-
Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.more » « less
-
Impaired blood flow and oxygenation contribute to many ocular pathologies, including glaucoma. Here, a mathematical model is presented that combines an image-based heterogeneous representation of retinal arterioles with a compartmental description of capillaries and venules. The arteriolar model of the human retina is extrapolated from a previous mouse model based on confocal microscopy images. Every terminal arteriole is connected in series to compartments for capillaries and venules, yielding a hybrid model for predicting blood flow and oxygenation throughout the retinal microcirculation. A metabolic wall signal is calculated in each vessel according to blood and tissue oxygen levels. As expected, a higher average metabolic signal is generated in pathways with a lower average oxygen level. The model also predicts a wide range of metabolic signals dependent on oxygen levels and specific network location. For example, for high oxygen demand, a threefold range in metabolic signal is predicted despite nearly identical PO2 levels. This whole-network approach, including a spatially nonuniform structure, is needed to describe the metabolic status of the retina. This model provides the geometric and hemodynamic framework necessary to predict ocular blood flow regulation and will ultimately facilitate early detection and treatment of ischemic and metabolic disorders of the eye.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/imammb/dqab018
