Decreased Vascular Patterning in the Retinas of Astronaut Crew Members as New Measure of Ocular Damage in Spaceflight-Associated Neuro-ocular Syndrome

Vyas, Ruchi J.; Young, Millennia; Murray, Matthew C.; Predovic, Marina; Lim, Soyeoun; Jacobs, Nicole; Mason, Sara S.; Zanello, Susana B.; Taibbi, Giovanni; Vizzeri, Gianmarco; Parsons‐Wingerter, Patricia

doi:10.1167/iovs.61.14.34

Cited by 18 publications

(20 citation statements)

References 44 publications

(47 reference statements)

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“…The output consists of specialized vascular maps, spreadsheets of numerical results, and a log documenting the analysis. Vascular output parameters include vessel diameter ( D v ), vessel tortuosity ( T v ), vessel area density ( A v ), vessel length density ( L v ), vessel number density ( N v ), vessel branch point density ( Br v ), end point density ( E v ), and the fractal dimension ( D f , measured by a box-counting algorithm) [5, 17-19, 22, 23, 29, 30]. The space-filling properties of complex objects such as vertebrate vascular branching, arboreal trees, coastlines, and angiosperm leaves are measured by fractal mathematics, a non-Euclidean geometry developed by Mandelbrot and others [31, 32].…”

Section: Vesgen Analysis Softwarementioning

confidence: 99%

“…The syndrome is believed to be associated with the headward fluid shifts that occur in microgravity. We tested the hypothesis that blood vessels in the human retina necessarily remodel in response to these physiological stressors and that the vascular changes measured by VESGEN may provide a sensitive, early-stage predictor of SANS susceptibility [30].…”

Section: Vascular Treesmentioning

confidence: 99%

“…Postflight arterial and venous decreases were quantified by D f and L v in 11/16 retinas [30]. The losses resulted primarily from a decrease in density of small vessels.…”

Section: Vascular Treesmentioning

confidence: 99%

“…Currently, it is not known whether substantial postflight vascular decreases in crew member retinas resulted from vaso-obliteration (vascular dropout or loss), from decreases in the vessel diameter below the limit of image resolution, or from both. This vessel loss is likely associated with the ocular edema that is well documented for SANS and is discussed in more detail elsewhere [30]. Studies of human response to microgravity and space radiation health risks are of increasing importance, given the current global interest in lunar colonization and deep space exploration.…”

Section: Vascular Treesmentioning

confidence: 99%

“…Studies of human response to microgravity and space radiation health risks are of increasing importance, given the current global interest in lunar colonization and deep space exploration. In general, research with VESGEN has revealed that the smaller vessels remodel most actively during progressive vascular-dependent processes such as DR and molecular regulation of angiogenesis and anti-angiogenesis [5, 18, 19, 22, 23, 30, 36, 37, 44, 45].…”

Section: Vascular Treesmentioning

confidence: 99%

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Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis

et al. 2021

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The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA’s globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique “fingerprint” or “biomarker” vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by <i>Saccharomyces boulardii</i>, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

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Section: Vesgen Analysis Softwarementioning

confidence: 99%

Section: Vascular Treesmentioning

confidence: 99%

“…Postflight arterial and venous decreases were quantified by D f and L v in 11/16 retinas [30]. The losses resulted primarily from a decrease in density of small vessels.…”

Section: Vascular Treesmentioning

confidence: 99%

Section: Vascular Treesmentioning

confidence: 99%

Section: Vascular Treesmentioning

confidence: 99%

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Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis

et al. 2021

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Retinal vessel changes in pulmonary arterial hypertension

et al. 2022

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Pulmonary arterial hypertension (PAH) is classically considered an isolated small vessel vasculopathy of the lungs with peripheral pulmonary vascular obliteration. Systemic manifestations of PAH are increasingly acknowledged, but data remain limited. We hypothesized that retinal vascular changes occur in PAH. PAH subjects underwent retinal fluorescein angiography (FA) and routine disease severity measures were collected from the medical record. FA studies were analyzed using VESsel GENerational Analysis (VESGEN), a noninvasive, user‐interactive computer software that assigns branching generation to large and small vessels. FAs from controls (n = 8) and PAH subjects (n = 9) were compared. The tortuosity of retinal arteries was higher in PAH subjects compared to unmatched controls (1.17, 95% confidence interval: [1.14, 1.20] in PAH vs. 1.13, 95% CI: [1.12, 1.14] in controls, p = 0.01). Venous tortuosity was higher and more variable in PAH (1.17, 95% CI: [1.14, 1.20]) compared to controls (1.13, 95% CI: [1.12, 1.15]), p = 0.02. PAH subjects without connective tissue disease had the highest degree of retinal tortuosity relative to controls (arterial, p = 0.01; venous, p = 0.03). Younger PAH subjects had greater retinal arterial tortuosity, which attenuated with age and was not observed in controls. Retinal vascular parameters correlated with some clinical measures of disease in PAH subjects. In conclusion, PAH subjects exhibit higher retinal vascular tortuosity. Retinal vascular changes may track with pulmonary vascular disease progression. Use of FA and VESGEN may facilitate early, noninvasive detection of PAH.

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