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Genetic variation in retinal vascular patterning predicts variation in pial collateral extent and stroke severity

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Genetic variation in retinal vascular patterning predicts variation in pial collateral extent and stroke severity

Content Provider	Springer Nature Link
Author	Prabhakar, Pranay Zhang, Hua Chen, De Faber, James E.
Copyright Year	2014
Abstract	The presence of a native collateral circulation in tissues lessens injury in occlusive vascular diseases. However, differences in genetic background cause wide variation in collateral number and diameter in mice, resulting in large variation in protection. Indirect estimates of collateral perfusion suggest that wide variation also exists in humans. Unfortunately, methods used to obtain these estimates are invasive and not widely available. We sought to determine whether differences in genetic background in mice result in variation in branch patterning of the retinal arterial circulation, and whether these differences predict strain-dependent differences in pial collateral extent and severity of ischemic stroke. Retinal patterning metrics, collateral extent, and infarct volume were obtained for 10 strains known to differ widely in collateral extent. Multivariate regression was conducted, and model performance was assessed using K-fold cross-validation. Twenty-one metrics varied with strain (p < 0.01). Ten metrics (e.g., bifurcation angle, lacunarity, optimality) predicted collateral number and diameter across seven regression models, with the best model closely predicting (p < 0.0001) number (±1.2–3.4 collaterals, K-fold R 2 = 0.83–0.98), diameter (±1.2–1.9 μm, R 2 = 0.73–0.88), and infarct volume (±5.1 mm3, R 2 = 0.85–0.87). An analogous set of the most predictive metrics, obtained for the middle cerebral artery (MCA) tree in a subset of the above strains, also predicted (p < 0.0001) collateral number (±3.3 collaterals, K-fold R 2 = 0.78) and diameter (±1.6 μm, R2 = 0.86). Thus, differences in arterial branch patterning in the retina and the MCA trees are specified by genetic background and predict variation in collateral extent and stroke severity. If also true in human, and since genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar “retinal predictor index” could serve as a non- or minimally invasive biomarker for collateral extent in brain and other tissues. This could aid prediction of severity of tissue injury in the event of an occlusive event or development of obstructive disease and in patient stratification for treatment options and clinical studies.
Starting Page	97
Ending Page	114
Page Count	18
File Format	PDF
ISSN	09696970
Journal	Angiogenesis
Volume Number	18
Issue Number	1
e-ISSN	15737209
Language	English
Publisher	Springer Netherlands
Publisher Date	2014-11-05
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Retinal circulation Collateral circulation Cerebral circulation Ischemic stroke Mouse genetics Vascular patterning Cancer Research Biomedicine general Cell Biology Cardiology Ophthalmology Oncology
Content Type	Text
Resource Type	Article
Subject	Physiology Clinical Biochemistry Cancer Research

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