Genetic variation in retinal vascular patterning p

Authors: Pranay Prabhakar Hua Zhang De Chen James E Faber

Publish Date: 2014/11/05

Volume: 18, Issue: 1, Pages: 97-114

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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 straindependent 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 Kfold crossvalidation Twentyone metrics varied with strain p  001 Ten metrics eg bifurcation angle lacunarity optimality predicted collateral number and diameter across seven regression models with the best model closely predicting p  00001 number ±12–34 collaterals Kfold R 2 = 083–098 diameter ±12–19 μm R 2 = 073–088 and infarct volume ±51 mm3 R 2 = 085–087 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  00001 collateral number ±33 collaterals Kfold R 2 = 078 and diameter ±16 μm R2  = 086 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

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