The mouse retina in 3D: quantification of vascular growth and remodeling

Abstract

The mouse retina has become a prominent model for studying angiogenesis. The easy access and well-known developmental progression have significantly propelled our ability to examine and manipulate blood vessels in vivo. Nonetheless, most studies have restricted their evaluations to the superficial plexus (an upper vascular layer in contact with the vitreous). Here we present experimental data and quantification for the developmental progression of the full retina including the intermediate and deeper plexus that sprouts from the superficial layer. We analyze the origin and advancement of vertical sprouting and present the progression of vascular perfusion within the tissue. Furthermore, we introduce the use of Minkowsky functionals to quantify remodeling in the superficial and deeper plexus. The work expands information on the retina towards a 3D structure. This is of particular interest, as recent data have demonstrated differential effects of gene deletion on the upper and deeper plexus, highlighting the concept of distinct operational pathways during sprouting angiogenesis.

Chloride intracellular channel 4 is required for maturation of the cerebral collateral circulation

“…Deletion also had no effect on angiogenesis in the aorta ring assay. Consistent with these findings, a previous study (43) found that formation of the outer retinal plexus appeared normal in Clic4 Ϫ/Ϫ mice during (P4) and near the end (P7) of the radial outgrowth phase, a phase dominated by angiogenic sprouting and capillary plexus formation (9,25), although the leading edge of the plexus tended to reach the outer retinal margin slightly later. However, on P21 the mature capillary bed had a lower number of branch points and overall vessel density (43).…”

“…However, on P21 the mature capillary bed had a lower number of branch points and overall vessel density (43). Maturation of the early retinal plexus into artery and vein trees and intervening capillaries involves selective pruning and repatterning processes that occur concurrently with radial outgrowth and are complete by P15 (9,25). Our observation that CLIC4 is required for pruning and maturation of the nascent collateral circulation has analogy to the deficiencies in retinal vascular remodeling (43).…”

Morphogenesis of 3D vascular networks is regulated by tensile forces

“…Distinct differences in vascular network morphology exist between tissue types, where, for example, vessels are aligned in parallel to muscle fibers but take on a radial organization in the retinal lumen (20). We hypothesized that tensile forces applied by and on the cells during network assembly play a central role in determining vascular network morphology and properties.…”

SEM++: A particle model of cellular growth, signaling and migration

“…The introduction of spatially varying SCE potentials, elliptically shaped potential functions or fixed bonds in-between SCEs could address these limitations. Ongoing work focuses on the coupling of particle model with experimental data [20,40,41] and the quantification of uncertainties in the force field following related work of our group on Molecular Dynamics [6].…”

“…It is therefore important for future works to carefully calibrate such migration models with experimental data. Data from wound healing assays [20,40] or the growth of blood vessels in the mouse retina [41] could be used to fit parameters for the models and to quantify their uncertainties [6].…”