Abstract
BackgroundThe retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish.ResultsWe show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO), subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development.ConclusionZebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease.
Highlights
The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals
The inner limiting membrane of the zebrafish retina is covered by a complex system of blood vessels (Fig 1)
The main branches arborise radially from the optic disc eventually anastomosing with neighbouring capillaries before connecting to a circumferential vein (Fig 1D and 1G)
Summary
The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. The adult retina is nourished by two independent circulatory systems, choroidal and retinal vessels. Choroidal vessels overlying the retinal pigmented epithelium (RPE) carry ~80% of retinal blood flow, and nourish the outer retina. The central retinal artery emanating from the optic nerve head carries the remaining ~20% of blood flow and nourishes the inner two thirds of the retina [4]. These retinal vessels develop intraretinal capillaries that ramify at the inner and outer plexiform layers [3,5]. Unique to retinal and brain capillaries, pericytes directly contact the vascular endothelium, are enclosed by the basement membrane and have strong expression of smooth muscle actin conferring contractile function [5,7]
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