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Tailoi Chan-Ling, Louise C Baxter, Samuel J Adamson; “Delayed Retinal Vascularization”: Initiating event in the pathogenesis of retinopathy of prematurity (ROP).. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2773.
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© ARVO (1962-2015); The Authors (2016-present)
In normal development, a balance between neuronal maturation, glial interaction, and retinal vascular formation mediated by ‘physiological hypoxia’ matches the metabolic needs of the tissue with the density of retinal vessels. The key pathogenic event in ROP is hyperoxia induced downregulation of VEGF (Phase 1 ROP) resulting in a delayed rate of retinal vascularization relative to neuronal maturation (which continues normally under hyperoxia). Because of this “delayed vascularization”. the metabolic demand of retinal neurons is mismatched, and the retina becomes hypoxic, driving VEGF over expression, resulting in uncontrolled vasoproliferation (Phase 2 ROP). We aimed to provide normative data for the rate of retinal vascularization in humans under “physiological hypoxia” in utero, and baseline data for the clinical classification for ‘delayed retinal vascularization’ as a basis for initiation of intervention in ROP.
CD34 and Pax2/GFAP/vimentin immunohistochemistry was applied to human retinal wholemounts at 18, 21, 25, 31 week gestation (WG) and full term (38-40WG), as previously reported (Hughes et.al 2000, Chu et.al 2009) to provide imagery for the entire inner retinal vasculature & astrocyte development in utero. These data were compared with density of mitotic figures in the ventricular layer, ganglion cells, and rod and cone photoreceptor data in the developing fetal retina published previously by other groups.
At 18, 21, 25, 31 38-40WG the superficial retinal plexus covered 53, 77, 73, 88 and 99.97% of the total retinal area respectively. We provide the first time-series of the entire retinal vascular bed showing details of lobular topography; branching pattern; capillary density and normal retinal vascular formation in human in utero development, and relationships between the extent of the retinal vasculature & the location & density of neuronal cells.
This normative data gives clinicians managing premature infants the ability to determine if the extent of retinal vascularization is delayed relative to normal in utero development in terms of vascular density, extent & morphology along with distributions & density of neuronal and glial cells in normal development. This normative data can assist clinicians in recognizing ‘delayed retinal vascularization’, and whether to initiate anti-VEGF or laser therapy
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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