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Maryam Hejazi, Jamie Zagozewski, Pranidhi Baddam, Daniel Graf, Yves Sauve, David Eisenstat; Persistent fetal vasculature in Nrp2 knockout eye. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3111. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The developing retina is supplied by the choroid and transient hyoid vasculature system.The hyaloid vasculature consists of transient blood vessels which regress in the mature retina.Failure of hyaloid vessel regression results in the development of a condition referred to as Persistent Fetal Vasculature (PFV).Neuropilins (Nrp1 and Nrp2) are described as non-catalytic co-receptors for VEGF and class-3 semaphorins.They are critical for vascular and neuronal development. We have found phenotypic similarities between the Nrp2 knock out (KO) mouse and human PFV.Given the importance of neuropilins in angiogenesis and migration, we hypothesized that Nrp2 may also be necessary for the development of the embryonic retinal vasculature.
We used the Nrp2 KO mouse, of which both heterozygous and mutants are viable and fertile.To understand the temporal and spatial expression of Nrp2, we performed immunostaining on E13, and E18 retina and X-gal staining (a β-galactosidase cassette is present in the Nrp2-gene-trap mouse) on adults.To examine the overall histology of the eyes in postnatal Nrp2 mutants, we performed H&E staining.We utilized Optical Coherence Tomography (OCT) and Electroretinography (ERG) to image Nrp2 KO adult mouse eyes to investigate retinal lamination and physiology in vivo.
NRP2 expression was found in the transient hyaloid vasculature and the choroidal vasculature at E13.At E18, NRP2 expression was observed in the ganglion cell layer (GCL) and in the remnants of the hyaloid vasculature.In the adult retina, X-gal expression was observed in the GCL as well as the inner nuclear layer.In the E13 Nrp2 null retina, the neuroblastic layer was expanded and an accumulation of hyaloidal cells was observed in the vitreal space.By E18, a large retrolental mass is present in the vitreous and the GCL is expanded. The Nrp2 KO eye had substantial retinal folding compared to the WT control.OCT revealed an expanded IPL, Retinal Pigmented Epithelium detachment and dysplasia near the optic cup in Nrp2 null retina compared to the WT controls.
The expression pattern of Nrp2 suggests that Nrp2 is required in multiple aspects of ocular development including the development of inner retinal cells and the hyaloid vasculature.Our results indicate that the loss of Nrp2 expression results in significant ocular abnormalities including those is typically observed secondary to PFV such as microphthalmia and retinal folding.
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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