Sergio Crespo-Garcia1,2,3, Nadine Reichhart4, Jeffrey Wigdahl5, Sergej Skosyrski4, Norbert Kociok4, Olaf Strauß4, Antonia M Joussen4. 1. Experimental Ophthalmology, Department of Ophthalmology, Charité - Universitätsmedizin Berlin, Freie Universität, Humboldt-University, the Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany. sergiocrespogarcia@gmail.com. 2. Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, Université de Montréal, Montréal, Canada. sergiocrespogarcia@gmail.com. 3. Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, Université de Montréal, Montréal, Canada. sergiocrespogarcia@gmail.com. 4. Experimental Ophthalmology, Department of Ophthalmology, Charité - Universitätsmedizin Berlin, Freie Universität, Humboldt-University, the Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany. 5. VisionQuest Biomedical LLC, Albuquerque, NM, USA.
Abstract
PURPOSE: Netrin-4 (NTN4) is a protein that plays an important role in the regulation of angiogenesis in the pathological retina. Some evidences show that it can also have a role in inflammation and vascular stability. We will explore these questions in vivo in the mature mouse retina. METHODS: We created a NTN4 knockout that expresses EGFP in mononuclear phagocytes (CSFR1-positive cells) to track inflammation in vivo in the retina by scanning laser ophthalmoscopy (SLO). Fundus angiography permitted to study blood vessels. Retinal function was assessed with electroretinography (ERG). RESULTS: Lack of NTN4 leads to an increased amount of amoeboid mononuclear phagocytes in the adult retina, and blood vessels displayed increased tortuosity when compared with the wildtype. Inner retina function also seemed affected in NTN4 null. Lack of NTN4 resulted in a higher persistence of hyaloid artery and spontaneous leakage in the adult retina. No differences were found regarding vessel bifurcation, vessel width, or vein/artery ratio. CONCLUSIONS: These in vivo data show for the first time that lack of NTN4 induces changes in the retinal vascular phenotype in a non-pathological scenario. This evidence widens the role of NTN4 as a guidance cue in vascular remodeling.
PURPOSE:Netrin-4 (NTN4) is a protein that plays an important role in the regulation of angiogenesis in the pathological retina. Some evidences show that it can also have a role in inflammation and vascular stability. We will explore these questions in vivo in the mature mouse retina. METHODS: We created a NTN4 knockout that expresses EGFP in mononuclear phagocytes (CSFR1-positive cells) to track inflammation in vivo in the retina by scanning laser ophthalmoscopy (SLO). Fundus angiography permitted to study blood vessels. Retinal function was assessed with electroretinography (ERG). RESULTS: Lack of NTN4 leads to an increased amount of amoeboid mononuclear phagocytes in the adult retina, and blood vessels displayed increased tortuosity when compared with the wildtype. Inner retina function also seemed affected in NTN4 null. Lack of NTN4 resulted in a higher persistence of hyaloid artery and spontaneous leakage in the adult retina. No differences were found regarding vessel bifurcation, vessel width, or vein/artery ratio. CONCLUSIONS: These in vivo data show for the first time that lack of NTN4 induces changes in the retinal vascular phenotype in a non-pathological scenario. This evidence widens the role of NTN4 as a guidance cue in vascular remodeling.
Entities:
Keywords:
Basal membrane; Hyaloid vessel; In vivo imaging; Mononuclear phagocyte; Netrin-4; Vascular remodeling
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