Retinal neuronal cell loss prevents abnormal retinal vascular growth in a rat model of retinopathy of prematurity.

Abstract

A short-term blockade of the vascular endothelial growth factor (VEGF)-mediated pathway in neonatal rats results in formation of severe retinopathy of prematurity (ROP)-like retinal blood vessels. The present study aimed to examine the role of retinal neurons in the formation of abnormal retinal blood vessels. Newborn rats were treated subcutaneously with the VEGF receptor tyrosine kinase inhibitor, KRN633 (10 mg/kg), or its vehicle (0.5% methylcellulose in water) on postnatal day (P) 7 and P8. To induce excitotoxic loss of retinal neurons, N-methyl-D-aspartic acid (NMDA) was injected into the vitreous chamber of the eye on P9. Changes in retinal morphology, blood vessels, and proliferative status of vascular cells were evaluated on P11 and P14. The number of cells in the ganglion cell layer and the thickness of the inner plexiform layer and inner nuclear layer were significantly decreased 2 days (P11) after NMDA treatment. The pattern and degree of NMDA-induced changes in retinal morphology were similar between vehicle-treated (control) and KRN633-treated (ROP) rats. In ROP rats, increases in the density of capillaries, the tortuosity index of arteries, and the proliferating vascular cells were observed on P14. The expansion of the endothelial cell network was prevented, and the capillary density and the number of proliferating cells were reduced in NMDA-treated retinas of both control and ROP rats. Following NMDA-induced neuronal cell loss, no ROP-like blood vessels were observed in the retinas. These results suggest that retinal neurons play an important role in the formation of normal and ROP-like retinal blood vessels.

• Authors: Ayuki Nakano, Daiki Asano, Ryo Kondo, Asami Mori, Shiho Arima, Hiroko Ushikubo, Kenji Sakamoto, Tohru Nagamitsu, Kunio Ishii, Tsutomu Nakahara
• Journal: Experimental eye research (Exp Eye Res) Vol. 168 Pg. 115-127 (03 2018) ISSN: 1096-0007 [Electronic] England
• PMID: 29339088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Phenylurea Compounds
• Protein Kinase Inhibitors
• Quinazolines
• Vascular Endothelial Growth Factor A
• N-Methylaspartate
• N-(2-chloro-4-((6,7-dimethoxy-4-quinazolinyl)oxy)phenyl)-N'-propylurea

Topics

• Animals
• Capillaries (pathology)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• N-Methylaspartate (pharmacology)
• Phenylurea Compounds (pharmacology)
• Protein Kinase Inhibitors (pharmacology)
• Quinazolines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Retina (metabolism, pathology)
• Retinal Ganglion Cells (pathology)
• Retinal Neurons (pathology)
• Retinal Vessels (pathology)
• Retinopathy of Prematurity (pathology)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, metabolism)