Structural and functional changes in retinal vasculature induced by retinal ischemia-reperfusion in rats.
Recent studies have shown retinal blood vessel damage in experimental models of retinal degeneration. The present study aimed to provide a detailed description of the structural and functional changes in retinal vasculature induced by retinal ischemia-reperfusion (I/R) in rats. Retinal ischemia was induced for 60 min by raising the intraocular pressure to 130 mmHg. Morphological changes in vascular components (endothelial cells, pericytes, and basement membranes), the patency and perfusion of blood vessels, and expression of vascular endothelial growth factor (VEGF) were assessed in the retinas at 2, 7, and 14 days after I/R. Significant reductions in vascular densities were observed at 7 and 14 days after I/R. Pericyte loss occurred after the appearance of endothelial cell degeneration, whereas the vascular basement membranes remained unchanged. Some vessels showed no perfusion in damaged retina. A decrease in the immunoreactivity of VEGF in the region extending from the ganglion cell layer to the outer plexiform layer was evident 2 days after I/R. In retinal I/R model, retinal ganglion cells are rapidly (<2 day) damaged following reperfusion, therefore, the current results suggest that neuronal cell damage precedes capillary degeneration, and neuronal cells may play an important role in maintaining vascular structure and function through the production and release of endothelial cell survival factors, including VEGF. Neuronal cell damage could be an additional cause of progression of ischemic retinal damage by reducing blood supply to the retinal neurons due to the destruction of the blood vessel network.
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. Electronic address: nakaharat@pharm.kitasato-u.ac.jp.
Tsutomu
T
Nakahara
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Maya
M
Hoshino
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Shin-Ichiro
S
Hoshino
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Asami
A
Mori
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Kenji
K
Sakamoto
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Kunio
K
Ishii
D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D002196:Capillaries / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020286:Pericytes / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000473:pathology; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D055351:Retinal Neurons / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A
Endothelial cells; Pericytes; Retinal neuron damage; Vascular damage; Vascular endothelial growth factor