Neuronal cell death in the inner retina and the influence of vascular endothelial growth factor inhibition in a diabetic rat model.
To inhibit vascular changes in diabetic retinopathy, inhibiting vascular endothelial growth factor (VEGF) has become a mainstay of the treatment of diabetic retinopathy. However, its effects on neuronal cells remain to be elucidated. We aimed to evaluate the effect of VEGF inhibition on neuronal cells in a streptozotocin-induced diabetic rat retina. VEGF inhibition was performed by intravitreal VEGF-A antibody injection. After anti-VEGF treatment, apoptosis in retinal ganglion cells (RGCs) increased, and novel apoptosis in amacrine and bipolar cells of the inner nuclear layer was observed by TUNEL staining. Phosphorylated Akt expression was significantly higher in RGCs but was decreased in neuronal cells of the inner nuclear layer after anti-VEGF treatment by Western blot analysis and immunohistochemical staining. These results demonstrate that VEGF inhibition significantly increased RGC apoptosis and neuronal cell apoptosis in the inner nuclear layer of a diabetic retina, which seems to consist primarily of amacrine and bipolar cells. The phosphorylated Akt pathway, which plays a neuroprotective role via VEGF, was significantly affected by VEGF inhibition in the inner nuclear layer, suggesting that neurotrophic factor deprivation is the main mechanism for neuronal cell death after inhibiting VEGF. The results of this study show that inhibiting VEGF may have detrimental effects on the apoptosis of neuronal cells in the inner layers of the diabetic retina.
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Hae-Young Lopilly
HY
Park
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Jie Hyun
JH
Kim
Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. Electronic address: ckpark@catholic.ac.kr.
Chan Kee
CK
Park
D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
D057134:Antibodies, Neutralizing; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D051057:Proto-Oncogene Proteins c-akt