Abstract
BackgroundRapamycin (RAPA) is a potent angiogenic inhibitor and the aim of this study is to identify the inhibitory effect of RAPA on retinal neovascularization (RNV) in experimental oxygen-induced retinopathy (OIR).MethodsForty-two 7-day-old C57BL/6 J mice were randomly divided into normoxia control group (14 mice), OIR group (14 mice), and rapamycin (RAPA) group. OIR model was induced in OIR and RAPA group. Vehicle and RAPA (2 mg/kg/d) was injected intraperitoneally daily from postnatal day 12 (P12) in OIR and RAPA groups, respectively. RNV was evaluated using fluorescence angiography and histopathology on P17. Non-perfused areas of retina were analyzed by Image-Pro plus 6.0 software. Retinal expression of cyclin D1 was detected both at mRNA and protein levels.ResultsRAPA treatment significantly decreased RNV, non-perfused areas and number of endothelial cell nuclei breaking through the internal limiting membrane (ILM) in OIR mice. Moreover, RAPA decreased activation of cyclin D1 in retina caused by OIR.ConclusionRAPA can inhibit RNV by downregulating the expression of cyclin D1, which indicates its therapeutic potential in treating RNV-related diseases.
Highlights
Rapamycin (RAPA) is a potent angiogenic inhibitor and the aim of this study is to identify the inhibitory effect of RAPA on retinal neovascularization (RNV) in experimental oxygen-induced retinopathy (OIR)
Compared to OIR group, the ratio of non-perfused area to total retinal area was lower in RAPA group (0.018 ± 0.007 VS 0.059 ± 0.08; t = 8.780, p < 0.001), which demonstrates a strong inhibitory effect of RAPA on RNV in OIR model. (Fig. 1)
hematoxylin and eosin (H&E) stained retina sections are shown in Fig. 2, and the degree of RNV was quantified in serial 5-μm cross sections by counting the number of vascular cell nuclei on vitreous side of internal limiting membrane (ILM)
Summary
Rapamycin (RAPA) is a potent angiogenic inhibitor and the aim of this study is to identify the inhibitory effect of RAPA on retinal neovascularization (RNV) in experimental oxygen-induced retinopathy (OIR). Angiogenesis, the process responsible for RNV, brings about cellular and morphological changes, including endothelial cells (ECs) activation [2]. Mammalian target of rapamycin (mTOR) protein plays key roles in the activation of quiescent ECs [3], and mTOR inhibitors induce G1 cell cycle arrest [4], resulting in inhibition of ECs proliferation, migration and tube. Our intent was to demonstrate that RAPA prevents RNV in an oxygen-induced retinopathy (OIR) model
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