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Adenoviral Vector-Mediated Delivery of p21WAF1/CIP1 Prevents Retinal Neovascularization in an Oxygen-Induced Retinopathy Model

ABSTRACT Objective: To evaluate the inhibitory effect(s) of adenovirus (Ad) vector-mediated delivery of p21WAF1/CIP1 (Ad-p21) on retinal neovascularization (RNV) in an animal model of oxygen-induced retinopathy (OIR). Methods: RNV was determined by examination of retinal fiat mounts and sections postnatal (P) day-17 (P17). Non-perfused retinal areas were analyzed using Image-Pro plus 6.0 software. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to measure mRNA and protein expression of p21 and cyclin-dependent kinase (CDK) 2. Results: Compared with phosphate buffer saline (PBS) and Ad-NC group mice, non-perfused retinal areas, neovascularization, and number of endothelial cell nuclei breaking through the internal limiting membrane (ILM) in Ad-p21 group mice were significantly reduced. There were fewer non-perfused retinal areas in Ad-p21 mice than in either PBS or Ad-NC group mice, the differences being significant (F = 101.634; p < 0.05). Levels of p21 mRNA and protein in the Ad-p21 group had increased significantly compared with the other three groups (F = 839.664, 509.817; p < 0.05). Levels of CDK2 mRNA and protein in the Ad-p21 group decreased significantly (F = 301.858, 592.882; p < 0.05). Conclusions: Ad-p21 inhibits RNV in OIR. A potential underlying mechanism for this may be that overexpression of p21 arrests the cell cycle at the G1- to S-phase transition via inhibition of CDK2 activity.