Adenoviral Vector-Mediated Delivery of p21^WAF1/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 p21^WAF1/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.

KEYWORDS:

• Animal experimentation
• gene transfer techniques
• retinal neovascularization/prevention and control
• transfection

Funding

This study was funded by Science and Technology of Tianjin (China) Health Bureau (No. 2012KZ100).

Declaration of interest

The authors declare no conflicts of interest.

Additional information

Funding

This study was funded by Science and Technology of Tianjin (China) Health Bureau (No. 2012KZ100).