Abstract
Purpose :
Peroxisome Proliferator-Activated Receptor α (PPARα) is a ligand-activated transcription factor in the nuclear hormone receptor superfamily. The function of PPARα signaling in the retinal microvasculature has not been well understood. We have generated mice with PPARα conditional knockout in vascular endothelial cells (ECs) and pericytes to investigate its potential function in retinal vascular development and in vascular pathologies in disease conditions.
Methods :
Endothelium-specific PPARα conditional KO (PPARαECKO) and pericyte-specific PPARα conditional KO (PPARαPCKO) mice were generated by crossing PPARαflox//flox mice with mice expressing Cre under the control of the VE-Cadherin promoter and Pdgfrb promoter, respectively. For the oxygen-induced retinopathy (OIR) model, PPARαECKO, PPARαPCKO and PPARαFLOX pups were fed tamoxifen at 0.2 mg from P4-P6 to induce Cre expression. The pups with nursing mom were placed into 75% oxygen chamber from P7-P12. On P12, the animals were returned to room air and maintained in room air until P17. On P17, the retinas were flat-mounted and stained with isolectin. Avascular areas and neovascularization areas were quantified.
Results :
PPARα KO in the vascular ECs and pericytes resulted in retinal vasculature different from that of PPARαFLOX mice in the OIR model. PPARαECKO and PPARαPCKO mice with OIR both developed enlarged avascular areas in the retina relative to PPARαFLOX OIR mice. However, PPARαPCKO OIR mice showed larger retinal neovascularization areas than those in the PPARαECKO and PPARαFLOX mice. Moreover, the PPARαECKO mice showed smaller neovascularization areas than that of the PPARαFLOX mice in the OIR model.
Conclusions :
We have successfully generated mice with PPARα conditional KO in vascular ECs and pericytes and observed altered retinal microvasculature in disease conditions. These models will allow us to further investigate the function of PPARα in retinal microvasculature.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.