Purchase this article with an account.
Sze Yuan Ho, Beiying Qiu, Yuet Ping Kwan, Gemmy Cheung, Tien Yin Wong, Walter Arthur Wahli, Wanjin Hong, Xiaomeng Wang; Investigating the role of PPARβ/δ in retinal angiogenesis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5414.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
While anti-vascular endothelial growth factor (VEGF) agents have revolutionized the treatment for ocular angiogenic diseases, including proliferative diabetic retinopathy, a substantial proportion of patients are resistant to the therapy. Emerging evidence suggests that targeting cell metabolism may offer an alternative or more effective strategy to control abnormal blood vessel formation. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a member of the nuclear hormone receptor family that have key roles in lipid metabolism. Recent studies have demonstrated a role of PPARβ/δ in regulating ocular angiogenesis. A potent and selective PPARβ/δ agonist, GW501516, was reported to have both lipid lowering and anti-diabetic effects in human trials. However, the effect of GW501516 on retinal angiogenesis remains to be elucidated. Moreover, the underlying molecular and cellular mechanisms of PPARβ/δ in retinal angiogenesis are unclear. In this study, we aim to investigate the impact of PPARβ/δ on retinal angiogenesis.
Trypan blue exclusion and Matrigel tube formation assay were performed using primary human retinal microvascular endothelial cells (HRMECs) to evaluate the role of PPARβ/δ agonist, GW501516, in HRMEC function. Aortic ring sprouting assay was used to investigate the effect of GW501516 on vessel sprouting. PPARβ/δ-/- mouse and wild type control retina were collected to study PPARβ/δ’s role in retinal angiogenesis and vessel remodelling. The expression levels of various angiogenic and vessel remodelling markers were studied by real-time quantitative polymerase chain reaction analysis.
Our study showed that the viability of GW501516-treated HRMECs was increased by 24.0 ± 3.3% (n=3) as compared to vehicle control treated HRMECs. GW501516 also promoted HRMEC tube formation, leading to 31.5 ± 14.6% (n=3) and 20.8 ± 5.6% (n=3) increase in the number of junctions and total tube length respectively. Consistently, GW501516 led to increased aortic ring sprouting by 63.0 ± 17.5%. Interestingly, pericyte coverage was decreased by 8.8 ± 1.0% in the retina of PPARβ/δ-/- mice as compared to those of wild type controls. Additionally, VEGFR2 and PDGFRβ mRNA transcripts were significantly reduced in PPARβ/δ-/- mice retina.
Our results demonstrated that PPARβ/δ agonist GW501516 plays an important role in retinal angiogenesis and that PPARβ/δ could modulate vascular remodelling in the retina.
This is a 2020 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only