Müller glia cells regulate Notch signaling and retinal angiogenesis via the generation of 19,20-dihydroxydocosapentaenoic acid

The Pharmacology of the Cytochrome P450 Epoxygenase/Soluble Epoxide Hydrolase Axis in the Vasculature and Cardiovascular Disease

“…Exactly such an approach was used to study the role of PUFA epoxides and diols in postnatal retinal angiogenesis and revealed that the genetic deletion and inhibition of the sEH activates Notch signaling and attenuates sprouting angiogenesis in the murine retina. Mechanistically these effects could be attributed to the lack of the sEH product and DHA diol 19,20-DHDP (Hu et al, 2014). Moreover, 19,20-DHDP was able to rescue the defective angiogenesis in sEH 2/2 mice as well as in animals lacking the Fbxw7 ubiquitin ligase, which demonstrate strong basal activity of the Notch signaling cascade.…”

“…Indeed, the deletion of the sEH in mice is an effective way of manipulating fatty acid epoxide and diol levels in vivo (Sinal et al, 2000). To date, global sEH-deficient animals (Sinal et al, 2000) as well as "floxed" and "inducible" tissue-specific sEH mice have been generated (Hu et al, 2014).…”

“…Whether the various stereo/ regioisomers are incorporated differently into membrane lipids remains to be determined. Perhaps adduction to membrane phospholipids is a more likely mechanism of action of the PUFA-derived diols and can account for the exclusion of presenilin-1 and cholesterol from lipid rafts after exposure to 19,20-DHDP, but not 19,20-EDP (Hu et al, 2014).…”

“…However, the deletion of the sEH in Müller cells clearly affected endothelial cell proliferation as well as Notch signaling and tip cell filopodia formation in mice, indicating that Müller cells make a more important contribution to retinal angiogenesis than generally appreciated. Mechanistically, 19,20-DHDP was found to promote angiogenesis by inducing the redistribution of presenilin 1 from lipid rafts, thus inhibiting the g-secretase and Notch signaling (Hu et al, 2014).…”

Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond

“…Müller cells are specialised radial glia and form the structural and functional link between neurons and blood vessels, handle nutrients and waste products, affect the tightness of the BRB and maintain survival and function of neurons and blood vessels. Several experimental studies show that proper glial function is obligatory for the formation of the deep capillary layers [32][33][34]. Resident microglia have been described as immunological watchdogs of the retina [30,35].…”