Ndr2 kinase: a novel player in the regulation of microglia in diabetic retinopathy

Overview

Project Summary

Diabetes and its related complications, including conditions like diabetic retinopathy (DR), pose a swiftly growing challenge to health, society, and the economy. DR is a complex disease with a chronic inflammatory component. Many genetic and environmental factors have been considered to contribute to its development. However, the molecular mechanisms underlying the inflammation associated with the pathophysiology of the DR are not all characterized. Recent studies have demonstrated the importance of the Hippo pathway in inflammation. While most of the studies focus on the Lats1 and Lats2 kinases and ignore the Ndr1 (Stk38) and Ndr2 (Stk38L) kinases, it is known that Ndr kinases play a role in innate immunity by regulating the Interleukin 17 (IL-17) and the nuclear factor-κB (NF-κB)-dependent inflammation pathways in macrophages, immune cells that share similarities with microglial cells. However, the role of Ndr2 kinases on microglial inflammatory response and in the pathophysiology of DR awaits to be uncovered.

Main Goals

This project aims at demonstrating how Ndr signaling could be a potential therapeutic target pathway for preventing microglial-induced retinal neural dysfunction and degeneration triggered by diabetes. We will evaluate the role of Ndr2 kinase 1) on inflammation and NF-kB signaling in microglial cells; and 2) on the crosstalk between microglial and endothelial cells. This study will open new avenues for future studies about the Hippo kinase Ndr2 in retinal degenerative diseases.

Project Details