Biology subjects

Gnanaguru, G.

Publications and source records attributed to Gnanaguru, G..

3 recordsLinked to original sources

bioRxiv2026

NDUFA4L2 rescues hyperoxia-induced migration defects in retinal endothelial cells by reversing isocitrate dehydrogenase flux blockade

Retinopathy of prematurity (ROP) is caused by hyperoxic exposure of prematurely born infants. The mouse model of oxygen-induced retinopathy (OIR) recapitulates pathological features of both phase I and phase II ROP. We here looked at the retinal proteins that change in response to hyperoxia in phase I of the mouse model of OIR. Using tandem mass tag labeled proteomics, we found several differentially expressed proteins (DEPs) in phase I of OIR. Of all the DEPs, we investigated the role of previously unknown protein NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2). NDUFA4L2 protein and its paralog NDUFA4 are both mitochondrial complex I proteins; however, here we demonstrate that NDUFA4L2 changes in both phases of OIR, with no changes in its paralog NDUFA4, implying its unique function in pathophysiology of the disease. We demonstrate that NDUFA4L2 is an oxygen-sensitive protein and regulates retinal endothelial cell migration by rescuing isocitrate dehydrogenase flux impaired by hyperoxia in phase I of OIR.

biochemistry↗

bioRxiv2024

Microglial depletion decreases Müller cell maturation and inner retinal vascular density

The neuroretinal vascular system is comprised of three interconnected layers. The initial superficial vascular plexus formation is guided by astrocytes around birth in mice. The formation of the deep and intermediate vascular plexuses occurs in the second postnatal week and is driven by Muller-cell-derived angiogenic signaling. Previously, we reported that microglia play an important role in regulating astrocyte density during superficial vascular plexus formation. Here, we investigated the role for microglia in regulating Muller-cell-dependent inner retinal vascular development. Results from this study show that microglia closely interact with Muller cells and the growing inner retinal vasculature. Depletion of microglia resulted in reduced inner retinal vascular layers densities and decreased Vegfa isoforms transcript levels. RNA-seq analysis further revealed that microglial depletion significantly reduced specific Muller cell maturation markers including glutamine synthetase, responsible for glutamine biosynthesis, which is needed for angiogenesis. Thus, our study reveals an important role for microglia in Muller cell maturation and inner retinal angiogenesis.

cell biology↗

bioRxiv2022

Complement facilitates developmental microglial pruning of astrocyte and vascular networks

Microglia, the resident immune cell of the central nervous system (CNS), play a pivotal role in facilitating neurovascular development through mechanisms that are not fully understood. This current work resolves a previously unknown role for microglia in facilitating the developmental pruning of the astrocytic template resulting in a spatially organized retinal superficial vascular bed. Mechanistically, our study identified that local microglial expression of complement (C)3 and C3aR is necessary for the regulation of astrocyte patterning and vascular growth during retinal development. Ablation of retinal microglia and deficiency of C3 or C3aR reduced developmental pruning and clearance of astrocytic bodies leading to increased astrocyte density, altered vascular patterning, and elevated gene expression levels of extracellular matrix proteins involved in vascular growth during retinal development. These data demonstrate that C3/C3aR signaling is an important checkpoint required for the finetuning of vascular density during neuroretinal development.

developmental biology↗