PR002912 (Project)

Dcc Asset:

MW submission packet 20260310.zip

Processed File (Entity type)

Dcc:

Metabolomics

DCC (Entity type)

Child Project:

PPR00001

Project (Entity type)

Persistent Id:http://dx.doi.org/10.21228/M8886D

Description:Retinal ganglion cells (RGCs) have exceptionally high energetic demands, rendering them particularly susceptible to metabolic dysfunction and mitochondrial instability—key drivers of glaucomatous neurodegeneration. However, therapeutic strategies to restore mitochondrial homeostasis in human RGCs remain unexplored. We modeled mitochondrial dysfunction in human retinal ganglion–like cells (RGLCs) and compared the neuroprotective efficacy of small extracellular vesicles (sEVs) derived from undifferentiated BRN3B-H9 cells or lineage-tailored RGLCs. RGLC-derived sEVs enhanced neuronal survival and preserved axonal integrity following mitochondrial injury, effects that were recapitulated in mouse mixed retinal cultures. Untargeted metabolomics revealed extensive remodelling of oxidative phosphorylation, amino acid and lipid metabolism, and redox pathways, with functional validation demonstrating restoration of mitochondrial–glycolytic balance. Importantly, these bioenergetic benefits translated into improved RGC survival across retinal topography in a mouse model of ocular hypertension. Together, our findings identify lineage-tailored sEVs as a promising candidate for restoring mitochondrial homeostasis and enhancing neuroprotection in glaucomatous neurodegeneration.

Results found

Linked to

	Label	Description
	SA546662 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project
	SA546651 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project
	SA546659 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project
	SA546655 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project
	SA546666 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project
	SA546664 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project
	SA546663 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project
	SA546658 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project
	SA546657 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project
	SA546660 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002912 project