Abstract
Purpose :
Glaucoma is a progressive eye disease leading to vision loss and blindness due to death of retinal ganglion cells and damage to the optic nerve. To understand its pathophysiologic mechanisms, various experimental models have been used. Although substantial research on glaucoma has been ongoing, finding pathological mechanisms and further treatment approaches on retinal neuroprotection still remains unclear due to the pathologic complexity. Therefore, in our current study, we attempted to find potential therapeutic molecular targets on retinal neuroprotection via comprehensive combined transcriptome profiling from three different experimental glaucoma models.
Methods :
The NCBI Gene Expression Omnibus (GEO) array-based expression profiling public datasets on the whole retina in DBA/2J, retinal ischemia/reperfusion (I/R) injury, and intraorbital nerve crush (IONC) were prepared (GSE26299, GSE43671, and GSE9918). Furthermore, our dataset on the inner retina obtained by laser-capture micro-dissectioning in retinal I/R injury was made with RT2 profiler PCR array. Combined transcriptome profiling in those datasets was utilized to evaluate changes in gene expressions among experimental models and further identify potential therapeutic molecular targets for glaucoma.
Results :
Intersection analysis on distinct experimental sets identified 325 potential genes (including Lyz2, Edn2, and Tgln2) significantly altered under disease states (p < 0.05). While DBA/2J-I/R mainly shared mTOR, mitophagy, hypoxia-inducible factor-1 (HIF-1), glycolysis, GABAergic synapse, cell cycle, calcium, and autophagy pathways, IONC-I/R relatively shared proteasome, phototransduction, p53, and NF-kB pathways. Combined with our dataset, various genes (including Lgals3 and Ccng2) were identified as important genes under all disease conditions (p < 0.05). PI3K-Akt, cellular senescence, AGE-RAGE, and longevity regulating pathways were further suggested important for inner retinal protection.
Conclusions :
Our current study provides shared potential therapeutic molecular targets for retinal protection against pathologic conditions in various models of glaucoma. These findings can support further preclinical research and offer new possibilities for developing or repositioning therapeutic interventions based on bioinformatics analyses.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.