CircXPO5 Plays a Neuroprotective Function in the Lateral Geniculate Nucleus of Glaucoma by Regulating GRIN2A

Abstract

Purpose: Previous studies have found the neurodegeneration and atrophy of glaucomatous lateral geniculate nucleus (LGN), but the mechanism is still unknown. Circular RNA (circRNA) plays some important roles in physiological and pathological progression of the disease. In this study, we focused on the differentially expressed circRNAs and the mechanism for circXPO5 in LGN degeneration in a macaque glaucoma model. Methods: Using RNA-seq, we analyzed the differentially expressed circRNAs in a macaque glaucoma model. An RT-QPCR was used to check the expression of selected differentially expressed circRNAs, candidate miRNAs and mRNAs. A competing endogenous RNA (ceRNA) network analysis was performed to examine the mechanism of circXPO5 action. Results: circXPO5 significantly decreased in the glaucoma model and a ceRNA network analysis revealed that circXPO5 can bind to miR-330-5p, which also binds to GRIN2A (ionotropic receptor NMDA type subunit 2A). QPCR detection showed a decrease in GRIN2A and an increase in miR-330-5p. Conclusions: Our earlier studies revealed that the GRIN2A gene regulates the calcium signal pathway. Decreasing of GRIN2A related with neuron apoptosis and neurodegeneration. These findings indicate that the reduction in circXPO5 may have a protective effect on neuronal apoptosis in the visual central system of glaucoma.

Regulation of rat HspB5/alphaB-Crystallin by microRNAs miR-101a-3p, miR-140-5p, miR-330-5p, and miR-376b-3p

“…HspB5 is upregulated by several transcription factors, the most important being heat shock factor 1 (HSF1)(De Thonel et al 2012 ). Among validated target genes for miR-330-5p that might be relevant in the CNS are the NMDA receptor GRIN2A (Yan et al 2022 ) and the glial glutamate transporter GLT-1 (Li et al 2022 ). GRIN2A is known to activate the PI3K/Akt pathway under stress conditions (Wu and Tymianski 2018 ).…”

The Application of MicroRNAs in Glaucoma Research: A Bibliometric and Visualized Analysis

“…Interestingly, lncRNAs may emerge as competing endogenous RNAs (ceRNAs) and can potentially correspond to specific messenger RNAs (mRNAs) through sponging to their target miRNAs [144][145][146]. Moreover, miRNAs can bind to their specific mRNAs and repress their expressions in the ceRNA network.…”

“…Similar to lncRNAs, circRNAs can also function as ceRNAs for miRNAs, whereby miRNAs play certain modulatory effects on mRNAs. For example, Zhichao Yan et al [146] suggested that circXPO5 and GRIN2A can act as ceRNAs and compete with miR-330-5p to reduce circXPO5, which will have beneficial effects for glaucoma patients. CeRNAs are related to the molecular mechanisms in ocular disease, such as age-related macular degeneration [151]; thus, a ceRNAs network analysis can efficiently identify molecules related to their regulation.…”