Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

Abstract

Background/Aims: The aim of the present study is to investigate the effect of long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC) apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma. Methods: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis. Results: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups. Conclusion: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.

A single‐cell transcriptome atlas of the adult human retina

“…We also noted some heterogeneous MALAT1 expression in other retinal cell types in humans, albeit to a lesser extent compared to rod photoreceptors. Previous studies have demonstrated a role of MALAT1 in regulating the survival of retinal ganglion cells (Li et al, 2017) and in pathogenesis of retinal pigment epithelial cells (Yang et al, 2016). However, the functional role of MALAT1 in photoreceptors remained unclear.…”

Therapeutic Effects of Puerarin Against Anterior Ischemic Optic Neuropathy Through Antiapoptotic and Anti-Inflammatory Actions

“…23,28,31 In addition, some studies have proven that the activation of the PI3K-AKT signaling pathway exerts protective effects on injured RGCs. [46][47][48][49] The PI3K-AKT signaling pathway is activated in response to environmental stimuli, such as cytokines/chemokines and hormones, to regulate cell survival, proliferation, and differentiation. In this study, we observed that treatment with PR maintained Akt1 activation after ON infarct.…”

Generation of human neural retina transcriptome atlas by single cell RNA sequencing

“…We further showed that MALAT1-lo subpopulations represent early degenerating rod photoreceptors, a finding that has not previously been reported in human or any other species. Previous studies have demonstrated a role of MALAT1 in regulating the survival of retinal ganglion cells (Li et al, 2017) and in pathogenesis of retinal pigment epithelium cells . However, the functional role of MALAT1 in photoreceptors remained unclear.…”