Inhibition of the leucine‑rich repeat protein lingo‑1 enhances RGC survival in optic nerve injury

Quan,Yadan; Wu,Yali; Zhan,Zongyi; Yang,Yangfan; Chen,Xiaotao; Wu,Kaili; Yu,Minbin

doi:10.3892/etm.2019.8250

Inhibition of the leucine‑rich repeat protein lingo‑1 enhances RGC survival in optic nerve injury

Authors:
- Yadan Quan
- Yali Wu
- Zongyi Zhan
- Yangfan Yang
- Xiaotao Chen
- Kaili Wu
- Minbin Yu
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Affiliations: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑Sen University, Guangzhou, Guangdong 510060, P.R. China
Published online on: November 27, 2019 https://doi.org/10.3892/etm.2019.8250
Pages: 619-629
Copyright: © Quan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Leucine‑rich repeat and immunoglobulin‑like domain‑containing nogo receptor‑interacting protein 1 (lingo‑1) is selectively expressed on neurons and oligodendrocytes in the central nervous system and acts as a negative regulator in neural repair, implying a potential role in optic neuropathy. The aim of the present study was to determine whether adeno‑associated virus serotype 2 (AAV2) vector‑mediated transfer of lingo‑1 short hairpin RNA could reduce nerve crush‑induced axonal degeneration and enhance axonal regeneration following optic nerve (ON) injury in vivo. The expression of lingo‑1 was knocked down in vivo using a green fluorescent protein (GFP)‑tagged AAV2 encoding lingo‑1 shRNA via intravitreal injection in adult Sprague‑Dawley rats. Silencing effects of AAV2‑lingo‑1‑shRNA were confirmed by detecting GFP labelling of RGCs, and by quantifying lingo‑1 expression levels with reverse transcription‑quantitative polymerase chain reaction and western blotting. Rats received an intravitreal injection of AAV2‑lingo‑1‑shRNA or negative control shRNA. The ON crush (ONC) injury was performed 2 weeks after the intravitreal injection. RGC density, lesion volume of the injured ON and the visual electrophysiology [flash visual evoked potential (F‑VEP)] at different time points post‑injury were determined. Transduction with lingo‑1‑shRNA decreased lingo‑1 expression levels and promoted RGC survival following ONC. Lingo‑1‑shRNA promoted ON tissue repair and functional recovery. The mechanism underlying the effect of AAV2‑lingo‑1‑shRNA on RGCs may be the phosphorylation of protein kinase B (Akt) at Ser473 and activation of the Akt signaling pathway acting downstream of lingo‑1. The results of the current study indicate that the inhibition of lingo‑1 may enhance RGC survival and facilitate functional recovery following ON injury, representing a promising potential strategy for the repair of optic neuropathy.

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