July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Specificity protein 1 (Sp-1) Regulates Transcription of the Leucine rich repeat and Immunoglobin-like domain-containing protein 1 (LINGO-1) in Optic nerve crushed rat retina
Author Affiliations & Notes
  • Wu Yali
    Zhongshan Ophthalmic Cengter,Sun Yat-sen University, Guangzhou, Guangdong, China
  • Zongyi Zhan
    Zhongshan Ophthalmic Cengter,Sun Yat-sen University, Guangzhou, Guangdong, China
  • Yadan Quan
    Zhongshan Ophthalmic Cengter,Sun Yat-sen University, Guangzhou, Guangdong, China
  • Kaili Wu
    Zhongshan Ophthalmic Cengter,Sun Yat-sen University, Guangzhou, Guangdong, China
  • Minbin Yu
    Zhongshan Ophthalmic Cengter,Sun Yat-sen University, Guangzhou, Guangdong, China
  • Footnotes
    Commercial Relationships   Wu Yali, None; Zongyi Zhan, None; Yadan Quan, None; Kaili Wu, None; Minbin Yu, None
  • Footnotes
    Support  National Natural Science Foundation of China 81870655
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1623. doi:
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      Wu Yali, Zongyi Zhan, Yadan Quan, Kaili Wu, Minbin Yu; Specificity protein 1 (Sp-1) Regulates Transcription of the Leucine rich repeat and Immunoglobin-like domain-containing protein 1 (LINGO-1) in Optic nerve crushed rat retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1623.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : LINGO-1 is essential for neuronal differentiation, growth, the regulation of axon guidance and promotes neuronal apoptosis after injury. Previous studies have indicated the involvement of LINGO-1 in the neuropathological process of spinal cord injury and optic nerve injury. Here, we used the rat optic nerve crush models to determine the mechanisms underlying the transcriptional regulation of LINGO-1.

Methods : Optic nerve crush model was established in rats. Sp1 and LINGO-1 expression was investigated using immunohistochemistry and western bolting. Retinal ganglion cells (RGCs) density, axon regeneration was investigated by whole-mount retina post injury. Primary RGCs from rat retina were isolated by immunopanning using anti-Thy-1 antibody and cultured. RGCs apoptosis were determined by Tunnel assay at different points after serum deprived. In vitro assay was used to examine LINGO-1 level after overexpression of Sp1.The Luciferase assay was used to examine the binding of Sp1 to the promoter regions of LINGO-1.

Results : Both Sp1 and LINGO-1 were expressed in RGCs and upregulated concurrently after ONC. Primary RGCs cells were successfully isolated and identified. RGCs apoptosis was induced when treated with recombinant LINGO-1 or Nogo-66 under serum deprivation. Manipulated with sp1 RNAi resulted in protective effort on RGCs survival. In vitro studies demonstrated that Sp1 overexpression promoted LINGO-1 transcription and this effect was inhibited by mithramycin A. Luciferase assay revealed that Sp1 was required for Lingo-1 promoter activity in rat retina.

Conclusions : Our findings suggest that Sp1 regulates the expression of LINGO-1 in rat retina after optic nerve crush and play an important role in RGCs pathological processes.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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