SP1‐mediated upregulation of LINGO‐1 promotes degeneration of retinal ganglion cells in optic nerve injury

Abstract

Backgrounds Insults to the axons in the optic nerve head are the primary cause of loss of retinal ganglion cells (RGCs) in traumatic, ischemic nerve injury or degenerative ocular diseases. The central nervous system–specific leucine‐rich repeat protein, LINGO‐1, negatively regulates axon regeneration and neuronal survival after injury. However, the upstream molecular mechanisms that regulate LINGO‐1 signaling and contribute to LINGO‐1–mediated death of RGCs are unclear. Methods The expression of SP1 was profiled in optic nerve crush (ONC)–injured RGCs. LINGO‐1 level was examined after SP1 overexpression by qRT‐PCR. Luciferase assay was used to examine the binding of SP1 to the promoter regions of LINGO‐1. Primary RGCs from rat retina were isolated by immunopanning and RGCs apoptosis were determined by Tunnel. SP1 and LINGO‐1 expression was investigated using immunohistochemistry and Western bolting. Neuroprotection was assessed by RGC counts, RNFL thickness, and VEP tests after inhibition of SP1 shRNA. Results We demonstrate that SP1 was upregulated in ONC‐injured RGCs. SP1 was bound to the LINGO‐1 promoter, which led to increased expression of LINGO‐1. Treatment with recombinant Nogo‐66 or LINGO‐1 promoted apoptosis of RGCs cultured under serum‐deprivation conditions, while silencing of SP1 promoted the survival of RGCs. SP1 and LINGO‐1 colocalized and were upregulated in ONC‐injured retinas. Silencing of SP1 in vivo reduced LINGO‐1 expression and protected the structure of RGCs from ONC‐induced injury, but there was no sign of recovery in VEP. Conclusions Our findings imply that SP1 regulates LINGO‐1 expression in RGCs in the injured retina and provide insight into mechanisms underlying LINGO‐1–mediated RGC death in optic nerve injury.

Longtime Vision Function Prediction in Childhood Cataract Patients Based on Optical Coherence Tomography Images

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Integrated Transcriptome Analysis Reveals the Crucial mRNAs and miRNAs Related to Fecundity in the Hypothalamus of Yunshang Black Goats during the Luteal Phase

“…The novel-miR-1125 targets LINGO-1 , a protein encoded by a leucine-rich repeat (LRR), neurite outgrowth inhibitory protein (Nogo), and immunoglobulin domain (Ig) constitutes the central nervous system transmembrane protein. In a variety of animal models, the targeted inhibition of LINGO-1 can promote the neuronal survival, axon regeneration, and the oligodendrocyte differentiation [ 66 ].…”

Taurine and oxidative stress in retinal health and disease

“…OAG is characterized by degeneration of the trabecular meshwork (TM) which rises the intraocular pressure, which in turn, lead to altered axons of RGCs forming the optical nerve, and then progressive concentric damage of the RGCs. [84][85][86] Degeneration of these cells results in a typical form of the optic disk (cupping) and visual impairment.…”

“…RGC degeneration appears in several retinal disorders leading to visual loss, either as a primary process like in glaucoma or secondary to photoreceptor loss. 86 However, to date, there is no available treatment directly targeting RGCs neuroprotection. As we mentioned above, taurine seems to be essential for photoreceptors' survival since its deprivation is related to retinal death.…”