Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2022 Jun 27

PMID 35758906

Authors

Feijia Xie

Zongyuan Li

Ning Yang

Jiayi Yang

Dihao Hua

Jinyuan Luo

Tao He

Yiqiao Xing

Affiliations

Soon will be listed here.

Abstract

Purpose: Heat shock protein B8 (HspB8) can be upregulated rapidly in many pathologic processes, but its role in traumatic optic neuropathy remains unclear. In this study, we investigated the involvement of autophagy in the effects of HspB8 by using the optic nerve crush (ONC) model.

Methods: Male C57BL/6J mice were intravitreally injected with recombinant adeno-associated virus type 2 (AAV2-shHspB8 or AAV2-GFP) and subsequently received ONC by a self-closing tweezers. Western blot and immunohistochemistry staining were used to evaluate the expression of HspB8. We conducted retinal flat-mount immunofluorescence to measure the quantities of retinal ganglion cells (RGCs), and full-field flash electroretinogram (ff-ERG) and optomotor response (OMR) were used to evaluate retinal function. The autophagy level was reflected by western blot, immunohistochemistry staining, and transmission electron microscope (TEM) images. We also applied 3-methyladenine (3MA) and rapamycin (Rapa) to regulate autophagy level in optic nerve injury.

Results: ONC stimulated the expression of HspB8. Declines of RGCs and ff-ERG b-wave amplitudes resulting from ONC can be alleviated by HspB8 downregulation. Increased autophagy activity after ONC was observed; however, this change can be reversed by intravitreal injection of AAV2-shHspB8. Furthermore, application of autophagy inhibitor 3MA had the same neuroprotective effects as AAV2-shHspB8, as illustrated by ff-ERG and quantities of RGCs. Also, protection of AAV2-shHspB8 was compromised by the autophagy activator Rapa.

Conclusions: Inhibition of HspB8 in mice optic nerve injury had neuroprotective effects, which may be derived from its downregulation of autophagy.

Citing Articles

Mettl3-Mediated N6-Methyladenosine Modification Mitigates Ganglion Cell Loss and Retinal Dysfunction in Retinal Ischemia-Reperfusion Injury by Inhibiting FoxO1-Mediated Autophagy.

Zhu F, Feng J, Pan Y, Ouyang L, He T, Xing Y Invest Ophthalmol Vis Sci. 2025; 66(2):58.

PMID: 39982709 PMC: 11855173. DOI: 10.1167/iovs.66.2.58.

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