Affordable Access

deepdyve-link
Publisher Website

Loss of High-Mobility Group Box 1 (HMGB1) Protein in Rods Accelerates Rod Photoreceptor Degeneration After Retinal Detachment

Authors
  • Ross, Bing X.
  • Choi, Joanne
  • Yao, Jingyu
  • Hager, Heather M.
  • Abcouwer, Steven F.
  • Zacks, David N.
Type
Published Article
Journal
Investigative Opthalmology & Visual Science
Publisher
Association for Research in Vision and Ophthalmology (ARVO)
Publication Date
May 27, 2020
Volume
61
Issue
5
Identifiers
DOI: 10.1167/iovs.61.5.50
PMID: 32460314
PMCID: PMC7405795
Source
PubMed Central
Keywords
License
Unknown

Abstract

Purpose Retinal detachment (RD) disrupts the nutritional support and oxygen delivery to photoreceptors (PRs), ultimately causing cell death. High-mobility group box 1 (HMGB1) can serve as an extracellular alarmin when released from stressed cells. PRs release HMGB1 after RD. The purpose of this study was to investigate the relationship between HMGB1 and PR survival after RD. Methods Acute RD was created by injection of hyaluronic acid (1%) into the subretinal space in C57BL/6 mice and mice with a rhodopsin-Cre-mediated conditional knockout (cKO) of HMGB1 in rods (HMGB1ΔRod). Immunofluorescence (IF) in retinal sections was used to localize HMGB1, rhodopsin, and Iba-1 proteins. Optical coherence tomography and electroretinography were used to quantify retinal thickness and function, respectively. The morphology of the retina was assessed by hematoxylin and eosin. Results HMGB1 protein was localized to the nuclei of all retinal neurons, including PRs, with cones staining more intensely than rods. HMGB1 protein was also found in the inner and outer segments of cones but not rods. Creation of RD caused a dramatic increase of HMGB1 protein IF in rods. cKO of HMGB1 in rods did not affect retinal structure or function. However, after RD, loss of rods and reduction in the thickness of the outer nuclear layer were significantly increased in the HMGB1ΔRod retinas as compared to the control. Interestingly, depletion of HMGB1 in rods did not affect the activation and mobilization of microglia/macrophages normally seen after RD. Conclusions Increased HMGB1 expression in stressed rods may represent an intrinsic mechanism regulating their survival after RD.

Report this publication

Statistics

Seen <100 times