Histological and molecular characterization of glaucoma model induced by one or two injections of microbeads to the anterior chamber of mice

Alon Zahavi*, Moran Friedman Gohas, Amir Sternfeld, Nesrin Daoud Zreiq, Orkun Muhsinoglu, Ron Ofri, Yaniv BarKana, Nitza Goldenberg-Cohen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Purpose: To characterize glaucoma-induced damage following injections of plastic microbeads into the anterior chamber of mice. Methods: Mice were divided into three groups: a single plastic microbeads injection (n = 21); two consecutive plastic microbead injections to the right eye at 1-week intervals, 4 of which with two consecutive saline injections in the left eye (n = 15); and an additional control group of two consecutive saline injections at 1-week intervals (n = 6). Intraocular pressure (IOP) was measured weekly. Retinal thickness, ganglion cells (RGCs) and axonal loss, inflammatory and gliosis reactions were measured at week four. Molecular analysis using qRT-PCR in the microbeads injection groups focused on expression levels of inflammation and glaucoma-related genes. Results: Mean IOP following single injection at 4 weeks was significantly elevated compared to baseline in injected eyes (14.5 ± 3.3 mmHg vs. 11.1 ± 2.5 mmHg, respectively, p = 0.003) and not in fellow eyes (13.2 ± 2.9 mmHg vs. 12.2 ± 2.9, respectively, NS). Six (35.3%) bead-injected eyes had IOP ≥ 17 mmHg compared with 2 (11.8%) saline-injected control eyes. Retinal thickness in injected and fellow eyes was 193.7 ± 15.5 µm and 223.9 ± 15.5 µm, respectively (p = 0.03). RGC loss in injected and fellow eyes was 16.0 ± 0.5 and 17.6 ± 0.7 cells per 200 µm, respectively (p = 0.005). Retinal gliosis, axonal loss and inflammatory cell infiltration to the bead-injected eyes were noted. Molecular analysis following double injection showed STAT3 expression decreased in the glaucoma-induced optic nerves (0.69 ± 0.3 vs. 1.16 ± 0.3, p = 0.04), but increased in the glaucoma-induced retinae (p = 0.05) versus saline; retinal IL-1β decreased significantly (0.04 ± 0.04 vs. 0.36 ± 0.2, p = 0.02). TNF-α, NFkB and SOD-1 expression did not change. Conclusion: One/two injections of microbeads elevated IOP, with measurable neuronal damage. An inflammatory response was detected in the injured retina and optic nerve. The therapeutic significance of these findings should be explored.

Original languageAmerican English
Pages (from-to)3763-3775
Number of pages13
JournalInternational Ophthalmology
Volume42
Issue number12
Early online date22 Jun 2022
DOIs
StateE-pub ahead of print - 22 Jun 2022

Bibliographical note

Funding Information:
This study was partially supported in part by the Zanvyl and Isabelle Krieger Fund, Baltimore, MD (N.G.-C.). The funding organization had no role in the design or conduct of this research.

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature B.V.

Keywords

  • Glaucoma
  • Intraocular pressure
  • Microbeads
  • Optic nerve

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