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

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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.

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Funding

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.

Author information

Author notes

  1. Alon Zahavi and Moran Friedman Gohas have contributed equally to the work.

Authors and Affiliations

  1. Department of Ophthalmology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel

    Alon Zahavi & Amir Sternfeld

  2. Laboratory of Eye Research, Felsenstein Medical Research Center, Petach Tikva, Israel

    Alon Zahavi

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Alon Zahavi & Amir Sternfeld

  4. Krieger Eye Research Laboratory, Rappaport Faculty of Medicine, Technion, Haifa, Israel

    Moran Friedman Gohas, Nesrin Daoud Zreiq, Orkun Muhsinoglu & Nitza Goldenberg-Cohen

  5. Department of Ophthalmology, French Hospital, Nazareth, Israel

    Nesrin Daoud Zreiq

  6. Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel

    Ron Ofri

  7. The Glaucoma Innovation & Research Lab, The Sam Rothberg Glaucoma Center, Sheba Medical Center, Tel Hashomer, Israel

    Yaniv BarKana

  8. Department of Ophthalmology, Bnai Zion Medical Center, Haifa, Israel

    Nitza Goldenberg-Cohen

  9. The Technion, Israel Institute of Technology, Haifa, Israel

    Nitza Goldenberg-Cohen

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  1. Alon Zahavi
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Correspondence to Alon Zahavi.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

All protocols were conducted in accordance with the Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use of Animals in Ophthalmic and Vision Research and National Institutes of Health guidelines, and were approved and monitored by the Institutional Animal Research Committee.

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Presented in part at Israeli Society of Vision and Eye Research (ISVER) 2017, The Association for Research in Vision and Ophthalmology (ARVO), Baltimore, MD, June 2017.

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Zahavi, A., Friedman Gohas, M., Sternfeld, A. et al. Histological and molecular characterization of glaucoma model induced by one or two injections of microbeads to the anterior chamber of mice. Int Ophthalmol 42, 3763–3775 (2022). https://doi.org/10.1007/s10792-022-02372-9

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  • DOI: https://doi.org/10.1007/s10792-022-02372-9

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