International ophthalmology · 2022
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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Zahavi Alon, Friedman Gohas Moran, Sternfeld Amir, Daoud Zreiq Nesrin, Muhsinoglu Orkun, Ofri Ron, BarKana Yaniv, Goldenberg-Cohen Nitza
Аннотация
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.
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.