Alon Zahavi1,2,3, Moran Friedman Gohas4, Amir Sternfeld5,6, Nesrin Daoud Zreiq4,7, Orkun Muhsinoglu4, Ron Ofri8, Yaniv BarKana9, Nitza Goldenberg-Cohen4,10,11. 1. Department of Ophthalmology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. alonzahavi@gmail.com. 2. Laboratory of Eye Research, Felsenstein Medical Research Center, Petach Tikva, Israel. alonzahavi@gmail.com. 3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. alonzahavi@gmail.com. 4. Krieger Eye Research Laboratory, Rappaport Faculty of Medicine, Technion, Haifa, Israel. 5. Department of Ophthalmology, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel. 6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 7. Department of Ophthalmology, French Hospital, Nazareth, Israel. 8. Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel. 9. The Glaucoma Innovation & Research Lab, The Sam Rothberg Glaucoma Center, Sheba Medical Center, Tel Hashomer, Israel. 10. Department of Ophthalmology, Bnai Zion Medical Center, Haifa, Israel. 11. The Technion, Israel Institute of Technology, Haifa, Israel.
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.
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.
Authors: Mae O Gordon; Julia A Beiser; James D Brandt; Dale K Heuer; Eve J Higginbotham; Chris A Johnson; John L Keltner; J Philip Miller; Richard K Parrish; M Roy Wilson; Michael A Kass Journal: Arch Ophthalmol Date: 2002-06
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Authors: John Kuchtey; Lana M Olson; Tommy Rinkoski; Edward O Mackay; T M Iverson; Kirk N Gelatt; Jonathan L Haines; Rachel W Kuchtey Journal: PLoS Genet Date: 2011-02-17 Impact factor: 5.917