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Optic neuropathy and increased retinal glial fibrillary acidic protein due to microbead-induced ocular hypertension in the rabbit

Citation

Zhao, J and Zhu, TH and Chen, WC and Peng, SM and Huang, XS and Cho, KS and Chen, DF and Liu, GS, Optic neuropathy and increased retinal glial fibrillary acidic protein due to microbead-induced ocular hypertension in the rabbit, International Journal of Ophthalmology, 9, (12) pp. 1732-1739. ISSN 2222-3959 (2016) [Refereed Article]


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Copyright 2016 IJO Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode

DOI: doi:10.18240/ijo.2016.12.05

Abstract

Aim: To characterize whether a glaucoma model with chronic elevation of the intraocular pressure (IOP) was able to be induced by anterior chamber injection of microbeads in rabbits.

Methods: In order to screen the optimal dose of microbead injection, IOP was measured every 3d for 4wk using handheld applanation tonometer after a single intracameral injection of 10 L, 25 L, 50 L or 100 L microbeads (5106 beads/mL; n=6/group) in New Zealand White rabbits. To prolong IOP elevation, two intracameral injections of 50 L microbeads or phosphate buffer saline (PBS) were made respectively at days 0 and 21 (n=24/group). The fellow eye was not treated. At 5wk after the second injection of microbeads or PBS, bright-field microscopy and transmission electron microscopy (TEM) were used to assess the changes in the retina. The expression of glial fibrillary acidic protein (GFAP) in the retina was evaluated by immunofluorescence, quantitative real-time polymerase chain reaction and Western blot at 5wk after the second injection of microbeads.

Results: Following a single intracameral injection of 10 L, 25 L, 50 L or 100 L microbead, IOP levels showed a gradual increase and a later decrease over a 4wk period after a single injection of microbead into the anterior chamber of rabbits. A peak IOP was observed at day 15 after injection. No significant difference in peak value of IOP was found between 10 L and 25 L groups (17.131.25 mm Hg vs 17.630.74 mm Hg; P=0.346). The peak value of IOP from 50 L group (23.251.16 mm Hg) was significantly higher than 10 L and 25 L groups (all P<0.05). Administration of 100 L microbead solution (23.000.93 mm Hg) did not lead to a significant increase in IOP compared to the 50 L group (P=0.64). A prolonged elevated IOP duration up to 8wk was achieved by administering two injections of 50 L microbeads (20.481.21 mm Hg vs 13.600.90 mm Hg in PBS-injected group; P<0.05). The bright-field and TEM were used to assess the changes of retinal ganglion cells (RGCs). Compared with PBS-injected group, the extended IOP elevation was associated with the degeneration of optic nerve, the reduction of RGC axons (47.16%, P<0.05) and the increased GFAP expression in the retina (4.741.10 vs 1.000.46, P<0.05).

Conclusion: Two injections of microbeads into the ocular anterior chamber of rabbits lead to a prolonged IOP elevation which results in structural abnormality as well as loss in RGCs and their axons without observable ocular structural damage or inflammatory response. We have therefore established a novel and practical model of experimental glaucoma in rabbits.

Item Details

Item Type:Refereed Article
Keywords:glial fibrillary acidic protein, microbead, ocular hypertension, optic neuropathy, rabbit
Research Division:Biomedical and Clinical Sciences
Research Group:Medical biotechnology
Research Field:Gene and molecular therapy
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Liu, GS (Associate Professor Guei-Sheung Liu)
ID Code:120663
Year Published:2016
Web of Science® Times Cited:4
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-08-30
Last Modified:2018-03-16
Downloads:68 View Download Statistics

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