Steroid-Induced Ocular Hypertension Model in the Mice

You Ra Kim; Wan SeoK Kang; Eui Yong Kweon; Nam Chun Cho; Dong Wook Lee

doi:10.3341/jkos.2014.55.8.1202

Journal List > J Korean Ophthalmol Soc > v.55(8) > 1009754

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Kim, Kang, Kweon, Cho, and Lee: Steroid-Induced Ocular Hypertension Model in the Mice

Original Article

J Korean Ophthalmol Soc 2014;55(8):1202-1207.

Published online: 31 August 2014

DOI: https://doi.org/10.3341/jkos.2014.55.8.1202

Steroid-Induced Ocular Hypertension Model in the Mice

You Ra Kim, MD, Wan SeoK Kang, MD, Eui Yong Kweon, MD, Nam Chun Cho, MD, Dong Wook Lee, MD

Department of Ophthalmology, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea

Address reprint requests to Dong Wook Lee, MD, Department of Ophthalmology, Chonbuk National University Hospital, #20 Geonji-ro, Deokjin-gu, Jeonju 561-712, Korea, Tel: 82-63-250-1996, Fax: 82-63-250-1960, E-mail: ldw@jbnu.ac.kr

Received 9 November 2013 Revised 11 February 2014 Accepted 12 July 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To determine whether rat eyes develop increases in intraocular pressure (IOP) in response to a topically applied corticosteroid and to investigate the relationship between ocular hypertension and apoptosis of retinal ganglion cells.

Methods

IOP was monitored by rebound tonometry in a group of 10 rats that received topically administered dexamethasone in both eyes (experimental) and in another group of 5 rats that received artificial tears (control) three times daily for 4 weeks after the establishment of baseline IOP values. Only eyes that increased by more than 50% compared with the basal IOP were administered once per day for 5 weeks. After 8 weeks, selective immunofluorescence stain for retinal ganglion cells and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stain were conducted.

Results

Among 20 experimental eyes, 11 eyes (55%) showed a greater than 50% increase in IOP compared with basal IOP. After 8 weeks, the mean IOPs for the experimental and control groups were 11.8 ± 1.4 mm Hg and 18.5 ± 1.0 mm Hg, respectively (p < 0.01). The counts of central retinal ganglion cells (RGCs) were 2718 ± 240 and 2612 ± 443, respectively (p = 0.294). The results of the TUNEL stain also showed no differences.

Conclusions

Rat eyes exhibit a steroid-induced ocular hypertensive response with no local complications. However, maintaining ocular hypertension increased by 50% for two months was not enough to detect changes in RGCs.

Keywords: Ocular hypertension, Retinal ganglion cell, Steroid-induced glaucoma

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Figure 1.

Dexamethasone instillation and induction of intraocular pressure (IOP). (A) Diagram for induction of IOP. Dexamethasone instillation began after baseline IOP check three times a day. After 4 weeks, in eyes with 50% elevated IOP than baseline, dexamethasone instillation was done 1 time a day for 4 weeks more. (B) IOP elevation in the mouse eyes at baseline and 8 weeks after dexamethasone instillation. CNT = control group; DEXA = dexamethason instillation group; RGC = retinal ganglion cell.

Figure 2.

Retinal ganglion cell (RGC) survival in control eyes and treated with dexamethasone eyes. Dexamethasone was instilled 3 times a day for 4 weeks in dexa group. After that, instilled once a day for 4 more weeks in eyes with elevated intraocular pressure (IOP) 50% than baseline. Retinal whole-mount immunohistochemistry for Brn3a in control group (A) and experimental group (B). (C) Quantitative analysis of RGC loss. Values are mean. There were no significant changes in RGC survival between control and dex- amethasone treated C57BL mice. Significant at p< 0.05. DEXA = dexamethason instillation group.

Figure 3.

Increased intraocular pressure (IOP) mediated apoptotic cell death. (A) There was no TUNEL-positive cells in the retina of control mice treated with artificial tears. (B) However, increased IOP retinas showed TUNEL-positive apoptotic cell death in the GCL and INL. Arrows: TUNEL-positive cell. TUNEL = terminal deoxynucleotidyl transferase dUTP nick end labeling; ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer.

Figure 4.

Increased intraocular pressure (IOP) induced apoptosis in dexamethasone instilled eyes. Dexamethasone was instilled 3 times a day for 4 weeks in experimental group. After that, instilled 1 time a day for 4 more weeks in eyes with elevated IOP 50% than baseline. Bax and pBad protein expression significantly increased in retina treated with dexamethasone. Values are mean. Significant at ^*p < 0.05. CNT = control group; DEXA = dexamethason instillation group.

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