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R. Naskar, S. Thanos; Description of a New Rat Model for Chronic Glaucoma . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3324.
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Purpose: The objective of the current study was to characterize and describe a novel rat model of chronic glaucoma derived from the Royal College of Surgeons (RCS) strain. Methods: Gross alterations in the size of the globes, which lead us to initially study this strain, were documented photographically. Intraocular pressure (IOP) was measured with a TonoPen. Retinal ganglion cells (RGCs) were characterized and quantified on flat mounts after retrograde labeling with the fluorescent dye 4-Di-10 ASP. The optic nerve head was examined fundoscopically as well as on histological sections. Histology and immunocytochemistry were carried out on paraffin and cryostat sections respectively. The expression of certain genes was examined at the mRNA level using RT-PCR. Results: The globes of the rats were either unilaterally or bilaterally enlarged and exhibited traits typical of glaucoma. This enlargement developed spontaneously and was not the result of experimental manipulation. Intraocular pressure was observed to increase with age attaining values of 39.0 ± 5.8 at 18 months. Photoreceptor degeneration was documented and is a common feature of the RCS strain. The optic nerve head was excavated and RGC number decreased over time, with 38% remaining at 18 months of age. The most remarkable feature was the hypertrophied ciliary body. Certain genes such as glial fibrillary acidic protein (GFAP), the glutamate transporter (EAAC1), Signal Transduction and Activators of Transcription (STAT-3 & -6) were up-regulated over time at the mRNA level. Immunocytochemistry confirmed the up-regulation of GFAP. Decrease in Thy-1 positive RGCs confirmed the data obtained from flat mounts. Calbindin and parvalbumin positive cells indicated that horizontal and amacrine cells remained unaffected in these eyes. Conclusions: Here we present a strain of RCS rat that spontaneously develops glaucoma. In these animals IOP increases with age and remains consistently elevated. The optic nerve head is excavated and ganglion cells undergo cell death as in human glaucoma The structural anomaly is the hypertrophied ciliary body. This model allows characterization at various levels with the possibility of testing pharmacologic agents for the treatment of glaucoma in humans.
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