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Ayumi Nakagawa, Osamu Sakai, Hideki Tokushige, Takashi Fujishiro, Makoto Aihara; Development and analysis of a new rat glaucoma model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2523.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is mainly caused by glaucomatous optic neuropathy (GON) characterized by structural and functional damages, resulting in progressive loss of retinal ganglion cells (RGCs). Several animal glaucoma models based on increasing intraocular pressure (IOP) have been developed, however, it is difficult to obtain the consistent animal model with long-lasting IOP elevation. In addition, these models cannot be completely extrapolated to the properties of the complex pathogenesis of GON. In this study, we tried to establish a novel rat glaucoma model which achieved long-lasting IOP elevation with glaucomatous damage.
Conjunctival fibroblasts isolated from Sprague-Dawley rat eyes were cultured and injected into rat anterior chamber. IOP was measured using TonoLab® for 28 days. The changes of anterior and posterior segments were analyzed histologically. The numbers of RGCs labeled with brn3a in the flat-mounted retina were measured using image visualization software. The rate of RGC death was defined as the percentage of the decreased number of cells in the cell injected eye against the contralateral control eye of same animal. All these histological analyses were performed at 28 days after cell injection.
The IOP started to elevate 3 or 7 days after cell injection and it sustained higher than that of the contralateral control eyes until 28 days. The mean IOP after 28 days was 31.4±10.5 mmHg in cell injected eyes (n=6), while that of control eyes was 13.6±2.6 mmHg (n=6). The size of eyes gradually expanded and cell accumulation was observed in anterior chamber. Histological analysis of anterior sections showed that the angle of the cell injected eyes was completely occluded. Enlargement of optic nerve head cupping was also observed in the cell injected eyes. Cell injection induced activation of Müller glial cells as indicated by increased glial fibrillary acidic protein (GFAP) expression. The rate of RGC death in cell injected eyes was 61.4%±33.7% (n=6, P<0.05, paired one-sided t-test compared with control group).
We developed a valuably rat chronic ocular hypertension model induced by conjunctival fibroblasts injection. This model showed glaucomatous pathology such as enlargement of optic nerve head cupping and RGC loss. It would provide valuable information about the pathogenic mechanism of glaucoma and be also useful for evaluation of neuroprotective drugs.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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