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J. L. Son, I. Soto, E. Oglesby, M. E. Pease, H. A. Quigley, N. Marsh-Armstrong; Monitoring Glaucoma Progression in the Translimbal Trabecular Laser Photocoagulation Rat Model Using Molecular Markers. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2764.
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Analyses using the retinal ganglion cell (RGC) specific marker gamma synuclein (Sncg) mRNA and phosphorylated neurofilament (pNF) have previously shown the loss of RGCs in the DBA/2J mouse glaucoma model to be sectorial and involve the loss of axons before cell bodies. Within the DBA/2J optic nerve (ON), the loss of axons is accompanied by an increase in the number and reactivity of astrocytes but only a modest loss of oligodendrocytes. In order to determine whether these findings apply to different glaucoma animal models, a comparable analysis was performed on the rat translimbal laser photocoagulation model.
High intraocular pressure (IOP) was induced in Wistar rats using translimbal trabecular laser photocoagulation. Retinas and ONs were dissected from 10 rats at 10 days (d) and 10 rats at 29 d after laser treatment. In situ hybridization and immunohistochemistry were performed on whole-mounted retinas and sectioned ONs. Riboprobes such as Sncg for RGCs, vimentin for astrocytes and proteolipid protein (PLP) for oligodendrocytes as well as pNF antibodies were used to characterize indices of disease progression in retina and ON. Quantifications were performed using light and fluorescence microscopy and novel scripts written for IPlab.
In glaucoma retinas, the loss of RGCs was sectorial with approximately 35% loss of cells at 10d and 75% at 29d. RGC loss coincided with increased number of RGCs with somatic accumulation of pNF: from ~ 0 in controls to ~ 5,000 at 10d and ~ 2,000 at 29d. Within the ON, loss of axons was characterized by increased expression of vimentin by 10d and a decrease in PLP expression and oligodendrocytes only at 29d post-laser treatment.
The pattern of RGC loss is similar in DBA/2J mice and rat translimbal laser models. The molecular changes in the ON correlate well with retina changes and are suggestive of an early astrocyte and late oligodendrocyte response. We therefore conclude that these molecular markers show similar disease progression in the different rodent glaucoma models.
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