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Bing Li, Erica Perez, David Cantu-Crouch, Yu Wang, Shutong Cao, Laura Klekar, Jamie Raines, David Earnest, Richard Ornberg, Ganesh Prasanna; Prednisolone Induces Time- And Dose-dependent Ocular Hypertension In Rats. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1970.
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To develop a simple steroid-induced ocular hypertension model in rats.
Prednisolone pellets (0.1 mg, 1.5 mg, 2 x10 mg and 25 mg) were implanted subcutaneously in Male Lewis rats and intraocular pressure (IOP) readings were taken in a masked manner using a TonoLab rebound tonometer. Body weights were monitored weekly. Correlation of plasma and aqueous humor (AH) steroid levels and IOP elevation were made following implantation of pellets (n=8 rats in each group). Ultrastructural changes to the anterior chamber angle and trabecular meshwork (TM) and expression of select protein markers were assessed using a) light microscopy, b) electron microscopy and c) immunohistochemistry of α-smooth muscle actin (α-SMA), collagen IV and collagen VI.
Prednisolone levels in plasma and AH increased in a dose-dependent matter. No prednisone pellet treated group (except 50 mg) showed >20% weight loss. Compared with baseline IOP and that for placebo rats, rats implanted with prednisolone pellets (2 x 10 mg and 25 mg), exhibited significant IOP elevation (15-28%; p<0.001) starting on weeks 2-3 post-implantation and was maintained till the end of pellet release (21 or 60 days). In prednisolone implanted rats, topical ocular dosing with Xalatan® caused a biphasic response in IOP, with a transient 25% increase at 1 hour and 21% decrease at 24 hour post-dose. When compared to placebo rats, prednisolone-implanted rats demonstrated ultrastructural changes to the TM consisting of more compact layering of TM lamellae and reduced intra-lamellar spaces due to thickened beams or matrix deposition. Schlemm’s canal (SC) appeared to be less prominent/ reduced in prednisolone rats. α-SMA immunolabeling was greatly increased (++) in the TM tissues in prednisolone-implanted rats (++ in 63-75% rats) compared to placebo rats (++ in 0-42% rats).
Prednisolone treatment elicits reproducible ocular hypertension in male Lewis rats. Ultrastructural changes in α-SMA are indicative of a steroid effect on TM as previously shown in human anterior chamber tissues (glaucomatous or steroid-treated) and maybe involved in resistance to AH outflow. IOP in prednisolone-implanted rats was responsive to topical dosing of a prostaglandin analog. Implanting pellets is a simple technique and less labor intensive than topical ocular dosing for delivering steroids over a long period of time. A prednisolone-induced model of ocular hypertension in rats could be useful for further investigations of the patho-mechanisms involved in glaucoma.
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