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Uttio Roy Chowdhury, Bradley H Holman, Michael P Fautsch; Effect of low intracranial pressure on optic neuronal health in an experimental rat model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4131.
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© ARVO (1962-2015); The Authors (2016-present)
Intracranial pressure (ICP) has recently gained importance as a risk factor for glaucomatous neuropathies. We have developed a rat intraventricular cannula (IVC) model which allows lowering and real time monitoring of ICP for extended periods of time. The purpose of this study was to evaluate the health of retinal ganglion cells (RGC) and optic nerve axons following long term lowering of ICP.
Stainless steel cannulae (20 gauge) were surgically implanted in Brown Norway rats (n=3, retired breeders, age >8 months, weight >300 g). Through a flexible metal tether, the cannula was connected with PE60 tubing to a 3 way stopcock and a pressure transducer. A syringe column containing artificial cerebrospinal fluid (CSF) was attached in parallel. ICP was reduced by lowering the syringe column below head level in 1-2 cm increments. Flat mounted retinas were stained and RGCs counted and averaged from 12 specific predetermined regions across 4 quadrants. Optic nerve axons were counted and averaged from 3 separate toluidine blue stained 0.5 µm plastic sections of optic nerve head at 1 mm beyond the globe. All values were compared to either a normal rat or a sham control, where the syringe column was maintained at head level.
ICP was reduced by 53.7 ± 3.3% for approximately 60 days. Reduction of ICP was well tolerated by all rats with no apparent discomfort or weight loss. Experimentally lowered ICP caused significant decrease in RGC number when compared to normal (OD: 15.8 ± 21.9%, OS: 21.2 ± 25.7% reduction, p<0.05) or sham control (OD: 36.8 ± 22.8%, OS: 28.3 ± 19.1% reduction, p<0.05). This reduction was also reflected in a lowered axonal density compared to normal (OD: 24.5 ± 11.7%, OS: 26.8 ± 10.0% reduction) or sham control (OD: 33.2 ± 3.0%, OS: 14.2 ± 14.4% reduction). In rats where ICP was lowered, fibrotic and compressed axons were observed in the optic nerve.
Sustained ICP reduction caused a decrease in RGCs and optic nerve axons in the rat IVC model. The rat IVC model can be an effective tool to investigate and establish the role of ICP as an important contributory factor in the pathophysiology of glaucoma.
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