Abstract
Age-related changes to the balance between the pressure inside the eye (intraocular pressure, IOP) and the pressure inside the brain (intracranial pressure, ICP) can modify the risk of glaucoma. In this study, we consider whether the optic nerve in older rat eyes is more susceptible to acute IOP and ICP modification. We systematically manipulate both ICP and IOP and quantify their effects on ganglion cell function (electroretinography, ERG), optic nerve structure (optical coherence tomography, OCT) and retinal blood flow (Doppler OCT). We show that ganglion cell function in older eyes was more susceptible to a higher optic nerve pressure difference (ONPD = IOP – ICP). This age-related susceptibility could not be explained by poorer blood flow with elevated ONPD. Rather, as ONPD increased the retinal nerve fibre layer showed greater compression, and the retinal surface showed less deformation in older eyes. Our data suggest that age-related changes to connective tissues in and around the rat optic nerve make it less flexible, which may result in greater strain on ganglion cell axons. This may account for greater functional susceptibility to higher optic nerve pressure differences in older rat eyes. Further studies in a species with a well-developed lamina cribrosa are needed to determine the clinical importance of these observations.
Highlights
Of the documented risk factors for glaucoma, ageing is perhaps the most robust
In agreement with their data, we showed in rodents, a species lacking a collagenous lamina cribrosa, that low and high intracranial pressure (ICP), increase and decrease intraocular pressure (IOP)-induced tissue deformation and compression, respectively[13]
Higher IOP levels lead to attenuation of the scotopic threshold response (STR) in both 3 month and 18 month old rats
Summary
Of the documented risk factors for glaucoma, ageing is perhaps the most robust. Aside from higher intraocular pressure (IOP), older age is the only other factor consistently and independently associated with increased risk of glaucoma development[1] and progression of visual field loss[2]. Morgan et al.[12] observed in canine eyes that small changes in ICP can substantially change the shape of the optic nerve In agreement with their data, we showed in rodents, a species lacking a collagenous lamina cribrosa, that low and high ICP, increase and decrease IOP-induced tissue deformation and compression, respectively[13]. We consider this hypothesis by comparing the effects of IOP elevation at low, normal and high ICP levels, on retinal function (electroretinography, ERG) and structure (optical coherence tomography, OCT) in 3 and 18 month old rats (equivalent to 10–15 and 45–50 human years[28], respectively) We related these functional and structural outcomes to a measure of inner retinal blood flow (Doppler OCT), in order to define vascular and mechanical contributions to age-related ganglion cell susceptibility to stress
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