Abstract
The spaceflight-associated neuro-ocular syndrome (SANS), which may present after prolonged exposure to microgravity, is thought to occur due to elevated intracranial pressure (ICP). Intracranial pressure interacts with intraocular pressure (IOP) to define the translaminar pressure difference (TLPD; IOP−ICP). We combined inducible models of ICP and IOP elevation in mice to interrogate the relationships among ICP, IOP, and TLPD, and to determine if IOP elevation could mitigate the phenotypes typically caused by elevated ICP and thereby serve as a countermeasure for SANS. Ten C57BL6J mice of both genders underwent experimental elevation of ICP via infusion of artificial cerebrospinal fluid into the subarachnoid space. One eye also underwent experimental elevation of IOP using the bead injection model. Intraocular pressure and ICP were monitored for 2 weeks. Optokinetic-based contrast sensitivity was measured at baseline and after 2 weeks, and post-mortem studies of optic nerve and retina anatomy were performed. Photopic contrast sensitivity was reduced more in IOP elevated than control eyes. Scotopic contrast sensitivity was reduced similarly in IOP elevated and control eyes. However, the pattern of scotopic vision loss was not uniform in IOP elevated eyes; there was minimal loss in eyes that most closely approximated the normal TLPD. Optic nerve axon loss, increased optic nerve disorganization, and retinal ganglion cell loss all occurred similarly between IOP elevated and control eyes. Elevation of IOP in eyes with elevated ICP may counterbalance some effects on vision loss but exacerbate others, suggesting complex relationships among IOP, ICP, and TLPD.
Highlights
Retinal ganglion cells (RGCs) are the obligate output neuron of the mammalian retina and their axons are the primary constituents of the optic nerve
Intracranial pressure elevation was maintained for 2 weeks and intracranial pressure (ICP) increased from an average baseline level of 5.44 ± 1.24 mmHg to an average experimental level of 18.02 ± 1.40 (p < 0.001; Fig. 2a)
The elevation of intraocular pressure (IOP) in only one eye allowed us to test if elevation of IOP was sufficient to mitigate phenotypes caused by elevated ICP, and to compare to contralateral control eyes of the same animal
Summary
Retinal ganglion cells (RGCs) are the obligate output neuron of the mammalian retina and their axons are the primary constituents of the optic nerve. The optic nerve exits the eye posteriorly and travels to the brain where RGC axons synapse on higher order neurons. Along this path, two primary forces influence RGC axons: the intraocular pressure (IOP) inside the eye and at the anterior optic nerve head, and the intracranial pressure (ICP) at the posterior optic nerve head and along the course of the optic nerve[1,2,3,4]. SANS, occurs when ICP is elevated but IOP is normal and the TLPD is reduced, and results in optic disc swelling and a variety of changes in vision which may be asymmetric[6,8,9]. Correction of ICP, IOP, or TLPD imbalances by manipulation of one or both pressures could alleviate some disease symptoms
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