Abstract
Purpose :
Intraocular pressure (IOP) and intracranial pressure (ICP) are forces which oppose at the optic nerve head. Together they form the translaminar pressure difference (TLPD; IOP - ICP) which, when altered, can result in human disease. We combined inducible mouse models of IOP and ICP elevation to study the relationship between IOP and ICP.
Methods :
Ten C57BL6J mice of both genders (6 female, 4 male), aged 12 weeks, underwent experimental elevation of ICP. One eye underwent concomitant experimental elevation of IOP using the bead injection model and the other eye received saline injection and served as a control. For 2 weeks, ICP was measured daily and IOP was measured 2 times a week. Baseline measurements of optokinetic-based contrast sensitivity were taken prior to any pressure elevation and then again at the completion of the experiment. Electron microscopy of the optic nerve and immunohistochemistry of the retina were performed. Change in optokinetic response, axon count, and retinal cell counts were compared to physiological parameters such as ICP, IOP, TLPD, and change in TLPD.
Results :
The average magnitude of increase was greater for ICP than IOP, causing a reversal of the TLPD in most animals. Overall, contrast sensitivity was diminished more in bead injected eyes (0.33 log reduction for scotopic and 0.44 for photopic) than controls (0.19 for scotopic and 0.18 for photopic). However, contrast sensitivity loss was not uniform, and scotopic contrast sensitivity loss was minimal in eyes that most closely approximated the endogenous TLPD throughout the experiment, despite the elevation of both IOP and ICP. After ICP elevation, optic nerve axon counts were reduced and similar between groups (42,003 ± 4,559 axons/nerve for bead injected eyes, 37,983 ± 2,100 axons/nerve for saline injected eyes, p = 0.4689). Retinal ganglion cell loss was also reduced and similar between groups (1,924 ± 250 RGCs/mm^2 for saline injected eyes, 1,840 ± 301 RGCs/mm^2 for saline injected eyes, p = 0.75).
Conclusions :
Concomitant elevation of IOP did not further impact the optic nerve or RGC losses caused by ICP elevation. However IOP elevation did prevent contrast sensitivity loss caused by ICP elevation, but only in eyes in which the endogenous TLPD was maintained. This prevention of vision loss occurred despite marked anatomic abnormalities.
This is a 2020 ARVO Annual Meeting abstract.