Mild Intraocular Pressure Elevation in Mice Reveals Distinct Retinal Ganglion Cell Functional Thresholds and Pressure-Dependent Properties

Elevation of intraocular pressure (IOP) causes retinal ganglion cell (RGC) dysfunction and death and is a major risk factor for glaucoma. We used a bead injection technique to increase IOP in mice of both genders by an average of similar to 3 mmHg for 2 weeks. This level of IOP elevation was lower than that achieved in other studies, which allowed for the study of subtle IOP effects. We used multielectrode array recordings to determine the cellular responses of RGCs exposed to this mild degree of IOP elevation. We found that RGC photopic receptive field (RF) center size and whole-field RGC firing rates were unaffected by IOP elevation. In contrast, we found that the temporal properties of RGC photopic responses in the RF center were accelerated, particularly in ON sustained cells. We also detected a loss of antagonistic surround in several RGC subtypes. Finally, spontaneous firing rate, interspike interval variance, and contrast sensitivity were altered according to the magnitude of IOP exposure and also displayed an IOP-dependent effect. Together, these results suggest that individual RGC physiologic parameters have unique IOP-related functional thresholds that exist concurrently and change following IOP elevation according to specific patterns. Furthermore, even subtle IOP elevation can impart profound changes in RGC function, which in some cases may occur in an IOP-dependent manner. This system of overlapping functional thresholds likely underlies the complex effects of elevated IOP on the retina.