Contrast sensitivity is a sensitive readout of early pathological changes in chronic but not acute mouse models of ocular hypertension

Purpose : To understand whether spatial vision is associated with the early changes in retinal structure and functions in in acute and chronic ocular hypertension models.

Methods : Chronic ocular hypertension (OH) was induced by a single unilateral injection of 10 um diameter microbead into the anterior chamber. In contrast, acute ocular hypertension was induced unilaterally by retinal ischemia/reperfusion (I/R) injury with elevating IOP to 85 mmHg for 1 hour in mice. Electroretinogram of positive scotopic threshold response (pSTR) was measured, indicating retinal ganglion cell (RGC) functions. Optomotor response assays assessed contrast sensitivity (CS) and visual acuity (VA) thresholds. The ganglion cell complex's (GCC) thickness was measured by optical coherence tomography. RGC counts were acquired in retinal flat mounts immunolabelled by Brn3a. Assays were performed up to 8 weeks post-injury. T-test or One-way ANOVA was used for statistical analysis.

Results : Chronic and acute OH groups exhibited significant reductions in RGC density and pSTR amplitude (P<0.05) two weeks post-injury and onwards. In the chronic OH group, compared to the sham-treated group, we detected an early and significant reduction of contrast sensitivity at two weeks post-injury (P<0.05), while visual acuity was significantly reduced starting at six weeks post-injury (P<0.05). However, in the acute OH group, both CS and VA decreased substantially at two weeks post-injury (P<0.001). In the chronic OH group, GCC thickness reduced considerably at 6- and 8-weeks post-injury (P<0.05). On the contrary, in the acute OH group, GCC thickness was significantly increased at 2- and 4-weeks post-injury (P<0.05, P<0.01) that may be due to edema.

Conclusions : Contrast sensitivity is a sensitive marker to implicate the early pathological changes in mouse retina with microbead-induced chronic ocular hypertension. On the contrary, both contrast sensitivity and visual acuity showed a similar temporal profile of reduction after acute ocular hypertension.