Quantification of deficits in spatial visual function of mouse models for glaucoma

Abstract

Purpose: DBA/2J mice are a standard preclinical glaucoma model, which spontaneously developed mutations resulting in chronic age-related pigmentary glaucoma. The goals of this study were to identify the degree of visual impairment in DBA/2J mice before and after disease onset by quantifying the optokinetic reflex responses and to compare them to the less-researched strain of DBA/2NHsd mice.

Methods: Visual performance was measured in healthy, nonglaucomatous, and glaucomatous male DBA/2NHsd or DBA/2J mice using a visuospatial testing box. The optokinetic reflex resulting in optomotor head tracking was manually detected. Measured threshold levels equate to the maximum contrast or spatial frequency the mouse responds to. Intraocular pressure (IOP) was measured by applanation tonometry.

Results: IOP increased with age in both DBA/2J and DBA/2NHsd mice and was not different between the two substrains. Both visual acuity and ability to detect contrast decreased significantly, and similarly with age in both substrains. However, DBA/2NHsd had poorer visual acuity even at a younger age compared to age-matched DBA/2J mice.

Conclusions: Both DBA/2J and DBA/2NHsd mice show a progressive glaucomatous phenotype of age-related increases in IOP and loss of visual acuity and contrast sensitivity when compared to other inbred or outbred strains. Given the similar increases in IOP and contrast sensitivity threshold and loss of visual acuity between these two DBA/2 substrains, we also conclude that DBA/2NHsd mice are a suitable alternative model for pigmentary glaucoma.

Figure 1.

DBA/2J and DBA/2NHsd sub-strains had a similar age-related increase in IOP. Column graph showing IOP measurements in (A) combined (average of left and right) eye or (B) between the left and right eye of 6-week-old and 8-month-old male DBA/2J or DBA/2NHsd mice. Mean values ± SE, n = 5 for each group, *P < 0.05, **P < 0.01. Data were statistically analyzed using a one-way ANOVA with a Bonferroni post-test.

Figure 2.

Visual acuity was poorer in DBA/2NHsd compared to age-matched DBA/2J mice. Column graph showing visual acuity in (A) combined (average of left and right) eye or (B) between the left and right eye of 6-week-old and 8-month-old male DBA/2J or DBA/2NHsd mice. Mean values ± SE, *P < 0.05, **P < 0.01, ***P < 0.001. Data were statistically analyzed using a one-way ANOVA with a Bonferroni post-test.

Figure 3.

Contrast sensitivity thresholds were similar in DBA/2NHsd compared to age-matched DBA/2J mice. Column graph showing contrast sensitivity thresholds in (A) combined (average of left and right) eye or (B) between the left and right eye of 6-week-old and 8-month-old male DBA/2J or DBA/2NHsd mice. Mean values ± SE, ***P < 0.001. Data were statistically analyzed using a one-way ANOVA with a Bonferroni post-test.

Figure 4.

Strong correlation between age-related increases in IOP and attenuated visuospatial performance in both DBA/2 substrains. Visual acuity in the two DBA/2 substrains had a strong negative correlation with contrast sensitivity thresholds. Scatter graphs showing the statistical correlation between (A) visual acuity and IOP, (B) contrast sensitivity thresholds and IOP, or (C) contrast sensitivity threshold and visual acuity in 6-week-old or 8-month-old male DBA/2J or DBA/2NHsd mice. Data were statistically analyzed using a Pearson product-moment correlation coefficient (r) in order to evaluate the strength of the association between groups.