Abstract
Purpose :
The DBA/2J (D2) mouse strain is widely used as a model for glaucoma. We compared the D2 and DBA/2J-Gpnmb+/SjJ (D2G) mouse strains to determine the relative roles of age-related changes in IOP and corneal pathology on visual dysfunction in the D2 mouse model of glaucoma. D2G mice are genetically identical to D2 mice with the exception of a normally functioning Gpnmb gene resulting in a lack of iris pigment dispersion and the absence of IOP elevation and glaucomatous neuropathy.
Methods :
IOP, visual acuity (VA) and corneal calcification were studied in D2 and D2G mice. IOP and VA were monitored over a 12-month period using tonometry and behavioral measures of the optomotor reflex. At 6, 9 and 12 months, corneas from each group were examined using confocal microscopy to measure the intensity, thickness and size of calcified regions.
Results :
D2 mice developed elevated IOP between 9 (13.53 ± 0.88 mmHg) and 12 months of age (23.53 ± 1.72 mmHg), but D2G mice did not (12.34 ± 0.33 mmHg at 9 and 13.8 ± 0.47 mmHg at 12 months). Corneal calcification was found in 46.4% of D2 eyes and 56.7% of D2G eyes at 6 months (P = 0.323), 52.5% and 52.6% at 9 months (P = 0.991) and 83.3% and 60.0% at 12 months (P = 0.1113). When comparing 9 and 12 month-old mice with calcification, D2 mice demonstrated an increase in calcification thickness (P = 0.005) and D2G mice demonstrated increases in calcification intensity (P = 0.006) and thickness (P = 0.036). At 12 months of age, D2 mice with corneal calcification had greater mean IOP (25.38 ± 1.85 mmHg) than D2 mice without corneal calcification (17.5 ± 2.53 mmHg; P = 0.048). No difference in IOP was observed between D2G mice with and without calcification at any age. Calcification thickness correlated positively with IOP (r = 0.415, P = 0.004) and negatively with visual acuity (r = -0.451, P = 0.014) in D2 but not D2G mice.
Conclusions :
Corneal calcification may affect noninvasive IOP measurements and visual function in D2 mice. While ocular hypertension secondary to iris pigment dispersion causes visual dysfunction, corneal abnormalities, such as corneal calcification, should be considered as potentially confounding factors for the assessment of vision loss in D2 mice.
This is a 2021 ARVO Annual Meeting abstract.