Mouse Models for the Analysis of Myopia: An Analysis of Variation in Eye Size of Adult Mice

Abstract

To assess the relative importance of genetic and environmental factors that modulate eye growth, eyes, lenses, and retinas of 507 mice belonging to 50 strains were measured. Mice of both sexes and a wide range of ages (27 to 526 days) were perfused for electron microscopy and eyes, lenses, and retinas were dissected and measured. Our uniform fixation protocol was shown to cause a weight loss of 4 to 6%. Multiple linear regression methods were used to explore relations between eye and lens weight, retinal area, age, sex, body and brain weight, and retinal ganglion cell number. The eye and lens of mice continue to grow long after sexual maturity is reached at 40 to 60 days of age. The pace of growth matches the logarithm of age. Despite their smaller bodies, females have eyes as large as those of males. The correlation of eye weight to brain weight is remarkably low (r = 0.19), whereas that to retinal area is high (r = 0.86). Surprisingly, the correlation between lens weight and the size of the posterior segment (eye minus lens weight) is only 0.5 to 0.6, and ratios of these parameters are highly variable. Heritability of all traits is between 25 to 50%. The continued growth of eyes in adult mice provides an excellent system to test effects of genetic and molecular manipulations on the development and treatment of myopia. Heritability is sufficiently high to map genes that specifically modulate growth of different parts of the eye.