Mouse Model With ON Pathway Defect Has Increased Susceptibility to Form Deprivation Myopia

Abstract

Abstract: : Purpose: Recent studies have shown that C57BL/6J mice respond to form deprivation with myopic shifts in refraction and increased axial length as demonstrated in many other species. The nob mouse is a model of the complete form of X–linked congenital stationary night blindness (CSNB1). This condition is associated with the absence of the ERG b–wave caused by a defect in the rod ON–pathway. In humans, CSNB1 is also associated with a high degree of myopia. While nob mice have been shown to have normal refractive development, we tested whether nob mice would have an increased susceptibility to form deprivation myopia, given their phenotypic similarities to CSNB1. Methods: Pigmented nob and wild–type C57BL/6J mice were fitted with monocular diffuser goggles at 28 days of age. Mice were refracted with an automated eccentric infrared photorefractor between 2 and 8 weeks post–goggling. Data from goggled eyes were compared to the opposite unmanipulated eyes as well to the eyes of age– and strain–matched ungoggled mice. Results: After only 2 weeks of diffusion, 100% of goggled nob eyes had already developed significant myopic shifts in refraction compared to unmanipulated and control eyes. At 4 weeks post–goggling the myopic shift measured in nob mice was 3X larger than that measured in C57BL/6 mice. After 8 weeks of diffusion, only 80% of the goggled C57BL/6 eyes had developed significant myopic shifts compared to control eyes. Conclusions: Nob mice develop larger and faster myopic shifts after form deprivation than C57BL/6J mice, suggesting an increased susceptibility to form deprivation myopia. Although nob mice have normal refractive development under standard visual conditions, the ON–pathway defect may potentiate the environmental influences that lead to abnormal refractive development.

Keywords: myopia • retina: distal (photoreceptors, horizontal cells, bipolar cells) • refractive error development