Retinal degeneration increases susceptibility to myopia in mice

Purpose: Retinal diseases are often associated with refractive errors, suggesting the importance of normal retinal signaling during emmetropization. For instance, retinitis pigmentosa, a disease characterized by severe photoreceptor degeneration, is associated with myopia; however, the underlying link between these conditions is not known. This study examines the influence of photoreceptor degeneration on refractive development by testing two mouse models of retinitis pigmentosa under normal and form deprivation visual conditions. Dopamine, a potential stop signal for refractive eye growth, was assessed as a potential underlying mechanism. Methods: Refractive eye growth in mice that were homozygous for a mutation in Pde6b, Pde6b(rd1/rd1) (rd1), or Pde6b(rd10/rd10) (rd10) was measured weekly from 4 to 12 weeks of age and compared to age- matched wild- type (WT) mice. Refractive error was measured using an eccentric infrared photorefractor, and axial length was measured with partial coherence interferometry or spectral domain ocular coherence tomography. A cohort of mice received head- mounted diffuser goggles to induce form deprivation from 4 to 6 weeks of age. Dopamine and 3,4- dihydroxyphenylacetic acid (DOPAC) levels were measured with high- performance liquid chromatography in each strain after exposure to normal or form deprivation conditions. Results: The rd1 and rd10 mice had significantly greater hyperopia relative to the WT controls throughout normal development; however, axial length became significantly longer only in WT mice starting at 7 weeks of age. After 2 weeks of form deprivation, the rd1 and rd10 mice demonstrated a faster and larger myopic shift (-6.14 +/- 0.62 and -7.38 +/- 1.46 diopter, respectively) compared to the WT mice (-2.41 +/- 0.47 diopter). Under normal visual conditions, the DOPAC levels and DOPAC/dopamine ratios, a measure of dopamine turnover, were significantly lower in the rd1 and rd10 mice compared to the WT mice, while the dopamine levels were similar or higher than WT in the rd10 mice. Lower basal levels of DOPAC were highly correlated with increasing myopic shifts. Conclusions: Refractive development under normal visual conditions was disrupted toward greater hyperopia from 4 to 12 weeks of age in these photoreceptor degeneration models, despite significantly lower DOPAC levels. However, the retinal degeneration models with low basal levels of DOPAC had increased susceptibility to form deprivation myopia. These results indicate that photoreceptor degeneration may alter dopamine metabolism, leading to increased susceptibility to myopia with an environmental visual challenge.