ABSTRACT
Microglia play a role in the pathogenesis of many retinal diseases. Fundus spots in mice often correlate with the accumulation of activated subretinal microglia. Here we use a semiquantitative fundus spot scoring scale in combination with an unbiased, state-of-the-science forward genetics pipeline to identify causative associations between chemically induced mutations and fundus spot phenotypes. Among several associations, we focus on a missense mutation in Lipe linked to an increase in yellow fundus spots in C57BL/6J mice. Lipe-/- mice generated using CRISPR-Cas9 technology are found to develop accumulation of subretinal microglia, a retinal degeneration with decreased visual function, and an abnormal retinal lipid profile. We establish an indispensable role of Lipe in retinal/RPE lipid homeostasis and retinal health. Further studies using this new model will be aimed at determining how lipid dysregulation results in the activation of subretinal microglia and whether these microglia also play a role in the subsequent retinal degeneration.
Subject(s)
Retinal Degeneration , Animals , Mice , Disease Models, Animal , Genetic Testing , Lipids , Mice, Inbred C57BL , Retinal Degeneration/genetics , Retinal Degeneration/pathologyABSTRACT
Recent studies provide insights into the mechanisms by which Abelson non-receptor tyrosine kinases relay information from axon guidance and growth factor receptors to promote cytoskeletal rearrangements in developing neurons. Abelson non-receptor tyrosine kinases are also found in mature synapses, where their activities are required for optimal synaptic function.
