RESUMEN
Aniridia is a panocular condition characterized by a partial or complete loss of the iris. It manifests various developmental deficits in both the anterior and posterior segments of the eye, leading to a progressive vision loss. The homeobox gene PAX6 plays an important role in ocular development and mutations of PAX6 have been the main causative factors for aniridia. In this study, we assessed how Pax6-haploinsufficiency affects retinal morphology and vision of Pax6Sey mice using in vivo and ex vivo metrics. We used mice of C57BL/6 and 129S1/Svlmj genetic backgrounds to examine the variable severity of symptoms as reflected in human aniridia patients. Elevated intraocular pressure (IOP) was observed in Pax6Sey mice starting from post-natal day 20 (P20). Correspondingly, visual acuity showed a steady age-dependent decline in Pax6Sey mice, though these phenotypes were less severe in the 129S1/Svlmj mice. Local retinal damage with layer disorganization was assessed at P30 and P80 in the Pax6Sey mice. Interestingly, we also observed a greater number of activated Iba1+ microglia and GFAP + astrocytes in the Pax6Sey mice than in littermate controls, suggesting a possible neuroinflammatory response to Pax6 deficiencies.
Asunto(s)
Aniridia , Microftalmía , Humanos , Ratones , Animales , Factor de Transcripción PAX6/genética , Factores de Transcripción Paired Box/genética , Enfermedades Neuroinflamatorias , Ratones Endogámicos C57BL , Microftalmía/genética , Aniridia/genética , Proteínas de Homeodominio/genética , Proteínas del Ojo/genéticaRESUMEN
In recent years, in vivo retinal imaging, which provides non-invasive, real-time, and longitudinal information about biological systems and processes, has been increasingly applied to obtain an objective assessment of neural damage in eye diseases. Ex vivo confocal imaging of the same retina is often necessary to validate the in vivo findings especially in animal research. In this study, we demonstrated a method for aligning an ex vivo confocal image of the mouse retina with its in vivo images. A new clinical-ready imaging technology called visible light optical coherence tomography fibergraphy (vis-OCTF) was applied to acquire in vivo images of the mouse retina. We then performed the confocal imaging of the same retina as the "gold standard" to validate the in vivo vis-OCTF images. This study not only enables further investigation of the molecular and cellular mechanisms but also establishes a foundation for a sensitive and objective evaluation of neural damage in vivo.