Abstract
Purpose :
Fluorescence lifetime (FLT) is a fluorophore-specific property and cellular FLT may be influenced by cell metabolic states. Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a new method that enabled the measurement of FLT of ocular fundus. The purpose of this study was to investigate the fundus FLT of mouse models of retinal degeneration with FLIO.
Methods :
Two mouse models of age-related macular degeneration (AMD), apolipoprotein E (ApoE) deficient mice (ApoE-/-) and nuclear factor erythroid 2-related factor 2 (NRF2) deficient mice (Nrf2-/-), and wild type mice (control; C57BL/6J) were investigated monthly from 3 months old (24 mice per strain). Under general anesthesia, slit lamp Ophthalmoscopy, FLIO, optical coherence tomography (OCT) and fundus photography were conducted. The mice were euthanized either at 6 months old or 11 months old. The blood plasma was collected to examine the level of total antioxidant capacity (TAC). The frozen sections of the enucleated eyes were assessed with lipid stainings (Oil Red O).
Results :
AMD-like pathological findings (e.g. drusen) were observed after 7 months old in some mice of AMD models. The mean FLT (τm) was generally shortened with age in all groups. Both AMD models showed significantly shorter τm than the control at 4 months old. After that, τm of ApoE-/- mice was further shortened to a larger extent than the control until 11 months old in both spectral channels, whereas Nrf2-/- mice showed an apparently prolonged τm in the long spectrum channel. The strongest lipid staining of the Bruch’s membrane was observed in ApoE-/- mice at 11 months old. The blood TAC of ApoE-/- mice was significantly higher than the control at 6 and 11 months. Nrf2-/- mice showed higher TAC at 6 months old than control, but then decreased and no more difference was found from the control group at 11 months old.
Conclusions :
Both mouse models of AMD showed a temporarily shorter fundus FLT than the wild type at a very early time point, presumably owing to the metabolic activation due to stress. After that, however, the fundus FLT of these two strains progressed totally differently over time. The systemic antioxidant capacity could be associated with this difference. These results strongly suggest that FLIO may indicate early changes of metabolic and redox states of the retina prior to the onset of degenerative retinal disorders.
This is a 2021 ARVO Annual Meeting abstract.