Assessment of inner retinal oxygen metrics and thickness in a mouse model of inherited retinal degeneration

The retinal degeneration 1 (rd1) mouse is a well-established model of inherited retinal degeneration, displaying photoreceptor degeneration and retinal vasculature damage. The purpose of the current study was to determine alterations in the rate of oxygen delivery from retinal circulation (DO₂), the rate of oxygen extraction from the retinal circulation for metabolism (MO₂), and oxygen extraction fraction (OEF) in rd1 mice. The study was performed in a total of 18 wild type (WT) and 10 rd1 mice at both 3-weeks and 12-weeks of age. Retinal arterial and venous oxygen contents (O_2A and O_2V) were measured using phosphorescence lifetime imaging. Total retinal blood flow (TRBF) was determined by fluorescence and red-free imaging. DO₂ and MO₂ were determined as TRBF × O_2A and TRBF × (O_2A-O_2V), respectively. OEF was calculated as MO₂/DO₂. The thickness of individual retinal layers was measured from histology sections and inner retina (IR) and total retina (TR) thickness were calculated. TRBF, DO₂ and MO₂ were lower in rd1 mice compared to WT mice (P ≤ 0.001), whereas OEF was not significantly different between rd1 and WT mice (P = 0.4). TRBF and DO₂ were lower at 3-weeks of age compared to 12-weeks of age (P ≤ 0.01), while MO₂ was not significantly different between age groups (P = 0.4) and OEF was higher at 3-weeks of age compared to 12-weeks of age (P = 0.003). Additionally, the outer and inner retinal cell layer thicknesses were decreased in rd1 mice at 12-weeks of age compared to both age-matched WT mice and rd1 mice at 3-weeks of age (P ≤ 0.02). MO₂ was directly correlated with both IR and TR thickness (R ≥ 0.50; P ≤ 0.03, N = 20). The findings indicate that the rate oxygen is supplied by the retinal circulation is decreased and the reduction in oxygen extracted for metabolism is related to retinal cell layer thinning in rd1 mice.