Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USC Roski Eye Institute, Los Angeles, CA, USA.
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.
Exp Eye Res. 2021 Apr;205:108480. doi: 10.1016/j.exer.2021.108480. Epub 2021 Feb 2.
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 (DO), the rate of oxygen extraction from the retinal circulation for metabolism (MO), 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 and O) were measured using phosphorescence lifetime imaging. Total retinal blood flow (TRBF) was determined by fluorescence and red-free imaging. DO and MO were determined as TRBF × O and TRBF × (O-O), respectively. OEF was calculated as MO/DO. The thickness of individual retinal layers was measured from histology sections and inner retina (IR) and total retina (TR) thickness were calculated. TRBF, DO and MO 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 DO were lower at 3-weeks of age compared to 12-weeks of age (P ≤ 0.01), while MO 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). MO 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.
视网膜变性 1（rd1）小鼠是一种成熟的遗传性视网膜变性模型，表现出光感受器变性和视网膜血管损伤。本研究的目的是确定 rd1 小鼠从视网膜循环中输送氧气的速度（DO）、从视网膜循环中提取用于代谢的氧气速度（MO）和氧提取分数（OEF）的变化。该研究共在 3 周和 12 周龄的 18 只野生型（WT）和 10 只 rd1 小鼠中进行。使用磷光寿命成像测量视网膜动脉和静脉氧含量（O 和 O）。通过荧光和无红光成像确定总视网膜血流量（TRBF）。DO 和 MO 分别确定为 TRBF×O 和 TRBF×（O-O）。OEF 计算为 MO/DO。从组织学切片测量各个视网膜层的厚度，并计算内视网膜（IR）和总视网膜（TR）的厚度。与 WT 小鼠相比，rd1 小鼠的 TRBF、DO 和 MO 较低（P≤0.001），而 rd1 和 WT 小鼠之间的 OEF 没有显著差异（P=0.4）。与 12 周龄相比，3 周龄时 TRBF 和 DO 较低（P≤0.01），而 MO 在不同年龄组之间无显著差异（P=0.4），并且 3 周龄时 OEF 高于 12 周龄（P=0.003）。此外，与同龄 WT 小鼠和 3 周龄 rd1 小鼠相比，12 周龄 rd1 小鼠的外和内视网膜细胞层厚度降低（P≤0.02）。MO 与 IR 和 TR 厚度直接相关（R≥0.50；P≤0.03，N=20）。研究结果表明，视网膜循环供应的氧气速度降低，提取用于代谢的氧气减少与 rd1 小鼠的视网膜细胞层变薄有关。
