Intermittent hypoxia associated with obstructive sleep apnea disrupts microvasculature networks in the mouse retina

Obstructive sleep apnea is prevalent in obese individuals and is associated with retinal vascular pathologies. Intermittent hypoxia (IH), associated with sleep apnea, and metabolic disorders, related to obesity, elevate levels of reactive oxygen species (ROS) which mediate retinal damage. While diet-induced dysfunction of the eye is well studied (i.e. diabetic retinopathy), effects of IH are far less understood. Furthermore, the interaction of these two factors to alter the retinal vasculature has not been evaluated. We hypothesized that smooth muscle cells (SMCs) and endothelial cells (ECs) of the retinal microvascular network are modified by IH to limit the area of vascular perfusion. To test the respective contributions of diet and IH to microvascular network remodeling, male mice were fed a high fat diet (HFD) or control diet (CD) for 26 weeks and exposed to IH (90 s cycles alternating between 21% F iO2 and 6% F iO2 for 12 hr/day) or sham (normoxic) conditions for the final 16 weeks of feeding. ROS production in the retina was evaluated using (DHE 10 μg/mL). Retinal ROS levels were significantly greater (p<0.05, n=5) following both HFD and IH individually, with no additive effect when HFD and IH were combined. SMC and EC networks were evaluated with anti-SMA actin antibody (1:500; Novus Biological NBP2-47699G) and lectin (1:200; Vector Laboratories, Isolectin-B4, DL-1208), respectively. Vascular network density of SMCs and ECs was determined by evaluating the area (%) of each cell type’s coverage in images (0.82 mm 2 ) from fixed (4% paraformaldehyde), flat-mounted retinas. Four regions/images were averaged to provide a single value for each retina. Arterial diameter was quantified in arteries originating from the optic disc, the subsequent branch arteries, and the terminal arterioles. Surprisingly, HFD had no significant effect on EC or SMC density. For both CD and HFD mice, IH led to a reduction in EC and SMC coverage (p<0.05, n=5). Consistently, IH led to a reduction in artery, branch artery, and terminal arteriole diameter in retinas from mice fed either diet, while HFD alone had no effect (p<0.05, n=5). We conclude that while both IH and HFD augment ROS production in the retina, IH has a far greater contribution to microvascular network disruption which may impair tissue perfusion. These findings provide unique insight into the role of IH in vascular dysfunction associated with sleep apnea-induced retinal pathology. NIH R01NS134690, R01HL166617 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.