Inner Retinal Oxygen Delivery and Metabolism in Diabetic Mice

Abstract

Purpose: The spontaneously diabetic Ins2(Akita) mouse develops changes resembling early diabetic retinopathy with abnormalities such as leukostasis, increased vascular permeability, increased apoptosis, and reduced ganglion cells occurring as early as 12 weeks of age. These alterations may impair energy utilization by the retinal tissue. The purpose of this study is to report measurements of inner retinal oxygen delivery (DO₂) and metabolism (MO₂) in the Ins2(Akita) mouse.

Methods: Retinal vascular oxygen tension (PO₂) and blood flow imaging were performed in one eye of age-matched diabetic Ins2(Akita) (age: 12 ± 1 weeks, N = 7) and healthy C57BL/6J wild type (age: 12 weeks, N = 5) mice. Retinal vascular PO₂ was measured in major retinal arteries (PO_2A) and veins (PO_2V) by phosphorescence lifetime section imaging. Arterial (O_2A) and venous (O_2V) oxygen contents were calculated from these measurements using the mouse hemoglobin dissociation curve. Venous blood velocity (V) and diameter (D) were determined by fluorescent microsphere imaging and fluorescein angiography, respectively, allowing calculation of total venous blood flow (F). Inner retinal DO₂ and MO₂ were calculated from the products of F and O_2A and F and O_2A - O_2V, respectively. Student’s t-test was used to compare measurements between Ins2(Akita) and wild type mice.

Results: Blood glucose levels in Ins2(Akita) mice (397 ± 109 mg/dL, N = 5) were significantly elevated compared to measurements in wild type mice (156 ± 23 mg/dL, N = 5) (p = 0.001). Body weight of Ins2(Akita) mice (23 ± 3 g) was significantly lower compared to that of wild type mice (30 ± 2 g) (p < 0.001). PO_2A, PO_2V, O_2A, and O_2v measurements were not significantly different between Ins2(Akita) and wild type mice (p ≥ 0.08). Likewise, venous D, V, and F measurements were comparable between Ins2(Akita) and wild type mice (p ≥ 0.46). Inner retinal DO₂ in Ins2(Akita) (91 ± 25 nL O₂/min) and wild type (112 ± 19 nL O₂/min) mice were similar (p = 0.14). Likewise, inner retinal MO₂ in Ins2(Akita) (64 ± 28 nL O₂/min) and wild type (80 ± 22 nL O₂/min) mice were similar (p =0.31).

Conclusions: At 12 weeks of age, inner retinal oxygen delivery and metabolism were similar between diabetic and non-diabetic mice, suggesting vascular or neural alterations due to diabetes had a minimal effect on retinal oxygen utilization. These findings may have implications for understanding retinal pathophysiology in early stages of diabetes.