Retinal thickness and subnormal retinal oxygenation response in experimental diabetic retinopathy

PURPOSE. To test the hypothesis that subnormal retinal oxygenation response (Delta Po-2) found at 3 months of experimental diabetes is associated with cellular swelling and increased retinal thickness. METHODS. Two groups of animals were studied: control rats injected intraperitoneally with either 15% body weight of saline or distilled water (cellular swelling model) or with intravitreal N-methyl-D-aspartate (NMDA) and 3-month-old diabetic and age-matched control rats. Intraocular pressure and retinal thickness was assessed using an applanation tonometer or high-resolution MRI (23.4 mu m(2) in-plane). In separate studies, functional MRI was used to measure blood-retinal barrier (BRB) integrity after Gd-DTPA injection intravenously and retinal Delta Po-2 during carbogen provocation. RESULTS. Inner and total retinal thickness were lower (P < 0.05) after NMDA injection, not different (P > 0.05) between control, before and after saline injection and before distilled water injection, and supernormal (P < 0.05) after distilled water injection. In diabetic rats, thickness was normal (P > 0.05) at most distances from the optic nerve but was subnormal (P < 0.05) in superior retina (0.5 mm from the optic nerve). Intraocular pressure was not different (P > 0.05) between groups. BRB was intact (P > 0.05) after saline and distilled water injection. Delta Po-2 was normal (P > 0.05) after saline injection and over inferior hemiretina of the diabetic group but was subnormal (P < 0.05) after distilled water injection and over superior hemiretina of diabetic rats. CONCLUSIONS. The lack of increased thickness in 3-month-old diabetic rats in vivo raises the possibility that intracellular swelling is unlikely to underlie subnormal Delta Po-2 in experimental diabetes. In diabetic rats, the spatial disconnect between subnormal Delta Po-2 pansuperiorly and retinal thinning only superiorly to the optic nerve suggests that neurovascular coupling is perturbed.