The streptozotocin (STZ) diabetic rat develops retinal pathological alterations that resemble those observed in early human DR.
22 In early experimental diabetes (within 6 weeks), blood–retinal barrier breakdown,
23–26 leukostasis,
23,27,28 upregulation of endothelin-1,
29 abnormal retinal blood flow,
30–34 and reduced retinal arterial wall oxygen tension (PO
2)
35 have been reported in STZ rats, suggesting the possibility of alterations in DO
2_IR. However, significant reductions in tissue PO
2 may not occur even if oxygen delivery is reduced to some extent. In fact, indicators of hypoxia measured by pimonidazole
36 and hypoxia-inducible factor (HIF) levels
37 were not abnormal in excised retinal tissue of early STZ rats, though upregulation of vascular endothelial growth factor (VEGF)
24,38,39 has been reported. In addition to oxygen availability, retinal neural activity is also a determinant of the rate at which the retina consumes oxygen for energy generation. In early STZ rodents, neural changes including increased apoptosis of retinal ganglion cells,
40–43 thinning of the inner plexiform layer,
44 and reduction of amacrine cells
45 have been observed before the appearance of vascular cell changes,
22 suggesting that there may be alterations in MO
2_IR. However, to date, measurements of neither oxygen delivery nor oxygen metabolism in the inner retina in living STZ rats have been published. The purpose of this study was to quantitatively assess DO
2_IR and MO
2_IR in STZ rats with our previously established optical imaging method.
46,47