Increased Indoleamine 2,3-Dioxygenase and Quinolinic Acid Expression in Microglia and Müller Cells of Diabetic Human and Rodent Retina

PURPOSE: We investigated the relationship between inflammation, neuronal loss, and expression of indoleamine 2, 3-dioxygenase (IDO) and quinolinic acid (QUIN) in the retina of subjects with type 1 diabetes (T1D) and type 2 diabetes (T2D) and in the retina of rats with T1D. METHODS: Retinas from T1D (n = 7), T2D (n = 13), and 20 age-matched nondiabetic human donors and from T1D (n = 3) and control rats (n = 3) were examined using immunohistochemistry for IDO, QUIN, cluster of differentiation 39 (CD39), ionized calcium-binding adaptor molecule (Iba-1, for macrophages and microglia), Vimentin (VIM; for Müller cells), neuronal nuclei (NeuN; for neurons), and UEA1 lectin (for blood vessels). RESULTS: Based on morphologic criteria, CD39(+)/ionized calcium binding adaptor molecule 1(Iba-1(+)) resident microglia and CD39(−)/Iba-1(+) bone marrow–derived macrophages were present at higher density in T1D (13% increase) and T2D (26% increase) human retinas when compared with controls. The density and brightness of IDO(+) microglia were increased in both T1D and T2D human retinas. The intensity of QUIN(+) expression on CD39(+) microglia and VIM(+) Müller cells was greatly increased in both human T1D and T2D retinas. T1D retinas showed a 63% loss of NeuN(+) neurons and T2D retinas lost approximately 43% when compared with nondiabetic human retinas. Few QUIN(+) microglia-like cells were seen in nondiabetic retinas, but the numbers increased 18-fold in T1D and 7-fold in T2D in the central retina. In T1D rat retinas, the density of IDO(+) microglia increased 2.8-fold and brightness increased 2.1-fold when compared with controls. CONCLUSIONS: Our findings suggest that IDO and QUIN expression in the retinas of diabetic rats and humans could contribute to the neuronal degeneration that is characteristic of diabetic retinopathy.