Lack of Galectin-3 attenuates neuroinflammation and protects the retina and optic nerve of diabetic mice

• Published in: Brain research Vol. 1700; pp. 126 - 137
• Main Authors: Mendonça, Henrique Rocha, Carvalho, Juliana Nicolau Aranha, Abreu, Carla Andreia, Mariano de Souza Aguiar dos Santos, Domethila, Carvalho, Julia Rios, Marques, Suelen Adriani, da Costa Calaza, Karin, Martinez, Ana Maria Blanco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2018
• Subjects: Diabetes; Galectin-3; Mice; Neurodegeneration; Optic nerve; Retina; Retina; Mice; Optic nerve; Galectin-3; Diabetes; Neurodegeneration
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2018.07.018

•Galectin-3 knockout mice present less retinal ganglion cell death than Wild-type mice after diabetes.•Galectin-3 knockout mice present less macrophage inflitration/proliferation within the optic nerve than Wild-type mice after diabetes.•Galectin-3 knockout mice macrophage/microglia within the optic nerve are less activated and less pro-inflammatory than Wild-type mice after diabetes.•Galectin-3 knockout mice astrocytes are less activated within the optic nerve than Wild-type mice after diabetes.•Galectin-3 knockout mice presents more myelinated fibers within the optic nerve than Wild-type mice after diabetes. Diabetic retinopathy is the leading cause of acquired blindness in working-age individuals. Recent work has revealed that neurodegeneration occurs earlier than vascular insult and that distal optic nerve damage precedes retinal degeneration and vascular insult. Since we have shown that optic nerve degeneration is reduced after optic nerve crush in Galectin-3 knockout (Gal-3 −/−) mice, we decided to investigate whether Gal-3 −/− could relieve inflammation and preserve both neurons and the structure of the retina and optic nerve following 8 weeks of diabetes. Diabetes was induced in 2-month-old male C57/bl6 WT or Gal-3 −/− mice by a single injection of streptozotocin (160 mg/kg). Histomorphometric retinal analyses showed no gross difference, except for a reduced number of retinal ganglion cells in WT diabetic mice, correlated to increased apoptosis. In the optic nerve, Gal-3 −/− mice showed reduced neuroinflammation, suggested by the smaller number of Iba1+ cells, particularly the amoeboid profiles in the distal end. Furthermore, iNOS staining was reduced in the optic nerves of Gal-3 −/− mice, as well as GFAP in the distal segment of the optic nerve. Finally, optic nerve histomorphometric analyses revealed that the number of myelinated fibers was higher in the Gal-3 −/− mice and myelin was more rectilinear compared to WT diabetic mice. Therefore, the present study provided evidence that Gal-3 is a central target that stimulates neuroinflammation and impairs neurological outcomes in visual complications of diabetes. Our findings provide support for the clinical use of Gal-3 inhibitors against diabetic visual complications in the near future.