title: Who let the dogs out?: detrimental role of Galectin-3 in hypoperfusion-induced retinal degeneration.
abstract: BACKGROUND
  Retinal ischemia results in a progressive degeneration of neurons and a pathological activation of glial cells, resulting in vision loss. In the brain, progressive damage after ischemic insult has been correlated to neuroinflammatory processes involving microglia. Galectin-3 has been shown to mediate microglial responses to ischemic injury in the brain. Therefore, we wanted to explore the contribution of Galectin-3 (Gal-3) to hypoperfusion-induced retinal degeneration in mice.
  
  
  METHODS
  Gal-3 knockout (Gal-3 KO) and wildtype (WT) C57BL/6 mice were subjected to chronic cerebral hypoperfusion by bilateral narrowing of the common carotid arteries using metal coils resulting in a 30% reduction of blood flow. Sham operated mice served as controls. After 17 weeks, the mice were sacrificed and the eyes were analyzed for retinal architecture, neuronal cell survival, and glial reactivity using morphological staining and immunohistochemistry.
  
  
  RESULTS
  Hypoperfusion caused a strong increase in Gal-3 expression and microglial activation in WT mice, coupled with severe degenerative damage to all retinal neuronal subtypes, remodeling of the retinal lamination and Müller cell gliosis. In contrast, hypoperfused Gal-3 KO mice displayed a retained laminar architecture, a significant preservation of photoreceptors and ganglion cell neurons, and an attenuation of microglial and Müller cell activation.
  
  
  CONCLUSIONS
  Moderate cerebral blood flow reduction in the mouse results in severe retinal degenerative damage. In mice lacking Gal-3 expression, pathological changes are significantly attenuated. Gal-3 is thereby a potential target for treatment and prevention of hypoperfusion-induced retinal degeneration and a strong candidate for further research as a factor behind retinal degenerative disease.
authors.affiliation: Department of Ophthalmology, BMC, Lund University, Klinikgatan 26, Lund, S-22184, Sweden. oscar.manouchehrian_nilsson.027@student.lu.se.
authors.forename: Oscar
authors.initials: O
authors.lastname: Manouchehrian
authors.affiliation: Department of Ophthalmology, BMC, Lund University, Klinikgatan 26, Lund, S-22184, Sweden. karin.arner@med.lu.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Arnér
authors.affiliation: Experimental Neuroinflammation Laboratory, BMC, Lund University, Klinikgatan 26, Lund, S-22184, Sweden. tomas.deierborg@med.lu.se.
authors.forename: Tomas
authors.initials: T
authors.lastname: Deierborg
authors.affiliation: Department of Ophthalmology, BMC, Lund University, Klinikgatan 26, Lund, S-22184, Sweden. linnea.taylor@med.lu.se.
authors.forename: Linnéa
authors.initials: L
authors.lastname: Taylor
mesh_terms: D000818:Animals; D064026:Calbindins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000150:complications*; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051603:Recoverin / Q000378:metabolism; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012243:Rhodopsin / Q000378:metabolism; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D064026:Calbindins; D002135:Calcium-Binding Proteins; D037502:Galectin 3; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D051603:Recoverin; D012243:Rhodopsin; D011493:Protein Kinase C; D010751:Phosphopyruvate Hydratase; D005974:Glutamate-Ammonia Ligase