PMID- 30326207 OWN - NLM STAT- MEDLINE DCOM- 20190325 LR - 20190325 IS - 1096-0007 (Electronic) IS - 0014-4835 (Linking) VI - 178 DP - 2019 Jan TI - Pre-ischemic enriched environment increases retinal resilience to acute ischemic damage in adult rats. PG - 198-211 LID - S0014-4835(18)30383-X [pii] LID - 10.1016/j.exer.2018.10.007 [doi] AB - Retinal ischemia is a condition associated with several degenerative diseases leading to visual impairment and blindness worldwide. Currently, there is no highly effective therapy for ischemic retinopathies. This study was designed to determine possible benefits of pre-exposure to enriched environment against retinal damage induced by acute ischemia. For this purpose, adult male Wistar rats were randomly assigned to a pre-ischemic standard environment or a pre-ischemic enriched environment for 3 weeks, followed by unilateral ischemia induced by increasing intraocular pressure above 120 mm Hg for 40 min and reperfusion for 1 or 2 weeks in standard environment. Animals were subjected to electroretinography and histological analysis. Pre-ischemic enriched environment afforded significant functional protection in eyes exposed to ischemia/reperfusion injury. A marked reduction in retinal layer thickness, reduced synaptophysin-immunoreactivity and retinal ganglion cell (RGC) number, and increased microglia/macrophage reactivity were observed in ischemic retinas from animals submitted to pre-ischemic standard environment, which were prevented by pre-ischemic enriched environment. A deficit in anterograde transport from the retina to the superior colliculus and the lateral geniculate nucleus was observed in animals exposed to pre-ischemic standard environment, which was lower in animals previously exposed to enriched environment. The exposure to enriched environment before ischemia increased retinal brain derived neurotrophic factor (BDNF) protein levels in ischemic retinas and the administration of ANA-12 (a TrkB antagonist) abolished the protective effect of enriched environment on retinal function and retinal ganglion cell number. These results indicate that pre-ischemic enriched environment increases retinal resilience to acute ischemic damage, possibly through a BDNF/TrkB mediated pathway. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Gonzalez Fleitas, Maria F AU - Gonzalez Fleitas MF AD - Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, University of Buenos Aires/CEFyBO, CONICET, Buenos Aires, Argentina. FAU - Aranda, Marcos L AU - Aranda ML AD - Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, University of Buenos Aires/CEFyBO, CONICET, Buenos Aires, Argentina. FAU - Dieguez, Hernan H AU - Dieguez HH AD - Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, University of Buenos Aires/CEFyBO, CONICET, Buenos Aires, Argentina. FAU - Devouassoux, Julian D AU - Devouassoux JD AD - Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, University of Buenos Aires/CEFyBO, CONICET, Buenos Aires, Argentina. FAU - Chianelli, Monica S AU - Chianelli MS AD - Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, University of Buenos Aires/CEFyBO, CONICET, Buenos Aires, Argentina. FAU - Dorfman, Damian AU - Dorfman D AD - Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, University of Buenos Aires/CEFyBO, CONICET, Buenos Aires, Argentina. FAU - Rosenstein, Ruth E AU - Rosenstein RE AD - Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, University of Buenos Aires/CEFyBO, CONICET, Buenos Aires, Argentina. Electronic address: ruthr@fmed.uba.ar. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181013 PL - England TA - Exp Eye Res JT - Experimental eye research JID - 0370707 RN - 0 (ANA 12 compound) RN - 0 (Azepines) RN - 0 (Benzamides) RN - 0 (Biomarkers) RN - 0 (Eye Proteins) RN - 9012-63-9 (Cholera Toxin) SB - IM MH - *Adaptation, Physiological MH - Animal Husbandry/*methods MH - Animals MH - Azepines/pharmacology MH - Benzamides/pharmacology MH - Biomarkers/metabolism MH - Blotting, Western MH - Cholera Toxin/metabolism MH - Electroretinography MH - *Environment MH - Eye Proteins/metabolism MH - Male MH - Rats MH - Rats, Wistar MH - Reperfusion Injury/metabolism/physiopathology/*prevention & control MH - Retina/physiopathology MH - Retinal Diseases/metabolism/physiopathology/*prevention & control MH - Retinal Ganglion Cells/cytology MH - Retinal Vessels/physiopathology OTO - NOTNLM OT - Brain derived neurotrophic factor OT - Ischemia OT - Pre-ischemic enriched environment OT - Retina EDAT- 2018/10/17 06:00 MHDA- 2019/03/26 06:00 CRDT- 2018/10/17 06:00 PHST- 2018/05/17 00:00 [received] PHST- 2018/10/02 00:00 [revised] PHST- 2018/10/12 00:00 [accepted] PHST- 2018/10/17 06:00 [pubmed] PHST- 2019/03/26 06:00 [medline] PHST- 2018/10/17 06:00 [entrez] AID - S0014-4835(18)30383-X [pii] AID - 10.1016/j.exer.2018.10.007 [doi] PST - ppublish SO - Exp Eye Res. 2019 Jan;178:198-211. doi: 10.1016/j.exer.2018.10.007. Epub 2018 Oct 13.