Effects of Combined KetamineXylazine Anesthesia on Light Induced Retinal Degeneration in Rats 英文参考文献.docVIP

EffectsofCombinedKetamine/XylazineAnesthesiaon LightInducedRetinalDegenerationinRats BlancaArango-Gonzalez1.,AndreasSchatz1.,SylviaBolz1,JavierEslava-Schmalbach2, GabrielWillmann1,AhmadZhour1,EberhartZrenner1,M.DominikFischer1*,FlorianGekeler1 1Division of Experimental Ophthalmology, Centre for Ophthalmology, Tuebingen, Germany, 2Clinical Research Institute, National University of Colombia, Bogota, Colombia Abstract Objectives:Toexploretheeffectofketamine-xylazineanesthesiaonlight-inducedretinaldegenerationinrats. Methods:Ratswereanesthetizedwithketamineandxylazine(100and5mg,respectively)for1h,followedbyarecovery phase of 2h before exposure to 16,000 lux of environmental illumination for 2h. Functional assessment by electroretinography (ERG) and morphological assessment by in vivo imaging (optical coherence tomography), histology (hematoxylin/eosinstaining, TUNELassay)andimmunohistochemistry (GFAPandrhodopsinstaining)wereperformed at baseline(ERG),36h,7dand14dpost-treatment.Non-anesthetizedanimalstreatedwithlightdamageservedascontrols. Results: Ketamine-xylazine pre-treatment preserved retinal function and protected against light-induced retinal degeneration. In vivo retinal imaging demonstrated a significant increase of outer nuclear layer (ONL) thickness in the non-anesthetized group at 36h (p,0.01) and significant reduction one week (p,0.01) after light damage. In contrast, ketamine-xylazinepre-treatedanimalsshowednosignificantalterationoftotalretinalorONLthicknessateithertimepoint (p.0.05),indicatingastabilizingand/orprotectiveeffectwithregardtophototoxicity.Histologyconfirmedlight-induced photoreceptor cell death and Mu¨ller cells gliosis in non-anesthetized rats, especially in the superior hemiretina, while ketamine-xylazinetreatedratsshowedreducedphotoreceptorcelldeath(TUNELstaining:p,0.001after7d),thickerONL andlongerIS/OS.Fourteendaysafterlightdamage,areductionofstandardflashinduceda-waveamplitudesanda-wave slopes(p=0.01)andsignificantalterations