title: Effects of combined ketamine/xylazine anesthesia on light induced retinal degeneration in rats.
abstract: OBJECTIVE
  To explore the effect of ketamine-xylazine anesthesia on light-induced retinal degeneration in rats.
  
  
  METHODS
  Rats were anesthetized with ketamine and xylazine (100 and 5 mg, respectively) for 1 h, followed by a recovery phase of 2 h before exposure to 16,000 lux of environmental illumination for 2 h. Functional assessment by electroretinography (ERG) and morphological assessment by in vivo imaging (optical coherence tomography), histology (hematoxylin/eosin staining, TUNEL assay) and immunohistochemistry (GFAP and rhodopsin staining) were performed at baseline (ERG), 36 h, 7 d and 14 d post-treatment. Non-anesthetized animals treated with light damage served as controls.
  
  
  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 36 h (p<0.01) and significant reduction one week (p<0.01) after light damage. In contrast, ketamine-xylazine pre-treated animals showed no significant alteration of total retinal or ONL thickness at either time point (p>0.05), indicating a stabilizing and/or protective effect with regard to phototoxicity. Histology confirmed light-induced photoreceptor cell death and Müller cells gliosis in non-anesthetized rats, especially in the superior hemiretina, while ketamine-xylazine treated rats showed reduced photoreceptor cell death (TUNEL staining: p<0.001 after 7 d), thicker ONL and longer IS/OS. Fourteen days after light damage, a reduction of standard flash induced a-wave amplitudes and a-wave slopes (p = 0.01) and significant alterations in parameters of the scotopic sensitivity function (e.g. Vmax of the Naka Rushton fit p = 0.03) were observed in non-treated vs. ketamine-xylazine treated animals.
  
  
  CONCLUSIONS
  Our results suggest that pre-treatment with ketamine-xylazine anesthesia protects retinas against light damage, reducing photoreceptor cell death. These data support the notion that anesthesia with ketamine-xylazine provides neuroprotective effects in light-induced cell damage.
authors.affiliation: Division of Experimental Ophthalmology, Centre for Ophthalmology, Tuebingen, Germany.
authors.forename: Blanca
authors.initials: B
authors.lastname: Arango-Gonzalez
authors.forename: Andreas
authors.initials: A
authors.lastname: Schatz
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bolz
authors.forename: Javier
authors.initials: J
authors.lastname: Eslava-Schmalbach
authors.forename: Gabriel
authors.initials: G
authors.lastname: Willmann
authors.forename: Ahmad
authors.initials: A
authors.lastname: Zhour
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: M Dominik
authors.initials: MD
authors.lastname: Fischer
authors.forename: Florian
authors.initials: F
authors.lastname: Gekeler
mesh_terms: D000758:Anesthesia; D019162:Anesthetics, Combined / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D004596:Electroretinography; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007649:Ketamine / Q000494:pharmacology* / Q000627:therapeutic use; D008027:Light / Q000009:adverse effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D041623:Tomography, Optical Coherence; D014991:Xylazine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D019162:Anesthetics, Combined; D018696:Neuroprotective Agents; D014991:Xylazine; D007649:Ketamine