Novel mouse model of monocular amaurosis fugax.
OBJECTIVE
Retinal ischemia is a major cause of visual impairment and is associated with a high risk of subsequent ischemic stroke. The retina and its projections are easily accessible for experimental procedures and functional evaluation. We created and characterized a mouse model of global and transient retinal ischemia and provide a comprehensive chronologic profile of some genes that display altered expression during ischemia.


METHODS
Ischemia and reperfusion were assessed by observing flat-mounted retinas after systemic fluorescein injection. The temporal pattern of gene expression modulation was evaluated by quantitative reverse transcription-polymerase chain reaction from the occurrence of unilateral 30-minute pterygopalatine artery occlusion until 4 weeks after reperfusion. Electroretinograms evaluated functional sequelae 4 weeks after the ischemic episode and were correlated with histologic lesions.


RESULTS
This model is the first to reproduce the features of transient monocular amaurosis fugax resulting from ophthalmic artery occlusion. The histologic structure was roughly conserved, but functional lesions affected ganglion cells, inner nuclear layer cells, and photoreceptor cells. We observed an early and strong upregulation of c-fos, c-jun, Cox-2, Hsp70, and Gadd34 gene expression and a late decrease in Hsp70 transcript levels.


CONCLUSIONS
A murine model of transient retinal ischemia was successfully developed that exhibited the characteristic upregulation of immediate-early genes and persistent functional deficits. The model should prove useful for investigating mechanisms of injury in genetically altered mice and for testing novel neuroprotective drugs.
Lelong
Dominique Claude
DC
Centre de Recherche Thérapeutique en Ophtalmologie-CERTO, Faculté de Médecine Paris-Descartes, Site Necker, 156 rue de Vaugirard, 75015 Paris, France.
Bieche
Ivan
I
Perez
Elodie
E
Bigot
Karine
K
Leemput
Julia
J
Laurendeau
Ingrid
I
Vidaud
Michel
M
Jais
Jean-Philippe
JP
Menasche
Maurice
M
Abitbol
Marc
M
D020757:Amaurosis Fugax / Q000175:diagnosis* / Q000235:genetics*; D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology; D002343:Carotid Artery, Internal / Q000473:pathology; D018797:Cell Cycle Proteins / Q000502:physiology; D004195:Disease Models, Animal; D004596:Electroretinography / Q000379:methods; D005786:Gene Expression Regulation; D007511:Ischemia / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D054645:Protein Phosphatase 1; D051381:Rats; D015427:Reperfusion Injury; D012160:Retina / Q000473:pathology; D012164:Retinal Diseases / Q000175:diagnosis*; D013997:Time Factors
D000943:Antigens, Differentiation; D018797:Cell Cycle Proteins; D018696:Neuroprotective Agents; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1