Novel Mouse Model of Monocular Amaurosis Fugax

Novel Mouse Model of Monocular Amaurosis FugaxDominique Claude Lelong, MD; Ivan Bieche, PhD; Elodie Perez, MSc; Karine Bigot, PhD;

Julia Leemput, MSc; Ingrid Laurendeau, MSc; Michel Vidaud, PhD; Jean-Philippe Jais, MD, PhD;Maurice Menasche, PhD; Marc Abitbol, MD, PhD

Background and Purpose—Retinal ischemia is a major cause of visual impairment and is associated with a high risk ofsubsequent ischemic stroke. The retina and its projections are easily accessible for experimental procedures andfunctional evaluation. We created and characterized a mouse model of global and transient retinal ischemia and providea 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–polymerasechain reaction from the occurrence of unilateral 30-minute pterygopalatine artery occlusion until 4 weeks afterreperfusion. Electroretinograms evaluated functional sequelae 4 weeks after the ischemic episode and were correlatedwith histologic lesions.

Results—This model is the first to reproduce the features of transient monocular amaurosis fugax resulting fromophthalmic artery occlusion. The histologic structure was roughly conserved, but functional lesions affected ganglioncells, 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 characteristicupregulation of immediate-early genes and persistent functional deficits. The model should prove useful forinvestigating mechanisms of injury in genetically altered mice and for testing novel neuroprotective drugs. (Stroke.2007;38:000-000.)

Key Words: animal models � Gadd34 � heat-shock proteins � retinal ischemia

Retinal ischemia is a major cause of visual impairmentand blindness. It is involved in various clinical retinal

disorders, including ischemic optic neuropathies, obstructivearterial and venous retinopathies, carotid occlusive disorders,retinopathy of prematurity, chronic diabetic retinopathy, andglaucoma.1 Transient visual loss, or amaurosis fugax, is acondition commonly encountered in clinical practice, and itsfrequent causes include emboli from carotid atherothrombo-sis or, less frequently, from a cardioembolic source such asmitral valve prolapse. The risk of subsequent hemisphericinfarction is increased to �14% within 7 years of an episodeof amaurosis. Parallel changes occur in the retina and thebrain, even in the absence of traditional risk factors.2,3 Theretinotectal system and its projections (which originate fromthe prosencephalic vesicle) are an excellent model for study-ing neurodegenerative processes and neuroprotective strate-gies in the central nervous system, as they are easily acces-sible for experimental procedures and functional evaluation.

In this report, we characterize a new mouse model forglobal retinal ischemia that reproduces the symptoms of

human monocular amaurosis. In our model, we investigatedthe expression profiles of 6 genes known to be involved inimportant neuronal ischemic processes from acute ischemiato early and late reperfusion. Plasminogen activator inhibi-tor-1 (PAI-1) has been implicated in the regulation offibrinolysis4 and in that of N-methyl-D-aspartate receptor–mediated signaling.5 c-jun and c-fos are involved in transcrip-tional control,6 whereas cyclooxygenase (Cox)-2 is inducedduring inflammation.7 Gadd34 is a cell cycle protein upregu-lated in response to DNA damage, cell cycle arrest, andendoplasmic reticulum dysfunction.8 A molecular “chaper-one,” heat-shock protein (Hsp) 70, also functions as animportant cytoprotectant against oxidative stress and apopto-sis.9 We also measured the expression levels of 2 controlgenes, Thy-1 and Rho. These genes encode protein markersspecific for 2 types of retinal neurons: ganglion cells (Thy-1)and rod photoreceptors (Rho). Thy-1 mRNA levels provide asensitive and reliable index of retinal ganglion cell (RGC)injury,10 whereas Rho mRNA levels constitute an index of theglobal effect of ischemia on rod photoreceptors.11 We inves-

Received July 13, 2007; accepted August 7, 2007.From the Centre de Recherche Therapeutique en Ophtalmologie-CERTO (D.C.L., K.B., E.P., J.L., M.M., M.A.), Faculte de Medecine Paris Descartes;

Laboratoire de Genetique Moleculaire (I.B., I.L., M.V.), INSERM U745, Faculte des Sciences Pharmaceutiques et Biologiques; and Service debiostatistiques et d’informatique medicale (J.-P.J.), Faculte de Medecine Paris Descartes, Paris, France.

Correspondence to Marc Abitbol, CERTO, Faculte de Medecine Paris-Descartes, Site Necker, 156 rue de Vaugirard, 75015 Paris, France. [email protected]

© 2007 American Heart Association, Inc.

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tigated the correlation between gene expression profiles andresidual functional and histologic retinal lesions 4 weeks afteracute retinal ischemia.

Materials and MethodsAnimalsExperiments were performed in 8- to 10-week-old male C57BL/6Jmice (Charles River Laboratories, Lyon, France). The animals werehandled in accordance with European Union and French ethicalguidelines for the use of animals in neuroscience research.

SurgeryAnimals were anesthetized with 2% isoflurane (Aerrane, Baxter,Maurepas, France) and a mixture of 70% nitrous oxide and 30%oxygen delivered through a close-fitting facemask. Rectal tempera-tures were maintained at 37�0.5°C. The right common carotid arterywas exposed, and the external carotid artery was dissected, ligated,and sectioned to interrupt anastomoses between the ophthalmicartery and the external carotid artery vascular network. The internalcarotid artery and its first branch were then dissected, and a silksuture (10-0 Ethilon, Ethicon, Issy-les-Moulineaux, France) wastransiently tied around the pterygopalatine artery, which gives rise tothe ophthalmic artery. Ischemia was maintained for 15, 30, or 60minutes, after which the ligature was removed, reperfusion waschecked, and the neck incision was closed. Sham-operated animalsunderwent the same surgical procedure but did not undergo ligationof the pterygopalatine artery (supplemental Figure I, available onlineat http://stroke.ahajournals.org).12

Flat-Mounted RetinasIn group A (10 mice), the animals were killed after 30 minutes ofacute ischemia to assess the effects of global ischemia induced solelyby the surgical procedure and not followed by any reperfusion.Group B (18 mice with 3 animals for each ischemic duration in eachgroup) was used to test the reversal of ischemia at 2 different timesafter reperfusion (5 minutes and 1 hour) subsequent to the occurrenceof 3 distinct ischemic periods (15 minutes for group B15, 30 minutesfor group B30, and 60 minutes for group B60). All animals receivedintracardiac perfusion with fluorescein isothiocyanate (300 �L;Qiagen, Courtaboeuf, France) 2 minutes before being killed. Theperfusion pressure was controlled by spontaneous beating of theheart. All flat-mounted retinas were observed with a fluorescencemicroscope (DMRB, Leica Microsystemes, Rueil-Malmaison,France). For each animal, both the ischemic right eye and thenormally perfused contralateral left eye were removed and fixed byincubation overnight in 4% paraformaldehyde. The cornea and lenswere removed. The neural retinas were extracted, flattened by radialincisions, and mounted for further analysis of the macrovasculatureand microvasculature. The left eyes served as controls for the qualityof the entire procedure, including the evaluation of perfusionpressure.

Quantitative RT-PCRForty-two animals (group C) were killed at various times after 30minutes of retinal ischemia. This ischemic duration was chosen onthe basis of literature estimates, indicating that the threshold of themouse retinal ischemic tolerance ranges between 15 and 30 minutes,and on our preliminary studies demonstrating consistent electroreti-nogram (ERG) alterations after a 30-minute ischemia duration (datanot shown). Seven groups of samples were established, whichcorresponded to postischemic times of 0 hour, 1 hour, 4 hours, 24hours, 72 hours, 7 days, and 4 weeks. Six right neuroretinas (3 frommice subjected to ischemia and 3 from sham-operated mice) werecollected for RNA extraction for each time point.

The animals were decapitated after brief anesthesia under isoflu-rane (2%), nitrous oxide (30%), and oxygen (70%). Retinas wererapidly removed, frozen in LN2, and stored at �80°C until RNAextraction. Total RNA was extracted with TRIzol reagent (Invitro-gen, Cergy-Pontoise, France) according to the manufacturer’s in-

structions, and quantitative reverse transcription–polymerase chainreaction (qRT-PCR) was performed as previously described.13 Thenucleotide sequences of the primers used for qRT-PCR amplificationreactions are available on request.

ERG RecordingGroup D (25 mice) was used for functional evaluation of the retinaldamage caused by 30 minutes of ischemia, 4 weeks after the surgeryprocedure, by means of flash ERGs. ERGs were initially recorded 1week before ischemia to assess the comparability of the ischemic (13mice) and the sham-operated (12 mice) groups. ERG recordingswere then performed on the same animals 4 weeks after ischemia.Three animals (2 ischemic and 1 sham operated) were excluded fromthe ERG analysis due to hypothermia or recording artifacts. ERGrecordings were performed as described elsewhere.14

HistologyGroup D mice (13 animals subjected to 30 minutes of ischemia and12 sham-operated animals) were decapitated under anesthesia afterthe ERG recordings, as described in the previous paragraph. Righteyes were excised immediately after death, incubated in fixative (4%paraformaldehyde) overnight at 4°C, and embedded in paraffin.Sagittal sections (5 �m) were stained with hematoxylin and eosin.The thickness of each retinal layer (outer nuclear layer, outerplexiform layer, inner nuclear layer, inner plexiform layer, andretinal pigmented epithelium) was measured 150 �m from the centerof the optic nerve for the central retina and 300 �m from its extremeedge for the peripheral retina. Measurements were performed onboth sides of the optic nerve and on 3 adjacent sections to increasethe reliability of the collected data.

Statistical MethodsComparisons of groups for quantitative data were performed byrepeated-measures ANOVA with a mixed-model approach, whichtakes into account the animal as a random effect and flash intensitiesand experimental groups as fixed effects.15 All calculations wereperformed with SAS software, version 8.20 (SAS Institute, Cary,NC). The results are presented as mean�SEM. Values of P�0.05were considered statistically significant.

Results

The Model Induced Complete andReversible Retinal IschemiaOn flat-mounted right retinas, ophthalmic artery blood flowand blood resupply from the external carotid artery werecompletely interrupted in 10 consecutive animals in ourmodel (Figures 1A and 1C). No blood flow was observedfrom the central retinal artery and its branches vascularizingthe inner retina or from the choroidal vascularization ensuringthe supply of oxygen and nutrients to the retinal pigmentedepithelium and photoreceptor cells. Reperfusion was evalu-ated 5 minutes and 1 hour after the end of ischemia. It wasalmost immediate after 15 minutes of ischemia (group B15;Figures 2A and 2B) and was complete at 1 hour (Figures 2Cand 2D). Reperfusion was delayed after 30 minutes ofischemia (group B30; Figures 2E and 2F). One hour afterischemia, the B30 group displayed larger-caliber vessels thanthe B15 group, together with microaneurysms formation andintravascular deposits (Figure 2H). In the B60 group (whichunderwent 60 minutes of ischemia), reperfusion was juststarting at 1 hour (Figures 2K and 2L).

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qRT-PCR Displayed an Early and TransientIncrease in Immediate-Early Genes and aLate Decrease in Hsp70 mRNA LevelsAfter Transient IschemiaThe results are summarized in the Table. The PAI1 expres-sion pattern was biphasic, with 1 peak (2.5 times higher thannormal) at the end of ischemia and another (3.4-fold increase)24 hours after reperfusion. The c-jun, c-fos, and Cox-2mRNA levels showed 8-, 18-, and 5.4-fold increases, respec-tively, 1 hour after reperfusion; a decrease at 4 hours; and adecline to basal levels within 24 hours of reperfusion. Inaddition, Cox-2 levels were halved at 72 hours. A transientincrease in Gadd34 and Hsp70 mRNA levels (2.8- and3.4-fold, respectively) was observed 1 hour after reperfusion.The amount of Hsp70, Thy-1, and Rho mRNAs were halved4 weeks after ischemia.

Four Weeks After Surgery, 30 Minutes ofIschemia Resulted in a Significant Reductionof the Photopic and Scotopic b-Waves andof the Rod Photoreceptor WavesThe ERG reflects the sum of rod- and cone-mediated retinalresponses to light. The a-wave is derived from the photore-ceptors. The b-wave results from the interaction of bipolarcells and Muller cells.1 Ischemic and sham-operated micewere similar for all the parameters studied before the inter-vention. Under scotopic conditions, b-wave amplitude waslower in the ischemic group for all the flash intensities tested.This effect increased with flash intensities up to 10 cds/m2

(20%, P�0.005; Figure 3B). We also observed a significantdecrease in a-wave amplitude with flash intensity, of up to14% for a flash intensity of 10 cds/m2 (P�0.005; Figure 3A).No significant differences were observed between the 2groups for the a- and b- wave implicit times (data not shown).

Under photopic conditions, the response was cone mediated(Figure 4). The b-wave amplitude was significantly smaller(11%, P�0.05 for 10 cds/m2) in the ischemic group. Nosignificant differences between the 2 groups were observed inthe photopic a-wave amplitudes or in the photopic a- andb-wave implicit times (data not shown).

Preservation of Histologic StructureNo significant differences between the ischemic and sham-operated groups were observed in retinal layer thicknesses inthe central and peripheral retina (Figure 5 and supplementalFigure II, available online at http://stroke.ahajournals.org).

DiscussionWe have designed a purely vascular model of retinal ischemiathat reproduces transient human monocular amaurosis. Thismodel is noninvasive with respect to the eye and does notinduce blood-eye barrier effraction, mechanical lesions of theretina or optic nerve, contralateral eye lesions, or associatedbrain lesions in contrast to other currently available models.1

The model is reproducible and easily reversible and involvesthe vascular structure of the entire eye. Spontaneous reperfu-sion proceeds progressively from the central retina to theperiphery, and its duration increases with the duration ofischemia due to microvascular occlusion. Flat-mounted reti-nas show microthromboemboli (Figure 2), as observed inacute ischemic rat brains.16 The early and transient upregu-lation of PAI1 triggers vascular fibrin deposition and contrib-utes to the stabilization and growth of arterial thrombi byabolishing fibrinolysis.4 We observed a decrease in PAI1mRNA levels 1 hour after reperfusion. The plasminogenactivators tissue type (tPA) and urokinase type, which acti-vate the blood fibrinolytic system, are both present in theretina.5 Endogenous tPA potentiates the signaling mediated

Figure 1. Fluorescence microscopy offlat-mounted, fluorescein-perfused reti-nas (group A). Right ischemic retinaswere compared with left control retinasfrom the same animal. The surgical pro-cedure interrupted eye vascularization.

Lelong et al Murine Model of Amaurosis Fugax 3



by glutamatergic receptors, but PAI-1 protein blocks the tPAcatalytic site.5 Modification of the PAI1/tPA balance mayfavor reperfusion but may also increase tPA neurotoxiceffects.

Immediate-early genes (c-jun, c-fos, and Cox-2) werestrongly induced 1 hour after reperfusion. The proteins c-fosand c-jun are involved in coupling neuronal excitation totarget gene expression.6 The associated activation of c-junand c-fos, as shown by our results, is common during cerebralischemia17 and has been observed after intravitreal injectionof N-methyl-D-aspartate into the rat retina.18 Our model wascharacterized by a prominent and dramatic increase in c-fosmRNA levels. c-fos is a transcription factor that regulates thecellular mechanisms mediating neuronal excitability andsurvival.19 However, c-fos expression is also seen in neuronscommitted to apoptosis.20 The c-jun gene has been linked toneuronal apoptosis21and neuronal rescue.6

Ischemia also upregulates Cox-2 expression; we ob-served a peak at 1 hour and continued strong expression at4 hours. Cox-2 reaction products contribute to glutamateexcitotoxicity and to the deleterious effects of the inflam-matory reaction involving the ischemic brain,7 but Cox-2activity has also been implicated in the late phase ofischemic preconditioning.22 Cox-2 also plays a protectiverole in a model of ischemic retinopathy due to an anti-thrombotic mechanism.23

Gadd34 and Hsp70 are hallmarks of endoplasmic reticu-lum stress and unfolded protein response.8,24 In our retinalmodel, a peak in Gadd34 and Hsp70 mRNA levels was

Figure 2. Fluorescence microscopy of flat-mounted, fluorescein-perfused right retinas at 2 reperfusion times (5 minutes and 1 hour) afteracute ischemia for 15 minutes (group B15), 30 minutes (group B30), and 60 minutes (group B60). The surgical procedure was reversible.

Table. Sequential Expression Patterns of the Genes Studiedby qRT-PCR

Time After Retinal Ischemia

0 h 1 h 4 h 24 h 72 h 7 d 4 wk

PAI1 2.5 0.7 1.2 3.4 0.7 0.7 0.6

c-jun 1.1 8 2 1.1 0.9 0.7 0.9

c-fos 1.3 18 2.4 0.8 1.4 0.8 1

Cox-2 0.9 5.4 2.3 1.7 0.4 1.1 1.2

Gadd34 0.8 2.8 0.9 1.2 1 0.8 0.7

Hsp70 1.4 3.4 1.5 1.2 1.5 0.7 0.4

Thy-1 1 1.2 1 1.3 0.9 0.8 0.4

Rho 0.9 1 1 0.9 1.2 0.8 0.5

Because the precise amount of total RNA added to each reaction mix (based onoptical density) and its quality (ie, lack of extensive degradation) are both difficultto assess, we quantified transcripts of an endogenous RNA control gene (13). Eachsample was normalized on the basis of its RPLP0 (ribosomal protein, large, P0)content. For each gene and each time point, the result was expressed as a ratio ofthe median value of the 3 ischemic samples to the median value of the 3 shamsamples. Ratios �2 or �0.5 were considered significant.

Significant values are in bold.




observed 1 hour after ischemia. There are reports of Gadd34overproduction after brain ischemia,25 but there are no re-ported cases of Gadd34 being detected in the retina. Gadd34is unstable at both the mRNA and protein level.26 Changes inits expression are short lived in the absence of a positivelyperpetuating stress signal. As proximal stress sensors are nolonger activated, Gadd34 mRNA levels decrease in associa-tion with unfolded protein response activation. Gadd34 isassociated with cell rescue,25 the restoration of protein syn-thesis, and DNA repair. It is involved in ischemic precondi-tioning.27 However, by promoting the resumption of proteinsynthesis in a cell already burdened by unfolded proteins inthe endoplasmic reticulum, Gadd34 may also contribute tocell death.28 Gadd34 is a multifunctional protein and caninfluence programmed cell death in either a proapoptotic29 oran antiapoptotic8 way, depending on the cell type concernedand the nature and duration of the stress stimulus.

The induced expression of Hsp70 was significant buttransient. Little or no constitutive Hsp70 production has beenobserved in the brain, but Hsp70 is constitutively produced in

small amounts in the nuclei of photoreceptors and innersegments.30 These low levels of constitutive Hsp70 produc-tion in ocular structures may result from normal levels oflight and oxidative stress. The retina has the highest meta-bolic demand of any tissue in the body. Under normalphysiologic conditions and diurnal cycles, the adult retinaexists in a state of borderline hypoxia, making this tissueparticularly susceptible to even subtle decreases in perfu-sion.31 Nonetheless, the retina displays a remarkable naturalresistance to ischemic injury, much greater than that of thebrain.1 The induction of Hsp70 production in the brain andretina is associated with cellular resistance to various types ofdamage.9,32,33

Gadd34 and Hsp70 mRNA levels returned to basal values24 hours after ischemia, but a second larger peak wasobserved for PAI1 mRNA. In accordance with our results,Docagne and colleagues34 reported greater PAI1 mRNAlevels between 24 hours and 3 days after middle cerebralartery occlusion in mice. The 72-hour stage is characterizedby a decrease in Cox-2 gene expression. This minimum could

Figure 3. A, Summary of results(mean�SEM) showing the variation ina-wave amplitudes recorded underscotopic conditions with different flashintensities 4 weeks after 30 minutes ofischemia (n�11) or sham operation(n�11). A significant decrease (P�0.05*)in the a-wave amplitude was observedfor flash intensities of 1, 3, 10, and 25cds/m2 (respectively, P�0.039, P�0.013,P�0.005, P�0.007). B, Summary ofresults (mean�SEM) showing the varia-tion in b-wave amplitudes recordedunder scotopic conditions with differentflash intensities 4 weeks after 30 minutesof ischemia (n�11) or sham operation(n�11). A decrease in b-wave amplitudewas significantly different (P�0.05*) forflash intensities of 0.1, 0.3, 1, 3, 10, and25 cds/m2 (P�0.038, P�0.013, P�0.005,P�0.009, P�0.004, P�0.012,respectively).




be associated with the resolution of acute inflammatoryprocesses. No prominent upregulation or downregulation ofthe studied genes was seen 1 week after ischemia.

Low levels of Thy-1, Rho, and Hsp70 seem to be indicatorsof a dysfunctional retina and may precede histologic cellloss.10 We report evidences of retinal dysfunction in the formof qRT-PCR measurements and ERG recordings. A dimin-ished b-wave is a sensitive marker of ischemic injury, andsignificant decreases may be observed in tissues with near-normal histology.1 Structural changes are subtler, with only avery slight decrease in the total thickness of all cell layers inthe peripheral retina. ERG is therefore a more sensitiveindicator of ischemic retinal injury than histologic examina-tion. Furthermore, the use of techniques that measure thepanretinal effects of ischemia, such as ERG or qRT-PCR,have the advantage of not being subject to error resultingfrom nonuniform ischemic retinal changes, whereas histo-logic analysis may be inadvertently biased by patchy ische-mic injury.35 Previous studies that used retrogradely trans-ported tracers to identify the population of RGCs thatsurvived transient ischemia of the retina indicated that RGC

loss is an ongoing process that may last up to 3 months afterthe initial insult.1 Thy1 mRNA abundance and the number ofThy1-expressing cells decreased in advance of detectableRGC loss caused by 3 different modalities of damage. Thus,longer ischemic durations (at least 45 minutes) and/or longerdurations for observing animals after ischemia (3 months)may be necessary to detect significant histologic differencesin ischemic retinas whatever the methodology used is. Thisabsence of early histologic lesions combined with pureischemic alterations, which can be easily quantified bysensitive indicators such as ERG and even qRT-PCR latevariations, such as Thy-1, Rho, and Hsp70 mRNA modula-tions, suggest that there might be a window of opportunity fortherapeutic intervention in the novel model described in thisreport.

In conclusion, a murine model of transient retinal ischemiawas successfully developed that exhibited the characteristicupregulation of immediate-early genes and persistent func-tional deficits. The model should prove useful for investigat-ing mechanisms of injury in genetically altered mice and fortesting novel neuroprotective drugs.

Figure 4. A, Summary of results(mean�SEM) showing the variation ina-wave amplitudes recorded under pho-topic conditions with different flash inten-sities 4 weeks after 30 minutes of ische-mia (n�11) or sham operation (n�11). B,Summary of results (mean�SEM) show-ing the variation in b-wave amplitudesrecorded under photopic conditions withincreasing flash intensities 4 weeks after30 minutes of ischemia (n�11) or shamoperation (n�11). A decrease in b-waveamplitude was significantly different(P�0.05*) for flash intensities of 10 and25 cds/m2 (P�0.046, P�0.003,respectively).




AcknowledgmentsWe thank Dr N. Patey-Mariaud and Dr F. Jaubert (Serviced’anatomopathologie, Faculte de Medecine Necker-EnfantsMalades), Dr C. Marsac (CERTO) for helpful discussions, and E. LeGall for technical assistance.

Sources of FundingThis work was supported by RETINA-FRANCE and the Ministry forResearch of France.

DisclosuresNone.

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Figure 5. Measurements of retinal layersthicknesses 4 weeks after 30 minutes ofretinal ischemia or sham operation. A,Peripheral retina. A slightly but nonsig-nificantly decreased total retina thicknesswas observed between the ischemicgroup (n�13) and the sham group(n�12, mean�SEM). This possibledecreased retinal thickness suggests thepotential existence of minor histologiclesions in the peripheral regions of theischemic retina. B, Central retina. No dif-ference in retinal layer thicknesses(mean�SEM) was observed between theischemic (n�13) and sham (n�12)groups. TR indicates total retina; PE, pig-mentary epithelium; ONL, outer nuclearlayer; OPL, outer plexiform layer; INL,inner nuclear layer; and IPL, inner plexi-form layer.




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Figure I. Branches of the internal carotid artery in relation to theventral surface of the cranium in the rat (eye vascularization hasnot been determined accurately by other teams in the mouse).12




Figure II. Comparison of sham-operated and ischemic mouse retinas stained with hematoxylin and eosin 4 weeks after 30-minute is-chemia. Typical light photomicrographs of paraffin-embedded transverse sections of the peripheral retina (A) and central retina (C) fromsham-operated eyes and the peripheral retina (B) as well as the central retina (D) from ischemic eyes. GG indicates ganglion cell layer;IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; RPE, retinal pigmented epithe-lium; CB, ciliary body; and ON, optic nerve.




Laurendeau, Michel Vidaud, Jean-Philippe Jais, Maurice Menasche and Marc AbitbolDominique Claude Lelong, Ivan Bieche, Elodie Perez, Karine Bigot, Julia Leemput, Ingrid

Novel Mouse Model of Monocular Amaurosis Fugax

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Novel Mouse Model of Monocular Amaurosis Fugax