Introduction: Retinal ischemia-reperfusion (IR) injury occurs in pathological situations that interrupt the blood flow to the retina, such as is the case during central retinal artery occlusion (CRAO). The animal models described in the literature are based on the pressure produced by the weight of a given quantity of saline elevated to a certain height; however, to establish these parameters it is necessary to perform mathematical calculations that cannot be easily redone in the case of punctual variations of intraocular pressure (IOP). The aim of this study was to present a new system that allows us to reproduce the conditions of retinal IR and thereby properly assess the level of injury in retinal histological samples. Methods: We developed a retinal IR model in WAG/RijHsd rats based on CRAO through increasing IOP. To develop this model, we produced ischemia for 1 h using a hydrostatic pressure system that maintained a constant high IOP and then allowed reperfusion for 1 h. The injury attributable to IR was assessed by histological examination of retinal samples, determining whether there was histological damage and/or dendritic swelling and counting the outer nuclear layer cells showing cytoplasmic swelling. Results: The increase in IOP to 150 mm Hg produced CRAO, in turn causing observable histological damage and dendritic swelling in all retinas subjected to IR. Counting the number of cells showing cytoplasmic swelling yielded a mean of 102.5 ± 35 cells/field. The contralateral retinas were healthy, showing no significant changes. Conclusion: The retinal IR model proposed is simple, reproducible, and allows variable durations of ischemia and reperfusion, and most importantly, it allows easy correction by adjusting the pressure of the sphygmomanometer, of any change in IOP to keep the ischemia stable, without having to recalculate the elevation height of the ischemia induction system. Moreover, the damage caused by IR can be effectively assessed by the type of histopathological assessment performed. For these reasons, it can be considered a reliable method for studying drugs that may prevent retinal IR injury.

1.
Bonne
C
,
Muller
A
,
Villain
M
.
Free radicals in retinal ischemia
.
Gen Pharmacol
.
1998
Mar
;
30
(
3
):
275
80
.
[PubMed]
0306-3623
2.
Berry
CE
,
Hare
JM
.
Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications
.
J Physiol
.
2004
Mar
;
555
(
Pt 3
):
589
606
.
[PubMed]
0022-3751
3.
Danton
GH
,
Dietrich
WD
.
Inflammatory mechanisms after ischemia and stroke
.
J Neuropathol Exp Neurol
.
2003
Feb
;
62
(
2
):
127
36
.
[PubMed]
0022-3069
4.
Cagin
YF
,
Atayan
Y
,
Sahin
N
,
Parlakpinar
H
,
Polat
A
,
Vardi
N
, et al.
Beneficial effects of dexpanthenol on mesenteric ischemia and reperfusion injury in experimental rat model
.
Free Radic Res
.
2016
;
50
(
3
):
354
65
.
[PubMed]
1071-5762
5.
Akhtar
MZ
,
Henderson
T
,
Sutherland
A
,
Vogel
T
,
Friend
PJ
.
Novel approaches to preventing ischemia-reperfusion injury during liver transplantation
.
Transplant Proc
.
2013
Jul-Aug
;
45
(
6
):
2083
92
.
[PubMed]
0041-1345
6.
Piper
HM
,
Abdallah
Y
,
Schäfer
C
.
The first minutes of reperfusion: a window of opportunity for cardioprotection
.
Cardiovasc Res
.
2004
Feb
;
61
(
3
):
365
71
.
[PubMed]
0008-6363
7.
Cearra
I.
Caracterización y tratamiento experimental del síndrome de isquemia - reperfusión en extremidades inferiores en la rata.
2016
.
8.
Campochiaro
PA
.
Molecular pathogenesis of retinal and choroidal vascular diseases
.
Prog Retin Eye Res
.
2015
Nov
;
49
:
67
81
.
[PubMed]
1350-9462
9.
Izumi
Y
,
Hammerman
SB
,
Benz
AM
,
Labruyere
J
,
Zorumski
CF
,
Olney
JW
.
Comparison of rat retinal fixation techniques: chemical fixation and microwave irradiation
.
Exp Eye Res
.
2000
Feb
;
70
(
2
):
191
8
.
[PubMed]
0014-4835
10.
Vestergaard
N
,
Cehofski
LJ
,
Honoré
B
,
Aasbjerg
K
,
Vorum
H
.
Animal Models Used to Simulate Retinal Artery Occlusion: A Comprehensive Review
.
Transl Vis Sci Technol
.
2019
Aug
;
8
(
4
):
23
.
[PubMed]
2164-2591
11.
Daugeliene
L
,
Niwa
M
,
Hara
A
,
Matsuno
H
,
Yamamoto
T
,
Kitazawa
Y
, et al.
Transient ischemic injury in the rat retina caused by thrombotic occlusion-thrombolytic reperfusion
.
Invest Ophthalmol Vis Sci
.
2000
Aug
;
41
(
9
):
2743
7
.
[PubMed]
0146-0404
12.
Shabanzadeh
AP
,
D’Onofrio
PM
,
Monnier
PP
,
Koeberle
PD
.
Neurosurgical Modeling of Retinal Ischemia-Reperfusion Injury
.
J Stroke Cerebrovasc Dis
.
2018
Apr
;
27
(
4
):
845
56
.
[PubMed]
1052-3057
13.
Sellés-Navarro
I
,
Villegas-Pérez
MP
,
Salvador-Silva
M
,
Ruiz-Gómez
JM
,
Vidal-Sanz
M
.
Retinal ganglion cell death after different transient periods of pressure-induced ischemia and survival intervals. A quantitative in vivo study
.
Invest Ophthalmol Vis Sci
.
1996
Sep
;
37
(
10
):
2002
14
.
[PubMed]
0146-0404
14.
Schmeer
C
,
Gámez
A
,
Tausch
S
,
Witte
OW
,
Isenmann
S
.
Statins modulate heat shock protein expression and enhance retinal ganglion cell survival after transient retinal ischemia/reperfusion in vivo
.
Invest Ophthalmol Vis Sci
.
2008
Nov
;
49
(
11
):
4971
81
.
[PubMed]
0146-0404
15.
Miltenyi Biotec. Dissection of retinas. Available from: https://www.miltenyibiotec.com/_Resources/Persistent/8cd0e563847e1afbc53413fcf7c2c100a128a2e7/SP-Retina-01.pdf [cited February 12, 2015].
16.
Senkichi
J
.
Embolic agents
.
Intervencionismo.
2016
;
16
(
1
):
16
26
.
17.
Niwa
M
,
Aoki
H
,
Hirata
A
,
Tomita
H
,
Green
PG
,
Hara
A
.
Retinal Cell Degeneration in Animal Models
.
Int J Mol Sci
.
2016
Jan
;
17
(
1
):
110
.
[PubMed]
1661-6596
18.
Hartsock
MJ
,
Cho
H
,
Wu
L
,
Chen
WJ
,
Gong
J
,
Duh
EJ
.
A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure
.
J Vis Exp
.
2016
Jul
;(
113
):
e54065
.
[PubMed]
1940-087X
19.
Nucci
C
,
Tartaglione
R
,
Cerulli
A
,
Mancino
R
,
Spanò
A
,
Cavaliere
F
, et al.
Retinal damage caused by high intraocular pressure-induced transient ischemia is prevented by coenzyme Q10 in rat
.
Int Rev Neurobiol
.
2007
;
82
:
397
406
.
[PubMed]
0074-7742
20.
Kim
BJ
,
Braun
TA
,
Wordinger
RJ
,
Clark
AF
.
Progressive morphological changes and impaired retinal function associated with temporal regulation of gene expression after retinal ischemia/reperfusion injury in mice
.
Mol Neurodegener
.
2013
Jun
;
8
(
1
):
21
.
[PubMed]
1750-1326
21.
Nakahara
T
,
Hoshino
M
,
Hoshino
S
,
Mori
A
,
Sakamoto
K
,
Ishii
K
.
Structural and functional changes in retinal vasculature induced by retinal ischemia-reperfusion in rats
.
Exp Eye Res
.
2015
Jun
;
135
:
134
45
.
[PubMed]
0014-4835
22.
Kin
H
,
Zhao
ZQ
,
Sun
HY
,
Wang
NP
,
Corvera
JS
,
Halkos
ME
, et al.
Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion
.
Cardiovasc Res
.
2004
Apr
;
62
(
1
):
74
85
.
[PubMed]
0008-6363
23.
Yazici
A
,
Aksit
H
,
Sari
ES
,
Yay
A
,
Erken
HA
,
Aksit
D
, et al.
Comparison of pre-treatment and post-treatment use of selenium in retinal ischemia reperfusion injury
.
Int J Ophthalmol
.
2015
Apr
;
8
(
2
):
263
8
.
[PubMed]
2222-3959
24.
Liu
XQ
,
Wu
BJ
,
Pan
WH
,
Zhang
XM
,
Liu
JH
,
Chen
MM
, et al.
Resveratrol mitigates rat retinal ischemic injury: the roles of matrix metalloproteinase-9, inducible nitric oxide, and heme oxygenase-1
.
J Ocul Pharmacol Ther
.
2013
Feb
;
29
(
1
):
33
40
.
[PubMed]
1080-7683
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