Animal Models of Retinal Vein Occlusion

Khayat, Meiaad; Lois, Noemi; Williams, Michael; Stitt, Alan W.

doi:10.1167/iovs.17-22788

Cited by 29 publications

(40 citation statements)

References 193 publications

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“…The study also reported that most animal models of RVO demonstrated spontaneous reperfusion and/or vascular remodeling, which seemed to occur more rapidly and effectively than in humans with RVO. 14 The period needed for developing collateral vessels to mature was much shorter in our model than that in human eyes, 27 possibly because the animals used for RVO models were young and healthy, whereas patients with RVO are often older and many have underlying systemic disorders, such as hypertension, dyslipidemia, dysfunctional thrombotic responses, or impaired glucose tolerance/diabetes, among others. 14 Because RVO in our animal model was artificially and acutely induced by laser photocoagulation, the process of the condition forming the RVO would be different than clinical cases.…”

Section: Discussionmentioning

confidence: 95%

“…The study that comprehensively reviewed animal RVO models has reported that all RVO models revealed early features classically observed in human, including cessation of blood flow and venous dilation, engorgement, and tortuosity distal to the occlusion site. 14 Moreover, the models generally demonstrated retinal hemorrhages and edema, which may make them suitable models to study the acute phase of RVO. 14 In our RVO model, those early characteristic features were found, indicating that our model can be considered suitable to study the acute phase of RVO.…”

Section: Discussionmentioning

confidence: 99%

“…The experimental animal models of RVO, wherein the functional and structural features resemble those of BRVO, can be used to study the pathogenesis of BRVO. 14 The dynamic changes around the induction of occlusion can be demonstrated using the experimental animal models of RVO induced by laser photocoagulation (PC) on a venule. 8,15,16 Recently, technological devices for measuring RBF have been developed so that it is possible to measure the absolute value of RBF by Doppler optical coherence tomography (DOCT) flowmeter 10,[17][18][19] and noninvasively evaluate the detailed microvascular formations by optical coherence tomography angiography (OCTA).…”

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confidence: 99%

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Longitudinal Changes in Retinal Blood Flow in a Feline Retinal Vein Occlusion Model as Measured by Doppler Optical Coherence Tomography and Optical Coherence Tomography Angiography

Wada

Song

Oomae

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We aimed to observe longitudinal changes in retinal blood flow (RBF) and structural transformations in capillaries using Doppler optical coherence tomography (DOCT) and optical coherence tomography angiography (OCTA) in a feline retinal blood occlusion (RVO) model. METHODS. RVO was induced by argon green laser photocoagulation (PC) in six eyes of six cats. RBF was measured at a first-order retinal artery and vein by a DOCT flowmeter, and structural changes in the capillaries around the occluded vessels (12 × 12 and 3 × 3 mm) were assessed by OCTA before (at baseline); immediately after PC; and on days 1, 4, 7, and 14 thereafter. Systemic and ocular parameters were monitored during the observation period. RESULTS. There were no significant differences in any systemic or ocular parameters before and after PC. Arterial RBF increased significantly on day 1 (160.6 ± 8.6% vs. baseline, P < 0.001) and decreased below baseline after day 1 through 14. Venous RBF decreased immediately after PC (17.4 ± 9.6% vs. baseline, P = 0.001) and then gradually increased afterwards, but did not return to baseline. OCTA showed dilatation of retinal venules immediately after PC to day 1. Collateral vessels began to form on day 4, had matured by day 7, and were pruned on day 14, which formed as mature as normal retinal venule diameters. CONCLUSIONS. With increasing arterial RBF within 1 day after inducing RVO, venules gradually expanded to form collateral vessels, suggesting that collateral vessels originate from existing capillary networks, not neovascularization.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Longitudinal Changes in Retinal Blood Flow in a Feline Retinal Vein Occlusion Model as Measured by Doppler Optical Coherence Tomography and Optical Coherence Tomography Angiography

Wada

Song

Oomae

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…these models have been used to improve the understanding of this condition and have shown their value on this regard (149) .…”

Section: A Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 99%

Ischemic retinal vein occlusion: characterizing the more severe spectrum of retinal vein occlusion

Khayat

Williams

Lois

2018

Survey of Ophthalmology

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Retinal vein occlusion (RVO)-including central RVO, branch RVO, and hemicentral and hemispheric RVO-is the second most common vascular cause of visual loss, surpassed only by diabetic retinopathy. The presence and extent of retinal ischemia in RVO is associated with a worse prognosis. On this basis, most previously conducted studies considered ischemic retinal vein occlusion (iRVO) and non-iRVO as separate entities based on set thresholds of existing retinal ischemia as determined by fundus fluorescein angiography. Other diagnostic technologies have been used specifically in the differentiation of ischemic central retinal vein occlusion and nonischemic central retinal vein occlusion. To date, there is no fully accepted definition for iRVO. Some clinicians and researchers may favor establishing a clear differentiation between these forms of RVO; others may prefer not to consider iRVO as a separate entity. Whatever the case, retinal ischemia in RVO confers a higher risk of visual loss and neovascular complications; thus, it should be determined as accurately as possible in patients with this disease and be considered in clinical and experimental studies. Most recently conducted clinical trials evaluating new treatments for macular edema secondary to RVO included none or only few patients with iRVO based on previous definitions (i.e., few patients with sizeable areas of retinal ischemia were recruited in these trials), and thus it is unclear whether the results observed in recruited patients could be extrapolated to those with retinal ischemia. There has been scant research aiming at developing and/or testing treatments for retinal ischemia, as well as to prevent new vessel formation as a result of RVO. We provide a detailed review of the knowledge gathered over the years on iRVO, from controversies on its definition and diagnosis to the understanding of its epidemiology, risk factors and pathogenesis, the structural and functional effects of this disease in the eye and its complications, natural history, and outcomes after treatment. In each section, the definition of iRVO used is given so, independently of whether iRVO is considered a separate clinical entity or a more severe end of the spectrum of RVO, the information will be useful to clinicians to determine patient's risk, guide therapeutic decisions, and counsel patients and for researchers to design future studies.

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“…Nevertheless, several animal models of vascular occlusion using laser photocoagulation, photodynamic coagulation, intravitreal injection of dermal fibroblasts, and diathermic cauterization have been proposed. 26 Among them, the photodynamic coagulation method 27 shows early features of the clinical disease, including retinal capillary dropout, hemorrhage, and edema. Herein, we developed an easy and reproducible model of CRVO in mice, which is particularly useful when analyzing genetically modified mice.…”

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confidence: 99%

Development of a Novel Model of Central Retinal Vascular Occlusion and the Therapeutic Potential of the Adrenomedullin–Receptor Activity–Modifying Protein 2 System

Hirabayashi

Tanaka

Imai

et al. 2019

The American Journal of Pathology

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Central retinal vein occlusion (CRVO) is an intractable disease that causes visual acuity loss with retinal ischemia, hemorrhage, and edema. In this study, we developed an experimental CRVO model in mice and evaluated the therapeutic potential of the pleiotropic peptide adrenomedullin (ADM) and its receptor activityemodifying protein 2 (RAMP2). The CRVO model, which had phenotypes resembling those seen in the clinic, was produced by combining i.p. injection of Rose bengal, a photoactivator dye enhancing thrombus formation, with laser photocoagulation. Retinal vascular area, analyzed using fluorescein angiography and fluorescein isothiocyanateeperfused retinal flat mounts, was decreased after induction of CRVO but gradually recovered from day 1 to 7. Measurements of retinal thickness using optical coherence tomography and histology revealed prominent edema early after CRVO, followed by gradual atrophy. Reperfusion after CRVO was diminished in Adm and Ramp2 knockout (KO) mice but was increased by exogenous ADM administration. CRVO also increased expression of a coagulation factor, oxidative stress markers, and a leukocyte adhesion molecule in both wild-type and Adm KO mice, and the effect was more pronounced in Adm KO mice. Using retinal capillary endothelial cells, ADM was found to directly suppress retinal endothelial injury. The retinoprotective effects of the Adm-Ramp2 system make it a novel therapeutic target for the treatment of CRVO.

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Animal Models of Retinal Vein Occlusion

Cited by 29 publications

References 193 publications

Longitudinal Changes in Retinal Blood Flow in a Feline Retinal Vein Occlusion Model as Measured by Doppler Optical Coherence Tomography and Optical Coherence Tomography Angiography

Longitudinal Changes in Retinal Blood Flow in a Feline Retinal Vein Occlusion Model as Measured by Doppler Optical Coherence Tomography and Optical Coherence Tomography Angiography

Ischemic retinal vein occlusion: characterizing the more severe spectrum of retinal vein occlusion

Development of a Novel Model of Central Retinal Vascular Occlusion and the Therapeutic Potential of the Adrenomedullin–Receptor Activity–Modifying Protein 2 System

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