Establishment of a pigmented murine model abundant with characteristics of retinal vein occlusion

Miyagi, Sugao; Nishinaka, Anri; Yamamoto, Takumi; Otsu, Wataru; Nakamura, Shinsuke; Shimazawa, Masamitsu; Kitaoka, Takashi; Hara, Hideaki

doi:10.1016/j.exer.2021.108441

Cited by 7 publications

(12 citation statements)

References 28 publications

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“…We focused on cytokine protein levels at one day P-RVO and minimized laser-induced injury by decreasing laser exposure, power, and application. It is important to mention as well that RVO pathology is driven by retinal edema which we and others have reported previously not to be present in sham-lasered retinas [ 10 , 69 ].…”

Section: Discussionmentioning

confidence: 69%

“…Although it has been reported that sham-lasered exposed retinas expressed an increase in genes or mRNA levels associated with inflammation. The methodology of these studies used a much higher laser exposure time (2.5 s), laser applications (up to six) [ 68 ] or a much higher laser power (300 mW) [ 69 ]. Some of the cytokines that have been shown to be elevated in sham-lasered eyes are MCP-1, IL-6, and ICAM-1, but this increase has been reported to be present only at 0.5 days P-RVO and measured by mRNA levels [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

“…The methodology of these studies used a much higher laser exposure time (2.5 s), laser applications (up to six) [ 68 ] or a much higher laser power (300 mW) [ 69 ]. Some of the cytokines that have been shown to be elevated in sham-lasered eyes are MCP-1, IL-6, and ICAM-1, but this increase has been reported to be present only at 0.5 days P-RVO and measured by mRNA levels [ 69 ]. We focused on cytokine protein levels at one day P-RVO and minimized laser-induced injury by decreasing laser exposure, power, and application.…”

Section: Discussionmentioning

confidence: 99%

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Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline

et al. 2022

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Retinal neurovascular injuries are a leading cause of vision loss in young adults presenting unmet therapeutic needs. Neurovascular injuries damage homeostatic communication between endothelial, pericyte, glial, and neuronal cells through signaling pathways that remain to be established. To understand the mechanisms that contribute to neuronal death, we use a mouse model of retinal vein occlusion (RVO). Using this model, we previously discovered that after vascular damage, there was non-apoptotic activation of endothelial caspase-9 (EC Casp9); knock-out of EC Casp9 led to a decrease in retinal edema, capillary ischemia, and neuronal death. In this study, we aimed to explore the role of EC Casp9 in vision loss and inflammation. We found that EC Casp9 is implicated in contrast sensitivity decline, induction of inflammatory cytokines, and glial reactivity. One of the noted glial changes was increased levels of astroglial cl-caspase-6, which we found to be activated cell intrinsically by astroglial caspase-9 (Astro Casp9). Lastly, we discovered that Astro Casp9 contributes to capillary ischemia and contrast sensitivity decline after RVO (P-RVO). These findings reveal specific endothelial and astroglial non-apoptotic caspase-9 roles in inflammation and neurovascular injury respectively; and concomitant relevancy to contrast sensitivity decline.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline

et al. 2022

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“…Due to less opportunities to obtain retinal samples from RVO patients for high throughput sequencing, animal model mimicking the clinical characteristics of RVO seems more practical. For example, laser photocoagulation with eosin Y or rose bengal as photosensitizer is used to establish the animal model [ 7 , 27 ]. In our study, integrated bioinformatic analysis showed differential genes enriched in various inflammatory events in the gene expression profiling of the laser-induced mice RVO model (GSE101398).…”

Section: Discussionmentioning

confidence: 99%

Optical Coherence Tomography Angiography Characteristics Serve as Retinal Vein Occlusion Therapeutic Biomarkers for Dexamethasone Intravitreal Implant

2021

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Background. Retinal vein occlusion (RVO) is the second most common vision-threatening retinal vascular disease. Intravitreal dexamethasone implant has been applied to treat macular edema secondary to RVO (RVO-ME). However, the alteration of morphologic features detected with optical coherence tomography angiography (OCTA) has not been fully studied in RVO-ME patients before and after the treatment. Objective. This study is aimed at identifying potential therapeutic targets in RVO with integrative bioinformatic analysis and compares the OCTA characteristics alterations in patients with RVO-ME receiving injection of dexamethasone intravitreal implant. Methods. Bioinformatic analysis was analyzed in GSE101398 dataset from the Gene Expression Omnibus database. Multiple functional enrichment analyses were performed, and protein-protein interaction network was constructed to visualize the key node genes. Eleven eyes with RVO-ME were examined with OCTA before and after intravitreal dexamethasone implant. The OCTA parameters, including macular thickness, vessel density, foveal avascular zone parameters, the number of hyperreflective foci (HRF), area of cystoid edema, and subretinal fluid (SRF), were compared. The correlation was analyzed between best-corrected visual acuity (BCVA) and OCTA parameters. Results. A total of 79 differentially expressed genes were identified. Functional enrichment analyses revealed the enriched inflammatory events in RVO. In RVO-ME, Pearson correlation revealed that baseline BCVA was positively correlated with the area of SRF and central macular thickness, while no correlation was detected between baseline BCVA and HRF number or the area of cystoid edema. The visual acuity improved, and the central macular thickness was decreased after intravitreal dexamethasone implant injection. Besides, the number of HRF, the area of cystoid edema, and SRF were significantly alleviated after dexamethasone intravitreal injection. Conclusion. Retinal inflammation plays a crucial role in RVO pathogenesis. The imaging biomarkers of RVO including Müller glial intracellular edema, and retinal pigment epithelium dysfunction, could be assessed in OCTA and attenuated by intravitreal dexamethasone implant effectively.

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“…The occluded and damaged blood vessels as well as retinal ischemia can result in local hypoxia with the increased hypoxia inducible factor-1 alpha (HIF-1α), resulting in elevated secretion of vascular endothelial growth factor (VEGF), which could cause vascular hyperpermeability and neovascularization [3][4] . Anti-VEGF treatment has been shown to be beneficial to patients with RVO-ME and becomes the first-line therapy in the treatment of RVO-ME [5][6][7][8] . Besides VEGF, other factors including inflammatory cells and cytokines were also associated with the pathogenesis of RVO-ME.…”

Section: Introductionmentioning

confidence: 99%

Anti-VEGF reduces inflammatory features in macular edema secondary to retinal vein occlusion

Qin¹,

Zhang²,

Luo³

et al. 2022

Int J Ophthalmol

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AIM: To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with macular edema secondary to retinal vein occlusion (RVO-ME). METHODS: Twenty-eight eyes from twenty-eight treatment-naïve patients (14 males and 14 females) with RVO-ME were included in this retrospective study. The retinal vein occlusion (RVO) was comprised of both central retinal vein occlusion (CRVO, n=14) and branch retinal vein occlusion (BRVO, n=14). Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months, in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept. All eyes were imaged with optical coherence tomography angiography (OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection. The visual acuity (VA), central macular thickness (CMT), the number of hyperreflective foci (HRF) recognized as an inflammatory sign in OCT images, and non-perfusion area (NPA), were compared before and after anti-VEGF treatments. RESULTS: The mean interval between baseline and follow-up was 29.4±0.79 (range, 27-48)d. Compared with the baseline, the VA improved (logMAR 1.5±0.1 vs 0.8±0.1, P<0.05) and CMT decreased (460±34.0 μm vs 268.8±12.0 μm, P<0.05), significantly, after anti-VEGF treatment. The number of HRF was decreased significantly (76.5±4.8 vs 47.8±4.3, P<0.05) after anti-VEGF treatment. CONCLUSION: Anti-VEGF therapy is effective in treating RVO-ME. The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.

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Establishment of a pigmented murine model abundant with characteristics of retinal vein occlusion

Cited by 7 publications

References 28 publications

Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline

Neurovascular injury associated non-apoptotic endothelial caspase-9 and astroglial caspase-9 mediate inflammation and contrast sensitivity decline

Optical Coherence Tomography Angiography Characteristics Serve as Retinal Vein Occlusion Therapeutic Biomarkers for Dexamethasone Intravitreal Implant

Anti-VEGF reduces inflammatory features in macular edema secondary to retinal vein occlusion

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