A Review: Proteomics in Retinal Artery Occlusion, Retinal Vein Occlusion, Diabetic Retinopathy and Acquired Macular Disorders

Cehofski, Lasse Jørgensen; Honoré, Bent; Vorum, Henrik

doi:10.3390/ijms18050907

Cited by 49 publications

(63 citation statements)

References 103 publications

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“…Although anti-VEGF therapeutic strategies have been employed thus far, the involvement of additional cellular factors 30 and symptoms beyond angiogenesis 2,27,29 show that neovascular retinal diseases are multifactorial conditions for which currently available treatments may be inadequate to address. Additionally, these treatments require frequent administration on a long-term basis, 3 from which other issues may arise, including safety concerns. 31 For example, anti-VEGF therapy has been shown to accelerate fibrotic responses in PDR patients as a result of changes in the ratio of VEGF to connective tissue growth factor (CTGF) levels.…”

Section: Discussionmentioning

confidence: 99%

“…A ngiogenic retinal pathologies, which include diabetic retinopathy (DR), retinal vein occlusion (RVO), and retinopathy of prematurity (RoP), are among the leading causes of vision loss in developed nations. 1 With DR currently affecting approximately 100 million patients worldwide and diabetes mellitus projected to have a global incidence rate of 592 million by 2035, 2 it can be seen that these conditions, of which RVO is the second most common neovascular retinal disease, 3 constitute a growing health concern. The most salient characteristic shared among these disorders is retinal neovasculariza-tion, a process for which vascular endothelial growth factor (VEGF) serves as a main driver.…”

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confidence: 99%

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Inhibition of mTOR via an AAV-Delivered shRNA Tested in a Rat OIR Model as a Potential Antiangiogenic Gene Therapy

Lee

Chang²,

Kim

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Citation: Lee SHS, Chang H, Kim JH, et al. Inhibition of mTOR via an AAV-Delivered shRNA tested in a rat OIR model as a potential antiangiogenic gene therapy. Invest Ophthalmol Vis Sci. 2020;61(2):45. https://doi.org/10.1167/iovs.61.2.45 PURPOSE.Recent studies have shown that inhibitors of the mechanistic target of rapamycin (mTOR) play important roles in proliferating endothelial cells within the retinal vasculature. Here we explore the effects of inhibiting mTOR as a potential gene therapeutic against pathological retinal angiogenesis in a rat model of oxygen-induced retinopathy (OIR). METHODS.Sprague-Dawley pups were used to generate the OIR model, with a recombinant adeno-associated virus expressing an shRNA (rAAV2-shmTOR-GFP) being administered via intravitreal injection on returning the rats to normoxia, with appropriate controls. Immunohistochemistry and TUNEL assays, as well as fluorescein angiography, were performed on transverse retinal sections and flat mounts, respectively, to determine the in vivo effects of mTOR inhibition. RESULTS.Compared with normal control rats, as well as OIR model animals that were either untreated (20.95 ± 6.85), mock-treated (14.50 ± 2.47), or injected with a control short hairpin RNA (shRNA)-containing virus vector (16.64 ± 4.92), rAAV2-shmTOR-GFP (4.28 ± 2.86, P = 0.00103) treatment resulted in dramatically reduced neovascularization as a percentage of total retinal area. These results mirrored quantifications of retinal avascular area and vessel tortuosity, with rAAV2-shmTOR-GFP exhibiting significantly greater therapeutic efficacy than the other treatments. The virus vector was additionally shown to reduce inflammatory cell infiltration into retinal tissue and possess antiapoptotic properties, both these processes having been implicated in the pathophysiology of angiogenic retinal disorders. CONCLUSIONS.Taken together, these results demonstrate the strong promise of rAAV2-shmTOR-GFP as an effective and convenient gene therapy for the treatment of neovascular retinal diseases.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Inhibition of mTOR via an AAV-Delivered shRNA Tested in a Rat OIR Model as a Potential Antiangiogenic Gene Therapy

Lee

Chang²,

Kim

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…We previously conducted studies in which only one retinal vein was occluded [ 10 , 11 , 12 , 13 ]. Occlusion of a single retinal vein in healthy pigs does not result in retinal ischemia and retinal thickening [ 11 , 14 ]. However, the present study revealed that retinal thickening occurs when four retinal veins are occluded.…”

Section: Discussionmentioning

confidence: 99%

IL-18 and S100A12 Are Upregulated in Experimental Central Retinal Vein Occlusion

Cehofski

Kruse

Kirkeby

et al. 2018

IJMS

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Retinal vein occlusion (RVO) is a common retinal vascular disease. RVO may be complicated by pronounced ischemia that often leads to severe loss of visual function. The present work aimed at studying the retinal proteome of RVO complicated by ischemia. In six Danish Landrace pigs RVO was induced with argon laser in the right eye of each animal. As four retinal veins were occluded, the RVO best corresponded to a central retinal vein occlusion (CRVO). Left control eyes received a similar laser treatment without inducing occlusion. RVO and retinal ischemia were verified by angiography. The retinas were collected 15 days after RVO for proteomic analysis. RVO resulted in a downregulation of proteins involved in visual perception, including rhodopsin, transducin alpha chain, and peripherin-2. RVO also caused a downregulation of proteins involved in neurotransmitter transport, including glutamate decarboxylase 1 (GAD1), glutamate decarboxylase 2 (GAD2), and complexins 2–4. RVO lead to increased contents of proteins involved in inflammation, including interleukin-18 (IL-18), S100A12, and annexin A1 (ANXA1). Immunohistochemistry revealed a general retinal upregulation of IL-18 and ANXA1 while S100A12 was highly abundant in retinal ganglion cells in RVO. IL-18 and S100A12 are likely to be driving forces in the inflammatory response of RVO complicated by ischemia. Our findings also suggest that RVO results in compromised neurotransmission and a downregulation of proteins involved in visual perception.

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“…However, many areas of proteome changes in RVO remain unstudied. Future studies may address long-lasting retinal changes following intervention with anti-VEGF agents, such as dexamethasone intravitreal implants [15]. These two clusters, assigned to Quadrant III, represents research hotspots which are marginal and immature, and future research on these topics is suggested.…”

Section: Discussionmentioning

confidence: 99%

Theme trends in research related to retinal vein occlusion: a quantitative and co-word analysis

Liu

Chen

Zhao

2019

Preprint

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Background. This study focused on plotting knowledge structure and exploring research hotspots of retinal vein occlusion (RVO). Methods. In this study, research articles, with subject of RVO, were acquired from PubMed. Bibliographic Item Co-Occurrence Matrix Builder (BICOMB) was used for MeSH terms acquisition, evaluation and high-frequency MeSH term determination. Biclustering analysis and knowledge structure were conducted based on the MeSH term-source article matrix. RVO theme trends were illustrated with social network analysis (SNA), along with strategic diagrams. Results. A total of 3179 articles on RVO were retrieved, and the annual research output increased with time. USA ranked first with the most publications, with Retina as the most prolific journal in RVO research. MeSH terms were characterized into five different genres. As shown by the strategic diagram, the complications of RVO, the etiology of macular edema, as well as the therapeutic use of anti-VEGF, steroids and anti-inflammatory agents were well developed (Quadrant I). In contrast, epidemiology, metabolism and genetics related research on RVO were relatively immature (Quadrant III). Research on surgical treatments of vitrectomy, diagnostic methods and pathology of RVO were centralized but undeveloped (Quadrant IV). The SNA results was exhibited by the centrality chart, on which the node position was represented by the centrality values. Conclusions. By providing a bibliometric research, the overall RVO research trends could be revealed based on the five categories identified by this study. The mathematical bibliometric study could shed light on new perspectives for researchers. Background Retinal vein occlusion (RVO) ranks the second most common cause of retinal vascular disease [1]. Central (CRVO), hemiretinal (HRVO) and branch (BRVO) vein occlusion are the three major categories of RVO based on the occlusion site. Patient symptoms may generally include, depending on the classification of RVO, blurry or missing vision, floating dots or lines, and defective visual field. The main complications of CRVO include the macular edema formation, neovascularization, neovascular glaucoma, and vitreous hemorrhage, while complications of BRVO depend more on the vessel occluded [2]. Academic journals have published a vast amount of papers in RVO related research over recent decades. In order to reduce the effort and time required for a traditional systematic literature

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A Review: Proteomics in Retinal Artery Occlusion, Retinal Vein Occlusion, Diabetic Retinopathy and Acquired Macular Disorders

Cited by 49 publications

References 103 publications

Inhibition of mTOR via an AAV-Delivered shRNA Tested in a Rat OIR Model as a Potential Antiangiogenic Gene Therapy

Inhibition of mTOR via an AAV-Delivered shRNA Tested in a Rat OIR Model as a Potential Antiangiogenic Gene Therapy

IL-18 and S100A12 Are Upregulated in Experimental Central Retinal Vein Occlusion

Theme trends in research related to retinal vein occlusion: a quantitative and co-word analysis

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