Dexamethasone intravitreal implant downregulates PDGFR-α and upregulates caveolin-1 in experimental branch retinal vein occlusion

Cehofski, Lasse Jørgensen; Kruse, Andreas; Magnúsdóttir, Sigríður Olga; Alsing, Alexander Nørgård; Nielsen, Jonas Ellegaard; Kirkeby, Svend; Honoré, Bent; Vorum, Henrik

doi:10.1016/j.exer.2018.02.029

Cited by 16 publications

(42 citation statements)

References 46 publications

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“…Occlusion of four retinal veins was observed to be complicated by retinal ischemia. 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 ].…”

Section: Discussionmentioning

confidence: 99%

“…Reduction of disulfide bonds, alkylation with iodoacetamide, and acetone precipitation were performed as described in a previous work [ 13 ]. Digestion, TMT labeling, C18 spin column purification, and high pH reversed-phase peptide fractionation into 8 fractions were performed essentially as previously described [ 10 ].…”

Section: Methodsmentioning

confidence: 99%

“…The ion transfer tube temperature was 275 °C. Liquid chromatography and mass spectrometry using the TMT synchronous precursor selection MS3 mode were performed as described in detail in a recent study [ 13 ]. Briefly, peptides were separated on an Easy Spray TM analytical column at 40 °C (500 mm × 75 µm PepMap RSLC, C18, 2 µm, 100 Å, Thermo Scientific, Waltham, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed as previously described [ 13 ] using a primary monoclonal mouse anti-β-actin antibody 1:5000 (clone AC-15, Sigma-Aldrich, St. Louis, MO, USA), a primary polyclonal rabbit anti-IL-18 antibody 1:500 (MBS2026569, MyBioSource, San Diego, CA, USA), and a primary polyclonal rabbit anti-S100A12 antibody 1:100 (MBS2026249, MyBioSource, San Diego, CA, USA), diluted in 2.5% ( w / v ) skim milk blocking buffer. Log transformed densitometric data was used to perform a paired t -test.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Cehofski

Kruse

Kirkeby

et al. 2018

IJMS

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“…In the retina, Cav1 affects important visual processes such as phagolysosomal digestion of photoreceptor outer segments by the retinal pigment epithelium (RPE) (16), maintenance of retinal vascular blood-retinal-barrier integrity (17)(18)(19), and retinal neovascularization (20). We and others have also implicated Cav1 function specifically in retinal inflammation and immune response modulation (21)(22)(23). However, the specific role for Cav1 in retinal immunity is as perplexing as it has proven to be in extraocular tissue immune responses, and has only begun to be investigated (21).…”

mentioning

confidence: 99%

Neuroretinal-derived caveolin-1 promotes endotoxin-induced inflammation in the murine retina

Gurley

Gmyrek

McClellan

et al. 2020

Preprint

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Chronic ocular inflammation is associated with many retinal degenerative diseases that result in vision loss. The immune-privileged environment and complex organization of retinal tissue allow for the retina’s essential role in visual function processes, yet confound inquiries into cell-specific inflammatory effects that lead to retinal dysfunction and degeneration. Caveolin-1 (Cav1) is an integral membrane protein expressed in many retinal cell populations and has been implicated in retinal immune regulation. However, the direction (i.e., promotion or inhibition) in which Cav1 regulates inflammatory processes in the retina (as well as in other tissues) remains unclear. Previously, we showed that global-Cav1 depletion in the retina paradoxically resulted in reduced retinal inflammatory cytokine production with concurrent elevated retinal immune cell infiltration. We hypothesized that our previous results could be explained by cell-specific Cav1 functions in the retina. Here, we utilized our Chx10 (visual system homeobox 2)-Cre knockout model to deplete Cav1 specifically in the neural retinal (NR) compartment in order to clarify the role of neural retinal-specific Cav1 (NR-Cav1) in the retinal immune response to intravitreal LPS (lipopolysaccharide) challenge. Our data support that neural retinal-derived Cav1 promotes retinal tissue inflammation as Chx10-mediated Cav1 depletion was sufficient to suppress both retinal cytokine production and immune cell infiltration following inflammatory stimulation. Additionally, we identify Traf3 (tumor necrosis factor (TNF) receptor-associated factor 3) as a highly expressed potential immune modulator in retinal tissue that is upregulated with NR-Cav1 depletion. Furthermore, this study highlights the importance for understanding the role of Cav1 (and other proteins) in cell-specific contexts.

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Signalling pathways and cell death mechanisms in glaucoma: Insights into the molecular pathophysiology

Basavarajappa,

Galindo-Romero,

Gupta

et al. 2023

Molecular Aspects of Medicine

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Dexamethasone intravitreal implant downregulates PDGFR-α and upregulates caveolin-1 in experimental branch retinal vein occlusion

Cited by 16 publications

References 46 publications

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

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

Neuroretinal-derived caveolin-1 promotes endotoxin-induced inflammation in the murine retina

Signalling pathways and cell death mechanisms in glaucoma: Insights into the molecular pathophysiology

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