The role of the retinal pigment epithelium and Müller cells secretome in neovascular retinal pathologies

Araújo, Rute S.; Santos, Daniela F.; Silva, Gabriela A.

doi:10.1016/j.biochi.2018.06.019

Cited by 23 publications

(12 citation statements)

References 57 publications

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“…While there is a paucity of data regarding physiologic ocular HTRA-1 expression, published work suggests a predominance of expression in the RPE, consistent with our finding that the increase in HtrA-1 expression under OIR conditions was most apparent in the RPE (Chan et al, 2007). Further, HTRA-1 is a secreted protein and there is precedent for the RPE secretome in ROP and other retinal neovascular disease mechanisms as reviewed by Araújo et al (2018). Therefore, the correlation between elevated systemic HTRA-1 and ROP in preterm infants may confer relevance to local disease mechanisms.…”

Section: Discussionmentioning

confidence: 99%

The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization

Owen

Shirer

Collazo

et al. 2020

Front. Mol. Neurosci.

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Retinopathy of prematurity (ROP) is a blinding aberrancy of retinal vascular maturation in preterm infants. Despite delayed onset after preterm birth, representing a window for therapeutic intervention, we cannot prevent or cure ROP blindness. A natural form of ROP protection exists in the setting of early-onset maternal preeclampsia, though is not well characterized. As ischemia is a central feature in both ROP and preeclampsia, we hypothesized that angiogenesis mediators may underlie this protection. To test our hypothesis we analyzed peripheral blood expression of candidate proteins with suggested roles in preeclamptic and ROP pathophysiology and with a proposed angiogenesis function (HTRA-1, IGF-1, TGFβ-1, and VEGF-A). Analysis in a discovery cohort of 40 maternal-infant pairs found that elevated HTRA-1 (high-temperature requirement-A serine peptidase-1) was significantly associated with increased risk of ROP and the absence of preeclampsia, thus fitting a model of preeclampsia-mediated ROP protection. We validated these findings and further demonstrated a dose-response between systemic infant HTRA-1 expression and risk for ROP development in a larger and more diverse validation cohort consisting of preterm infants recruited from two institutions. Functional analysis in the oxygen-induced retinopathy (OIR) murine model of ROP supported our systemic human findings at the local tissue level, demonstrating that HtrA-1 expression is elevated in both the neurosensory retina and retinal pigment epithelium by RT-PCR in the ROP disease state. Finally, transgenic mice over-expressing HtrA-1 demonstrate greater ROP disease severity in this model. Thus, HTRA-1 may underlie ROP protection in preeclampsia and represent an avenue for disease prevention , which does not currently exist.

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Section: Discussionmentioning

confidence: 99%

The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization

Owen

Shirer

Collazo

et al. 2020

Front. Mol. Neurosci.

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“…BRB breakdown is a complex process that is regulated by multiple factors and involves different mechanisms, and when it occurs at inner and/or outer BRB, excess fluid can accumulate, and this can result in macular oedema. Regarding fluid exit, the drainage system depends on a complex system of transport of ion/water channels located in the polarized retinal pigment epithelium (RPE) cells and the retinal Müller glial cells [ 2 , 25 ].…”

Section: Pathophysiology Of Diabetic Macular Oedemamentioning

confidence: 99%

Rho-Kinase Inhibitors for the Treatment of Refractory Diabetic Macular Oedema

Mateos-Olivares

García-Onrubia

Valentín-Bravo

et al. 2021

Cells

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Diabetic macular oedema (DMO) is one of the leading causes of vision loss associated with diabetic retinopathy (DR). New insights in managing this condition have changed the paradigm in its treatment, with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) having become the standard therapy for DMO worldwide. However, there is no single standard therapy for all patients DMO refractory to anti-VEGF treatment; thus, further investigation is still needed. The key obstacles in developing suitable therapeutics for refractory DMO lie in its complex pathophysiology; therefore, there is an opportunity for further improvements in the progress and applications of new drugs. Previous studies have indicated that Rho-associated kinase (Rho-kinase/ROCK) is an essential molecule in the pathogenesis of DMO. This is why the Rho/ROCK signalling pathway has been proposed as a possible target for new treatments. The present review focuses on the recent progress on the possible role of ROCK and its therapeutic potential in DMO. A systematic literature search was performed, covering the years 1991 to 2021, using the following keywords: “rho-Associated Kinas-es”, “Diabetic Retinopathy”, “Macular Edema”, “Ripasudil”, “Fasudil” and “Netarsudil”. Better insight into the pathological role of Rho-kinase/ROCK may lead to the development of new strategies for refractory DMO treatment and prevention.

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“…It was reported that glia cells in brain, retina and peripheral nervous system secrete various growth factors, extracellular matrix proteins, Adams (A disintegrin and metalloprotease), Adamts (A disintegrin and metalloproteinase with thrombospondin motif) neurite growth regulating proteins and proteins involved in synaptogenesis, in addition to proteins involved in regulating vasculogenesis and blood retina or blood brain barrier (Araujo et al, 2018;Jha et al, 2018;Ruzafa et al, 2018;Schira et al, 2019;Vecino et al, 2016;von Toerne et al, 2014). The protein profile of the porcine retinal Muller glia secretome were reported earlier (Ruzafa et al, 2018;von Toerne et al, 2014), and were mainly focused on identifying growth factors that support the survival of photoreceptors and RGC.…”

Section: Identification Of Neuroprotective and Neurite Growth Promoting Factors In The Secretome Of Muller Glia After Induction Or Inhibimentioning

confidence: 99%

“…Muller cells are the predominant glial cell type in the retina, and they structurally and metabolically support retinal neurons (Araujo, Santos, & Silva, 2018;Vecino, Rodriguez, Ruzafa, Pereiro, & Sharma, 2016). Co-cultures of primary rat and porcine Muller glia improve the survival of RGCs and protect them from harmful effects of glutamate, high glucose concentration and NMDA treatment (Furuya, Pan, & Kashiwagi, 2012;Kashiwagi et al, 2004;Matteucci et al, 2014;Skytt et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The effect of extrinsic Wnt/β‐catenin signaling in Muller glia on retinal ganglion cell neurite growth

Musada

Dvoriantchikova

Myer

et al. 2020

Developmental Neurobiology

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The role of the retinal pigment epithelium and Müller cells secretome in neovascular retinal pathologies

Cited by 23 publications

References 57 publications

The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization

The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization

Rho-Kinase Inhibitors for the Treatment of Refractory Diabetic Macular Oedema

The effect of extrinsic Wnt/β‐catenin signaling in Muller glia on retinal ganglion cell neurite growth

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