Evaluation of the Effect of a Novel <i>β3</i>-Adrenergic Agonist on Choroidal Vascularity

Topçuoğlu, Murat; Aslan, Fatih

doi:10.1167/iovs.62.9.17

Cited by 4 publications

(1 citation statement)

References 42 publications

(59 reference statements)

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“…In human choroidal endothelial cells, β3-AR activation contributes to cell invasion, proliferation and elongation thus suggesting β3-AR involvement in ocular diseases characterized by choroidal neovascularization [74]. These findings have been confirmed by recent data of Topcuoglu and Aslan [75] who have demonstrated that in patients with an overactive bladder, routinary treatment with mirabegron significantly increases choroidal vascular parameters suggesting that β3-ARs may have a role in eye diseases associated with choroidal vascularization.…”

Section: Discussionsupporting

confidence: 53%

HIF-1-Dependent Induction of β3 Adrenoceptor: Evidence from the Mouse Retina

Amato

Pisani

Laudadio

et al. 2022

Cells

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A major player in the homeostatic response to hypoxia is the hypoxia-inducible factor (HIF)-1 that transactivates a number of genes involved in neovessel proliferation in response to low oxygen tension. In the retina, hypoxia overstimulates β-adrenoceptors (β-ARs) which play a key role in the formation of pathogenic blood vessels. Among β-ARs, β3-AR expression is increased in proliferating vessels in concomitance with increased levels of HIF-1α and vascular endothelial growth factor (VEGF). Whether, similarly to VEGF, hypoxia-induced β3-AR upregulation is driven by HIF-1 is still unknown. We used the mouse model of oxygen-induced retinopathy (OIR), an acknowledged model of retinal angiogenesis, to verify the hypothesis of β3-AR transcriptional regulation by HIF-1. Investigation of β3-AR regulation over OIR progression revealed that the expression profile of β3-AR depends on oxygen tension, similar to VEGF. The additional evidence that HIF-1α stabilization decouples β3-AR expression from oxygen levels further indicates that HIF-1 regulates the expression of the β3-AR gene in the retina. Bioinformatics predicted the presence of six HIF-1 binding sites (HBS #1-6) upstream and inside the mouse β3-AR gene. Among these, HBS #1 has been identified as the most suitable HBS for HIF-1 binding. Chromatin immunoprecipitation-qPCR demonstrated an effective binding of HIF-1 to HBS #1 indicating the existence of a physical interaction between HIF-1 and the β3-AR gene. The additional finding that β3-AR gene expression is concomitantly activated indicates the possibility that HIF-1 transactivates the β3-AR gene. Our results are indicative of β3-AR involvement in HIF-1-mediated response to hypoxia.

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Section: Discussionsupporting

confidence: 53%

HIF-1-Dependent Induction of β3 Adrenoceptor: Evidence from the Mouse Retina

Amato

Pisani

Laudadio

et al. 2022

Cells

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The β3 adrenoceptor in proliferative retinopathies: “Cinderella” steps out of its family shadow

Cammalleri

Amato

Monte

et al. 2023

Pharmacological Research

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Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

et al. 2022

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Retinopathy of prematurity (ROP) is an evolutive and potentially blinding eye disease that affects preterm newborns. Unfortunately, until now no conservative therapy of active ROP with proven efficacy is available. Although ROP is a multifactorial disease, premature exposition to oxygen concentrations higher than those intrauterine, represents the initial pathogenetic trigger. The increase of oxygenation in a retina still incompletely vascularized promotes the downregulation of proangiogenic factors and finally the interruption of vascularization (ischemic phase). However, the increasing metabolic requirement of the ischemic retina induces, over the following weeks, a progressive hypoxia that specularly increases the levels of proangiogenic factors finally leading to proliferative retinopathy (proliferative phase). Considering non-modifiable the coupling between oxygen levels and vascularization, so far, neonatologists and ophthalmologists have “played defense”, meticulously searching the minimum necessary concentration of oxygen for individual newborns, refining their diagnostic ability, adopting a careful monitoring policy, ready to decisively intervene only in a very advanced stage of disease progression. However, recent advances have demonstrated the possibility to pharmacologically modulate the relationship between oxygen and vascularization, opening thus the perspective for new therapeutic or preventive opportunities. The perspective of a shift from a defensive towards an attack strategy is now at hand.

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Evaluation of the Effect of a Novel β3-Adrenergic Agonist on Choroidal Vascularity

Cited by 4 publications

References 42 publications

HIF-1-Dependent Induction of β3 Adrenoceptor: Evidence from the Mouse Retina

HIF-1-Dependent Induction of β3 Adrenoceptor: Evidence from the Mouse Retina

The β3 adrenoceptor in proliferative retinopathies: “Cinderella” steps out of its family shadow

Decoupling Oxygen Tension From Retinal Vascularization as a New Perspective for Management of Retinopathy of Prematurity. New Opportunities From β-adrenoceptors

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