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Agonism of β3-Adrenoceptors Inhibits Pathological Retinal Angiogenesis in the Model of Oxygen-Induced Retinopathy.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2024 Aug 01; Vol. 65 (10), pp. 34. - Publication Year :
- 2024
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Abstract
- Purpose: In response to hypoxia, sympathetic fibers to the retina activate β-adrenoceptors (β-ARs) that play an important role in the regulation of vascular and neuronal functions. We investigated the role of β3-AR using the mouse model of oxygen-induced retinopathy (OIR).<br />Methods: Mouse pups were exposed to 75% oxygen at postnatal day 7 (PD7) followed by a return to room air at PD12. The β3-AR preferential agonist BRL37344 was subcutaneously administered once daily at different times after the return to room air. At PD17, the OIR mice underwent flash and pattern electroretinogram. After sacrifice, retinal wholemounts were used for vessel staining or immunohistochemistry for astrocytes, Müller cells, or retinal ganglion cells (RGCs). In retinal homogenates, the levels of markers associated with neovascularization (NV), the blood-retinal barrier (BRB), or astrocytes were determined by western blot, and quantitative reverse-transcription polymerase chain reaction was used to assess β3-AR messenger. Administration of the β3-AR antagonist SR59230A was performed to verify BRL37344 selectivity.<br />Results: β3-AR expression is upregulated in response to hypoxia, but its increase is prevented by BRL37344, which counteracts NV by inhibiting the pro-angiogenic pathway, activating the anti-angiogenic pathway, recovering BRB-associated markers, triggering nitric oxide production, and favoring revascularization of the central retina through recovered density of astrocytes that ultimately counteracts NV in the midperiphery. Vasculature rescue prevents dysfunctional retinal activity and counteracts OIR-associated retinal ganglion cell loss.<br />Conclusions: β3-AR has emerged as a crucial intermediary in hypoxia-dependent NV, suggesting a role of β3-AR agonists in the treatment of proliferative retinopathies.
- Subjects :
- Animals
Mice
Animals, Newborn
Retinal Ganglion Cells pathology
Retinal Ganglion Cells drug effects
Retinal Ganglion Cells metabolism
Ethanolamines pharmacology
Retinal Vessels drug effects
Retinopathy of Prematurity metabolism
Retinopathy of Prematurity drug therapy
Astrocytes metabolism
Astrocytes drug effects
Immunohistochemistry
Angiogenesis
Retinal Neovascularization metabolism
Retinal Neovascularization prevention & control
Retinal Neovascularization pathology
Disease Models, Animal
Oxygen toxicity
Adrenergic beta-3 Receptor Agonists pharmacology
Mice, Inbred C57BL
Receptors, Adrenergic, beta-3 metabolism
Electroretinography
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 65
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 39186263
- Full Text :
- https://doi.org/10.1167/iovs.65.10.34