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Open AccessArticle

Novel Insights into Beta 2 Adrenergic Receptor Function in the rd10 Model of Retinitis Pigmentosa

Department of Biology, University of Pisa, 56127 Pisa, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(9), 2060; https://doi.org/10.3390/cells9092060
Received: 9 August 2020 / Revised: 31 August 2020 / Accepted: 8 September 2020 / Published: 9 September 2020
(This article belongs to the Special Issue Advances in Adrenergic Receptor Biology)
Background: In retinitis pigmentosa (RP), inherited rod death is followed by cone loss and blindness. Why cones die is still a matter of consideration. Here, we investigate the pathogenic role of the sympathetic transmission in the rd10 mouse model of RP. Methods: Retinal levels of beta adrenergic receptor (BAR) 2 and norepinephrine (NE) were measured. After administration of the BAR1/2 blocker propranolol or the hypoxia-inducible factor (HIF)-1 activator dimethyloxalylglycine (DMOG), retinal levels of HIF-1α, BAR2 or proteins involved in BAR2 desensitization were also measured. In DMOG treated mice, expression and localization of BAR2, inflammatory markers and cone arrestin were determined. Finally, rd10 mice were subjected to electroretinogram (ERG) analysis to assess rod and cone function. Results: In the rd10 retina, BAR2 overexpression and NE accumulation were found, with BAR2 immunoreactivity localized to Müller cells. BAR2 overexpression was likely due to desensitization defects. Upregulated levels of BAR2 were drastically reduced by propranolol that also restored desensitization defects. Due to the low level of HIF-1 consequent to the hyperoxic environment in the rd10 retina, we hypothesized a link between HIF-1 and BAR2. HIF-1α stabilization with DMOG resulted in i. increased HIF-1α accumulation, ii. decreased BAR2 levels, iii. restored desensitization processes, iv. reduced expression of inflammatory markers and v. increased cone survival without improved retinal function. Conclusions: Our results support a pathogenic role of the sympathetic system in RP that might help to understand why rd10 mice show a positive response to BAR blockers. View Full-Text
Keywords: retina degenerative disease; sympathetic transmission; desensitization; HIF-1α stabilization; inflammatory process; cone loss; retinal function retina degenerative disease; sympathetic transmission; desensitization; HIF-1α stabilization; inflammatory process; cone loss; retinal function
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MDPI and ACS Style

Cammalleri, M.; Dal Monte, M.; Amato, R.; Lapi, D.; Bagnoli, P. Novel Insights into Beta 2 Adrenergic Receptor Function in the rd10 Model of Retinitis Pigmentosa. Cells 2020, 9, 2060.

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