title: The β-adrenergic system as a possible new target for pharmacologic treatment of neovascular retinal diseases.
abstract: Retinal neovascular pathologies, such as diabetic retinopathy, retinopathy of prematurity (ROP) and age-related macular degeneration, may be treated with intravitreal injections of drugs targeting vascular endothelial growth factor (VEGF), the main inducer of neoangiogenesis; however further improvements and alternative strategies are needed. In the last few years, an intense research activity has focused on the β-adrenergic system. The results indicate that, in different experimental models, a decrease of the β-adrenergic function may result either in reduction or in exacerbation of the vascular changes, thus suggesting possible dual effects of β-adrenoreceptor (β-AR) modulation depending on the experimental setting. In in vivo models of proliferative retinopathies, most of the data point to a strong inhibitory role against vascular changes exerted by the blockade of specific β-ARs. In particular, the β2-AR seems to be the mostly involved in these responses, and the β1-/β2-AR blocker propranolol results highly effective in inhibiting both the increase of VEGF expression caused by a hypoxic insult and the consequent neovascular response. These observations have prompted clinical trials in preterm infants with ROP, where oral administrations of propranolol produced positive results in terms of efficacy, although safety problems were also reported. In addition, the possibility of using topical propranolol administrations in the form of eye drops opens new potential routes of drug administration in humans. A further point that should be considered is that there are data demonstrating significant antiapoptotic effects exerted by β-ARs, therefore if β-AR blockers were used to inhibit aberrant neovascularization, there may be a burden to pay in terms of impaired neuronal viability.
authors.affiliation: Department of Biology, University of Pisa, via San Zeno, 31, 56127 Pisa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casini
authors.affiliation: Department of Biology, University of Pisa, via San Zeno, 31, 56127 Pisa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Dal Monte
authors.affiliation: Department of Biology, University of Pisa, via San Zeno, 31, 56127 Pisa, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Fornaciari
authors.affiliation: Neonatal Intensive Care Unit, Medical Surgical Feto-Neonatal Department, "A. Meyer" University Children's Hospital, Viale G. Pieraccini, 24, 50139 Florence, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Filippi
authors.affiliation: Department of Biology, University of Pisa, via San Zeno, 31, 56127 Pisa, Italy. Electronic address: paola.bagnoli@unipi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Bagnoli
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D051379:Mice; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012160:Retina / Q000502:physiology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000503:physiopathology; D015861:Retinal Neovascularization / Q000188:drug therapy
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta
keywords: Angiogenesis; Neuroprotection; Oxygen-induced retinopathy model; Preterm infants; β-AR blockade; β1/β2-AR knock-out mice