Role of adrenergic receptors in vascular remodelling of the rat choroid

Abstract

1 Choroidal blood vessels, located between the sclera and retina, constitute the principle source of blood¯ow to ocular structures. The choroid is innervated by vasoconstrictor sympathetic and vasodilator parasympathetic nerves. 2 We have shown previously that sympathetic denervation for 6 weeks leads to signi®cant increases in choroidal thickness, percentage of choroid occupied by vascular lumina, and numbers of choroidal venules, large arterioles and outer retinal capillaries. Sympathetic dea erentation produces similar increases, indicating that loss of sympathetic nerve activity is responsible for increased vascularity after sympathectomy. Thus, sympathetic neurotransmission normally may be important in suppressing vascular proliferation in the adult rodent eye. 3 The aim of the present study was to determine whether sympathetic nerves act by way of adrenergic receptors to maintain normal choroidal vascular integrity. 4 The a-adrenoceptor antagonist, phentolamine (1 mg kg 71 day 71 ), the b-receptor antagonist, propranolol (1 mg kg 71 day 71 ), or saline vehicle was infused for 3 weeks using subcutaneously implanted osmotic minipumps. 5 In phentolamine treated rats, no signi®cant changes were noted relative to saline infused controls. However, propranolol treatment resulted in increases in choroidal thickness, vascular luminal area, and numbers of large choroidal venules and both small and large arterioles, approximating the remodelling seen after chronic sympathectomy. 6 We conclude that sympathetic nerves play a role in maintaining normal choroidal vascular architecture through actions mediated primarily by b-adrenoceptors.

Structural and functional MRI reveals multiple retinal layers

“…In contrast, the outer band as measured by MRI was significantly thicker than the histological determination of the choroidal vascular layer. We found only a single report of choroidal thickness (25-45 m) determined by histology (21). The discrepancy between the in vivo and histologic data could arise from collapse of choroidal vessels after removal of orbits from the systemic circulation, histological shrinkage, and͞or PVE because of limited MRI spatial resolution, underscoring the importance of measurements in vivo.…”

β3-Adrenergic Receptors Regulate Retinal Endothelial Cell Migration and Proliferation

“…Sympathectomy also produced significant increases in the number of choroidal venules and arterioles and the retinal capillaries in the outer nuclear layer (9). Additionally, we determined that the ␤-adrenergic receptor antagonist propranolol (which blocks ␤ 1 -and ␤ 2 -adrenergic receptors) produced changes in the choroid similar to those after a sympathectomy (10). Because the ␤ 3 -adrenergic receptor was thought to be found primarily in white and brown adipose tissues (11), we did not characterize the role of this receptor after sympathectomy.…”

Compound 49b: A Novel Beta-Adrenergic Receptor Agonist in the Treatment of Diabetic Retinopathy

“…In addition, previous work in our lab also showed that in vitro stimulation with propranolol, a beta-adrenergic receptor antagonist, caused similar changes as those seen after surgical sympathectomy while the alpha-adrenergic receptor antagonist, phentolamine, produced no changes (Steinle 2002). Because treatment with propranolol caused changes that were similar to sympathectomy, and stimulation with the alpha-adrenergic receptor antagonist showed no changes, we hypothesized that stimulation with a beta-adrenergic receptor agonist may prevent retinal changes induced by diabetes.…”

“…Current studies in our lab have shown that Müller cells possess B 1 (Walker & Steinle 2007) and B 2 -adrenergic receptors subtypes, while REC possess B 1 and B 3 -adrenergic receptor subtypes (Steinle & Smith 2002). Stimulation of the beta-adrenergic receptors on the above-mentioned cell types elicited beneficial effects in the retina, such as reductions in inflammatory and apoptotic markers.…”

“…In the eye, the sympathetic nerves have been shown to influence retinal function and diabetic retinopathy (Steinle & Smith 2002;Wiley et al 2005). In the past, it was believed that sympathetic nerves do not innervate the retina (Laties 1966); however, it was later shown that sympathetic nerves do innervate the retina (Furukawa 1987).…”