Prolactin in Eyes of Patients with Retinopathy of Prematurity: Implications for Vascular Regression

Abstract

16K-PRL derived from PRL internalized from the circulation or synthesized intraocularly can stimulate apoptosis-induced vascular regression and contribute to the development and progression of ROP.

Vasoinhibins prevent retinal vasopermeability associated with diabetic retinopathy in rats via protein phosphatase 2A–dependent eNOS inactivation

“…Thus, vasoinhibins can be used to ameliorate multiple features of diabetic retinopathy. In line with this, PRL levels increase in the circulation and in ocular fluids of patients with advanced retinopathy of prematurity, and this increase was proposed to result in higher levels of intraocular vasoinhibins that can counteract the progression of the disease (20).…”

“…19). These peptides efficiently prevent VEGF-related angiogenesis and promote apoptosis-mediated vascular regression, as observed, for example, in retinopathy of prematurity (20). Vasoinhibins also inhibit bradykinin- and acetylcholine-induced relaxation of coronary vessels via Ca 2+ -dependent eNOS inactivation (21).…”

“…Current studies extend vasoinhibin function to inhibition of increases in vascular permeability that accompany almost all states of angiogenesis (42), including those in areas of diseased tissue in angiogenesis-related disorders such as diabetic retinopathy. The role of vasoinhibins as physio(patho)logical regulators of retinal vasculature is supported by their presence in the normal rat retina (22) and in the subretinal fluid and fibrovascular membranes of patients with retinopathy of prematurity (20). Blockage of vasoinhibins by the intravitreal injection of small, interfering RNA or neutralizing antibodies stimulates vessel growth and dilation in the retina (22) and inhibits apoptosis-mediated regression of intraocular blood vessels during development (20).…”

“…The role of vasoinhibins as physio(patho)logical regulators of retinal vasculature is supported by their presence in the normal rat retina (22) and in the subretinal fluid and fibrovascular membranes of patients with retinopathy of prematurity (20). Blockage of vasoinhibins by the intravitreal injection of small, interfering RNA or neutralizing antibodies stimulates vessel growth and dilation in the retina (22) and inhibits apoptosis-mediated regression of intraocular blood vessels during development (20). Notably, gene transfer of vasoinhibins via an adenoviral vector reduces angiogenesis in murine ischemia-induced retinopathy (43).…”

Matrix metalloproteases from chondrocytes generate an antiangiogenic 16 kDa prolactin

“…All protease inhibitors were from Sigma except the MMP inhibitor N-[2(R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide (referred to as GM-6001), which was from Calbiochem (San Diego, CA). Anti-rat PRL and anti-human PRL antisera were obtained and characterized as reported (Dueñas et al, 1999;Dueñas et al, 2004). Anti-rat PRL (INN-1; N-Term) and anti-human PRL (INN-368; C-Term) monoclonal antibodies that react with the N-terminal or the C-terminal end of PRL, respectively (Aranda et al, 2005), were provided by Peter Berger (Austrian Academy of Science, Innsbruck, Austria).…”