No abstract

Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, –C, -D, and placental growth factor [PlGF]) constitute the VEGF family. VEGF-A binds VEGF receptors 1 and 2 (VEGFR1/2), whereas VEGF-B and PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown the importance and involvement of VEGFR1 and its family of ligands in angiogenesis, vascular permeability, and microinflammatory cascades within the retina. Expression of VEGFR1 depends on the microenvironment, is differentially regulated under hypoxic and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), Müller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less clear. VEGFR1 activation can affect vascular permeability and induce macrophage and microglia production of proinflammatory and proangiogenic mediators. However the ability of the VEGFR1 ligands (VEGF-A, PlGF, and VEGF-B) to compete against each other for receptor binding and to heterodimerize complicates our understanding of the relative contribution of VEGFR1 signaling alone toward the pathologic processes seen in diabetic retinopathy, retinal vascular occlusions, retinopathy of prematurity, and age-related macular degeneration. Clinically, anti-VEGF drugs have proven transformational in these pathologies and their impact on modulation of VEGFR1 signaling is still an opportunity-rich field for further research.

The SERC provided a diverse group of approximately 150 scientists and physicians representing industry and academia from 14 countries with a unique opportunity to explore the latest approaches to drug and gene delivery to the posterior segment of the eye. Unlike the 2009 SERC meeting, which focused on novel drug delivery platforms while elucidating the anatomic barriers to reach the posterior segment, 1 the most recent meeting explored strategies for bypassing ocular barriers using novel materials, nanoparticulate delivery systems, and gene therapy. It brought together experts in both ophthalmology and tangentially related areas to discuss the application and inherent technical challenges for translating experimental results from the laboratory bench to dependable medical therapies at the bedside and, where possible, it exemplified findings in ocular models with methods and results gleaned from disciplines outside of ophthalmology. The present review of the SERC provides investigators with tools to navigate these nascent approaches by exploring strategies from key laboratory investigations, drug development specialists, and clinical trials.The 2-day conference comprised the following six sessions: (1) barriers to drug delivery and transporter-guided drug design; (2) drug/gene delivery systems and cell therapies for the eye; (3) pharmacokinetics (PK), pharmacodynamics, and alternative routes of drug delivery; (4) nanotechnology for diagnosis and treatment of posterior eye disease; (5) translation of gene delivery for posterior eye disease; and (6) clinical trials.Rather than being a deliberate summary of each presentation, this review describes the common themes expressed during the six sessions.

In this rabbit study, the Retisert provides relatively constant levels of FA in the posterior pole, which is consistent with previous reports of its clinical utility.

No abstract