Role of the retinal vascular endothelial cell in ocular disease

Abstract

Retinal endothelial cells line the arborizing microvasculature that supplies and drains the neural retina. The anatomical and physiological characteristics of these endothelial cells are consistent with nutritional requirements and protection of a tissue critical to vision. On the one hand, the endothelium must ensure the supply of oxygen and other nutrients to the metabolically active retina, and allow access to circulating cells that maintain the vasculature or survey the retina for the presence of potential pathogens. On the other hand, the endothelium contributes to the blood-retinal barrier that protects the retina by excluding circulating molecular toxins, microorganisms, and pro-inflammatory leukocytes. Features required to fulfill these functions may also predispose to disease processes, such as retinal vascular leakage and neovascularization, and trafficking of microbes and inflammatory cells. Thus, the retinal endothelial cell is a key participant in retinal ischemic vasculopathies that include diabetic retinopathy and retinopathy of prematurity, and retinal inflammation or infection, as occurs in posterior uveitis. Using gene expression and proteomic profiling, it has been possible to explore the molecular phenotype of the human retinal endothelial cell and contribute to understanding of the pathogenesis of these diseases. In addition to providing support for the involvement of well-characterized endothelial molecules, profiling has the power to identify new players in retinal pathologies. Findings may have implications for the design of new biological therapies. Additional progress in this field is anticipated as other technologies, including epigenetic profiling methods, whole transcriptome shotgun sequencing, and metabolomics, are used to study the human retinal endothelial cell.

Molecular Signals Involved in Human B Cell Migration into the Retina:In VitroInvestigation of ICAM-1, VCAM-1, and CXCL13

“…Retinal endothelial cells used in the transendothelial migration studies were transduced with the mouse recombinant amphotropic retrovirus, LXSN16E6E7,(19) to generate sufficient cells for those studies. As we have previously reported,(18) the transduced cells retain their endothelial phenotype, including expression of endothelial markers and formation of capillary-like tubes on basement membrane substitute.…”

“…(18) In brief, the retinae were dissected from both eyes of cadaver donors, and digested with 0.2 mg/ml Dispase and 0.25–1 mg/ml type II collagenase (both from ThermoFisher Scientific-GIBCO, Grand Island, NY). After 7 to 10 days of culture in MCDB-131 medium (Sigma-Aldrich) supplemented with 2% fetal bovine serum (FBS) (HyClone-GE Healthcare Life Sciences, Logan, UT) and endothelial growth factors (EGM-2 SingleQuots supplement, omitting FBS, hydrocortisone and gentamicin; Clonetics-Lonza, Walkersville, MD) at 37 °C with 5% CO 2 , retinal endothelial cells were purified using magnetic Dynabeads (ThermoFisher Scientific-Invitrogen Dynal, Oslo, Norway) coated with mouse anti-human CD31 antibody, and grown in modified MCDB-131 medium with 10% FBS.…”

Interactions of TLR4 and PPARγ, Dependent on AMPK Signalling Pathway Contribute to Anti-Inflammatory Effects of Vaccariae Hypaphorine in Endothelial Cells

“…The endothelial dysfunction has been identified to be a high risk factor for cardiovascular diseases [4]. The inflammatory response produces numerous inflammatory mediators to accelerate the apoptosis of endothelial cells, and vascular permeability [5]. The endothelial cell activation in response to inflammatory stimuli is an initial event in diabetic retinopathy [6] and atherosclerosis [7].…”

Neisseria meningitidisEndogenous Endophthalmitis with Meningitis in an Immunocompetent Child

“…Retinal endothelial cells share many functional characteristics to the blood-brain barrier, including exclusion of leucocytes, microorganisms, and molecular toxins. 13 Taken together, these observations suggest the potential of using isolated anterior ciliary and ophthalmic arteries from eye bank tissue to elucidate bacterial virulence in meningitis and endophthalmitis. Ocular tissue may be more practically acquired than brain tissue and acquired from living donors with far greater potential for further investigation.…”

“…10 The reported child suffered both meningitis and endogenous endophthalmitis with anterior segment involvement; Neisseria meningitidis further invaded the endothelial interface of the child's blood-CSF barrier and bloodaqueous barrier (composed of iridovascular endothelia and ciliary epithelium). 13 Critical to the development of targeted future therapies is the molecular characterization of meningococcal penetration into sterile tissues such as the CNS and the eye.…”