Harnessing retinal phagocytes to combat pathological neovascularization in ischemic retinopathies?

Abstract

Ischemic retinopathies (IR) are vision-threatening diseases that affect a substantial amount of people across all age groups worldwide. The current treatment options of photocoagulation and anti-VEGF therapy have side effects and are occasionally unable to prevent disease progression. It is therefore worthwhile to consider other molecular targets for the development of novel treatment strategies that could be safer and more efficient. During the manifestation of IR, the retina, normally an immune privileged tissue, encounters enhanced levels of cellular stress and inflammation that attract mononuclear phagocytes (MPs) from the blood stream and activate resident MPs (microglia). Activated MPs have a multitude of effects within the retinal tissue and have the potential to both counter and exacerbate the harmful tissue microenvironment. The present review discusses the current knowledge about the role of inflammation and activated retinal MPs in the major IRs: retinopathy of prematurity and diabetic retinopathy. We focus particularly on MPs and their secreted factors and cell–cell-based interactions between MPs and endothelial cells. We conclude that activated MPs play a major role in the manifestation and progression of IRs and could therefore become a promising new target for novel pharmacological intervention strategies in these diseases.

Senescent Cells: Dual Implications on the Retinal Vascular System

“…The spontaneous reparative vascular regression at the late stage of diseases usually attenuates the destructive costs and implications of the pathological neovessels [167]. This is supported by the fact that almost 90% of all affected ROP infants in the United States recover spontaneously without any therapeutic intervention [166,168,169]. Spontaneous regression of the pathological neovessels was also reported in DR individuals [170,171].…”

“…A growing body of evidence supports the significance of the inflammation and pro-inflammatory mediators in driving proliferative retinopathies and pathological neovascularization [177][178][179][180]. Stressed retinal cells boost local inflammation and recruit immune cells to the ischemic retina [168]. Stressed endothelial cells, for example, enhance leukocyte adhesion and transmigration in microvessels via upregulating adhesion molecules (ICAM-1, VCAM-1, etc.)…”

“…However, the underlying mechanisms of the vascular remodeling and regression in the retina are ill-defined. Long-term exposure to the hyperglycemia, hypoxia, and inflammatory stress induces damage to the neurovascular cells including endothelial cells and pericytes [168]. The leaky, misdirected, and abnormal formed vessels in the neovascularization phase is not capable to fully supply the high oxygen and nutrient demands of the retina, leads to the generation of a tissue microenvironment with profound oxidative, cellular, and inflammatory stress [168].…”

“…Long-term exposure to the hyperglycemia, hypoxia, and inflammatory stress induces damage to the neurovascular cells including endothelial cells and pericytes [168]. The leaky, misdirected, and abnormal formed vessels in the neovascularization phase is not capable to fully supply the high oxygen and nutrient demands of the retina, leads to the generation of a tissue microenvironment with profound oxidative, cellular, and inflammatory stress [168]. A growing body of evidence supports the significance of the inflammation and pro-inflammatory mediators in driving proliferative retinopathies and pathological neovascularization [177][178][179][180].…”

Potential biomarkers for retinopathy of prematurity identified by circular RNA profiling in peripheral blood mononuclear cells

“…indicated that peripheral macrophage depletion significantly inhibits pathological retinal neovascularization in OIR model in mice ( 25 ). Activation of mononuclear phagocytes may participate in the pathogenesis and development of ischemic retinopathies including ROP, which provide a new promising target in preventing these diseases ( 26 ). As the key drivers of immune responses, peripheral blood mononuclear cells (PBMCs) are comprised of variety types of immune cells, such as lymphocytes (T cells, B cells and natural killer cells), monocytes and dendritic cells ( 27 ).…”