Imaging of Hypoxia in Retinal Vascular Disease

Abstract

Retinal tissue hypoxia is a key mediator in the pathogenesis of many leading causes of irreversible vision loss, including diabetic retinopathy. Retinal hypoxia in diabetic retinopathy has been shown to drive the production of pro-inflammatory cytokines and pro-angiogenic growth factors. Together, these factors contribute to disease progression by causing unregulated growth of new blood vessels, increased vascular permeability and cell death within the retina. Studies have shown that retinal hypoxia precedes many of the pathologic events that occur during the progression of diabetic retinopathy such as angiopathy, microaneurysms, and capillary dropout. Therefore, early detection of hypoxia in the retinas of diabetic patients could help clinicians identify problems in patients before irreversible damage has occurred. Currently, oxygen sensitive electrodes remain the gold standard for direct measurement of oxygen tension within the retinal tissue; however the procedure is highly invasive and is therefore limited in its applicability towards preclinical models. Less invasive techniques such as retinal oximetry, phosphorescence-lifetime imaging, and hypoxia-sensitive fluorescent probes have shown promising diagnostic value in facilitating detection of oxygen imbalance correlated with neurovascular dysfunction in DR patients. This review highlights the current progress and potential of these minimally invasive hypoxia-imaging techniques in diabetic retinopathy.

The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: a cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway

“…The HIFα-HIFβ complex can trigger transcription of genes with promoters presenting hypoxia response elements comprising erythropoietin and VEGF as during hypoxia; HIF-1 is expressed, binds to DNA, and tempts VEGF mRNA transcription [ 45 ]. Moreover, numerous research works supported the notion that hypoxia is a dynamic force in DR progression, rather than an outcome [ 46 , 47 ].…”

The role of the mTOR pathway in diabetic retinopathy

“…In addition, the RPE stabilizes the oBRB by providing vascular endothelial growth factor (VEGF) and other trophic factors to maintain the choroidal capillaries and their fenestrations. In a healthy individual, the most significant function of the choroidal circulation and the oBRB is to supply oxygen to photoreceptors, which are thought to consume more than 75% of retinal oxygen ( 12 , 13 ). Notably, the pathological hallmark of DR is reduced oxygen exchange and consumption, followed by a low arteriovenous difference and abnormal venous oxygen saturation ( 14 ).…”

Food Supplements in the Treatment of Ophthalmic Diseases: Preclinical and Clinical Studies

“…A direct consequence of inner blood-retinal barrier (iBRB) breakdown is the development of macular edema. Retinal neovascularization and macular edema are the result of increasing secretion of pro-inflammatory cytokines, and pro-angiogenic growth factors, among which predominates the vascular endothelial growth factor (VEGF) [312]. The retina is a highly metabolic active tissue, and high-glucose concentrations are particularly detrimental to its functioning.…”