Galectins in the Pathogenesis of Common Retinal Disease

Abstract

Diseases of the retina are major causes of visual impairment and blindness in developed countries and, due to an ageing population, their prevalence is continually rising. The lack of effective therapies and the limitations of those currently in use highlight the importance of continued research into the pathogenesis of these diseases. Vascular endothelial growth factor (VEGF) plays a major role in driving vascular dysfunction in retinal disease and has therefore become a key therapeutic target. Recent evidence also points to a potentially similarly important role of galectins, a family of β-galactoside-binding proteins. Indeed, they have been implicated in regulating fundamental processes, including vascular hyperpermeability, angiogenesis, neuroinflammation, and oxidative stress, all of which also play a prominent role in retinopathies. Here, we review direct evidence for pathological roles of galectins in retinal disease. In addition, we extrapolate potential roles of galectins in the retina from evidence in cancer, immune and neuro-biology. We conclude that there is value in increasing understanding of galectin function in retinal biology, in particular in the context of the retinal vasculature and microglia. With greater insight, recent clinical developments of galectin-targeting drugs could potentially also be of benefit to the clinical management of many blinding diseases.

Inhibition of Galectins and the P2X7 Purinergic Receptor as a Therapeutic Approach in the Neurovascular Inflammation of Diabetic Retinopathy

“…In particular, Gal-1 levels were increased in the vitreous fluid and epiretinal fibrovascular membrane of PDR patients compared with non-diabetic controls [179]. This was probably due to the higher Gal-1 secretion induced in retinal Müller cells and astrocytes by hyperglycemic conditions [136]. The upregulation of Gal-1 protein levels in vitreous samples rose substantially with DR progression, being present from the pre-ischemic inflammatory stage [186].…”

“…Gal-3 is localized at the ER-mitochondria interface and regulates the UPR [135]. It is involved in several processes underlying retinopathies, such as oxidative stress, proliferation, phagocytosis, apoptosis, oxidative stress, and angiogenesis [136]. Interestingly, Gal-3 may favor adaptive UPR following ERS by acting as both a pro-and anti-apoptotic regulator [135].…”

The Role of Galectin-3 in Retinal Degeneration and Other Ocular Diseases: A Potential Novel Biomarker and Therapeutic Target

“…Gal3 is mainly found in the cytoplasm and nucleus and can be secreted in non-classical ways [21]. Generally, the secreted Gal3 mediates cell migration, cell adhesion, and cell-to-cell interaction through Galectins exist both inside and outside cells, and it is worth noticing that they are synthesized in the cytoplasm [13]. When they are secreted outside, a non-classical pathway is involved, which is independent of the endoplasmic reticulum or Golgi apparatus [14].…”

“…Cytoplasmic Gal3 has considerate anti-apoptotic activity and regulates multiple signal transduction pathways, while nuclear Gal3 is associated with pre-mRNA splicing and gene expression. Its unique chimeric structure enables it to interact with excessive ligands, regulating various functions such as cell growth, adhesion, migration, invasion, angiogenesis, immune function, cell apoptosis, and endocytosis, emphasizing its importance in tumor progression [13].…”

“…This review aims to summarize the pathogenesis and therapeutic prospects of Gal3 in retinal degeneration and various ocular diseases in order to promote its application in clinical treatment and bring new insights to patients suffering from visual loss. Galectins exist both inside and outside cells, and it is worth noticing that they are synthesized in the cytoplasm [13]. When they are secreted outside, a non-classical pathway is involved, which is independent of the endoplasmic reticulum or Golgi apparatus [14].…”