Molecular Features of Classic Retinal Drugs, Retinal Therapeutic Targets and Emerging Treatments

Abstract

The management of exudative retinal diseases underwent a revolution due to the introduction of intravitreal treatments. There are two main classes of intravitreal drugs, namely anti-vascular endothelial growth factors (anti-VEGF) and corticosteroids molecules. The clinical course and the outcome of retinal diseases radically changed thanks to the efficacy of these molecules in determining the regression of the exudation and the restoration of the macular profile. In this review, we described the molecular features of classic retinal drugs, highlighting the main therapeutic targets, and we provided an overview of new emerging molecules. We performed a systematic review of the current literature available in the MEDLINE library, focusing on current intravitreal molecules and on new emerging therapies. The anti-VEGF molecules include Bevacizumab, Pegaptanib, Ranibizumab, Aflibercept, Conbercept, Brolucizumab, Abicipar-pegol and Faricimab. The corticosteroids approach is mainly based on the employment of triamcinolone acetonide, dexamethasone and fluocinolone acetonide molecules. Many clinical trials and real-life reports demonstrated their efficacy in exudative retinal diseases, highlighting differences in terms of molecular targeting and pharmacologic profiles. Furthermore, several new molecules are currently under investigation. Intravitreal drugs focus their activity on a wide range of therapeutic targets and are safe and efficacy in managing retinal diseases.

The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases

“…Neovascularization is the hallmark of DR. In the clinic, intravitreal injection of anti- VEGF agents such as bevacizumab, aflibercept, ranibizumab [ 210 ], which we described above in the AMD section, is the primary procedure to slow the progression of DR. To reduce the swelling of the retina, scatter laser surgery might be used to help block leaking blood vessels. In addition, laser surgery also helps shrink blood vessels and prevent them from proliferation.…”

Update of application of olfactory ensheathing cells and stem cells/exosomes in the treatment of retinal disorders

“…Laser photocoagulation can only be used for AMD where the location of the neurovascular injury is well defined and not in the fovea, and may result in impaired vision. Currently, anti-vascular endothelial growth factor (anti-VEGF) is mainly used for the treatment of wet AMD [ 7 , 8 ]. However, long-term use of anti-VEGF will not only reduce the efficacy, but may also lead to retinal hemorrhage, fibrosis and scarring, macular atrophy or retina map atrophy [ 9 , 10 ].…”

CXCL1-CXCR2 signalling mediates hypertensive retinopathy by inducing macrophage infiltration

“…For example, CCL5 is a potential systemic biomarker, and administration of a CCR2/CCR5 inhibitor (TAK-779) significantly reduces retinal vascular leakage in DR [ 27 , 28 ]. A CCR3 inhibitor (AKST4290) combined with intravitreal anti-VEGF injections has been used to treat exudative age-related macular degeneration (AMD) [ 29 ]. Several studies suggest that CXC chemokines, such as CXCL1, and their receptor CXCR2 are strongly associated with the migration and recruitment of monocytes/macrophages and neutrophils in different inflammatory diseases, including hypertension, cardiac remodelling, and atrial fibrillation [ 3 , 9 , 10 , 30 ].…”