New Insights Into Immunological Therapy for Retinal Disorders

Abstract

In the twentieth century, a conspicuous lack of effective treatment strategies existed for managing several retinal disorders, including age-related macular degeneration; diabetic retinopathy (DR); retinopathy of prematurity (ROP); retinitis pigmentosa (RP); uveitis, including Behçet's disease; and vitreoretinal lymphoma (VRL). However, in the first decade of this century, advances in biomedicine have provided new treatment strategies in the field of ophthalmology, particularly biologics that target vascular endothelial growth factor or tumor necrosis factor (TNF)-α. Furthermore, clinical trials on gene therapy specifically for patients with autosomal recessive or X-linked RP have commenced. The overall survival rates of patients with VRL have improved, owing to earlier diagnoses and better treatment strategies. However, some unresolved problems remain such as primary or secondary non-response to biologics or chemotherapy, and the lack of adequate strategies for treating most RP patients. In this review, we provide an overview of the immunological mechanisms of the eye under normal conditions and in several retinal disorders, including uveitis, DR, ROP, RP, and VRL. In addition, we discuss recent studies that describe the inflammatory responses that occur during the course of these retinal disorders to provide new insights into their diagnosis and treatment.

The Effectiveness of Brolucizumab and Aflibercept in Patients with Neovascular Age-Related Macular Degeneration

“…Ultimately, these authors determined that bevacizumab is a promising form of AMD therapy in patients, in whom an adequate response to treatment was not achieved using other VEGF inhibitors [ 37 ]. Observing drug resistance during molecular target therapies (anti-cytokine therapies) is nothing new, with this situation being observed in oncology, dermatology, and ophthalmology [ 38 , 39 ]. The observed difference in effectiveness between therapies based on aflibercept and brolucizumab is most likely the result of the different structures of the two inhibitors, the size of the molecule as well as the differing influence on signaling pathways dependent on VEGF.…”

Neuroinflammation as a Therapeutic Target in Retinitis Pigmentosa and Quercetin as Its Potential Modulator

“…The anti-inflammatory cytokine TGF-β induces a protective effect for deteriorating photoreceptors during the early stage of RP, which is mediated by microglia signaling [45]. However, due to the presence of the abnormal gene, the continuous activation of microglia results in dysregulated expression and secretion of pro-inflammatory markers, which eventually lead to cellular and tissue damage [46,47]. Indeed, as previously reported, increased levels of several pro-inflammatory cytokines, including IL-1β and IL-6, and an upsurge in the phagocytic activity of the microglia, were found in vitreal samples obtained from humans affected by RP [48,49].…”

Recent Advancements in the Medical Treatment of Diabetic Retinal Disease

“…Experimental DR models have identified CCR2 and CCR5 chemokines, which are expressed on the surface of monocytes. They are involved in signaling pathways associated with retinal vascular leakage, macrophage infiltration, and angiogenesis [138]. CCR2 has also been associated with regulating VEGF production.…”