The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders

Abstract

Inherited retinal dystrophies (IRDs) as well as genetically complex retinal phenotypes represent a heterogenous group of ocular diseases, both on account of their phenotypic and genotypic characteristics. Therefore, overlaps in clinical features often complicate or even impede their correct clinical diagnosis. Deciphering the molecular basis of retinal diseases has not only aided in their disease classification but also helped in our understanding of how different molecular pathologies may share common pathomechanisms. In particular, these relate to dysregulation of two key processes that contribute to cellular integrity, namely extracellular matrix (ECM) homeostasis and inflammation. Pathological changes in the ECM of Bruch’s membrane have been described in both monogenic IRDs, such as Sorsby fundus dystrophy (SFD) and Doyne honeycomb retinal dystrophy (DHRD), as well as in the genetically complex age-related macular degeneration (AMD) or diabetic retinopathy (DR). Additionally, complement system dysfunction and distorted immune regulation may also represent a common connection between some IRDs and complex retinal degenerations. Through highlighting such overlaps in molecular pathology, this review aims to illuminate how inflammatory processes and ECM homeostasis are linked in the healthy retina and how their interplay may be disturbed in aging as well as in disease.

Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases

“…Although the molecular mechanisms underlying FNDs development remain unclear, extracellular matrix (ECM) homeostasis and immunity dysfunction are thought to be involved in pathological fundus neovascularization [ 153 ]. Clinical and preclinical studies have highlighted the roles of microglia and macrophages in disease progression and neovascularization [ 154 – 165 ].…”

The Role of Diabetic Choroidopathy in the Pathogenesis and Progression of Diabetic Retinopathy

“…The deposition of extracellular matrix (ECM) constituents, including collagen IV, fibronectin, and laminin, contributes to the development of a thicker BM [ 45 , 46 ]. An altered ECM remains an early and crucial event in DR, leading to fibrosis and increased vascular stiffness and permeability [ 47 ]. The alterations at the ECM level have demonstrated to influence the leukocyte adhesion leading to leukostasis [ 48 , 49 ].…”