Linking immune responses with fibrosis in allergic eye disease

Abstract

Purpose of review Here we explore an emerging theme in the literature, which is the role of dendritic cells in the causation of fibrosis. To fully appreciate this pathway to disease, we also review the most recent literature regarding dendritic cell biology as it pertains to ocular surface tissues. Based on this information we propose a unifying hypothesis for how dendritic cells may cause conjunctival fibrosis in the allergy setting. Recent Findings Work in models of airway remodeling and liver fibrosis has pointed to a potentially central role for dendritic cells in the pathobiology of fibrosis. Indeed, these cells are recognized as the most potent antigen-presenting cells, and as such activate of T lymphocytes that are pro-fibrotic under certain conditions. However, recent findings suggest a more direct role for dendritic cells, which opens up the possibility that a similar pathway may be relevant in the causation of conjunctival fibrosis, particularly in allergic eye disease. Summary Conjunctival fibrosis is a serious clinical concern, and is associated with chronic inflammation of the ocular surface tissue, such as in allergic eye disease. Dendritic cells are required in mediating allergic disease by activating pathologic T lymphocytes. However, recent findings pointing to a central role for dendritic cell in fibrosis may mean that these cells could also be contributing directly to conjunctival fibrosis. If so, furthering our understanding of dendritic cells could lead to the identification of novel and more effective therapeutic strategies to treat this pathology.

TGF-β-induced activation of conjunctival fibroblasts is modulated by FGF-2 and substratum stiffness

“…Wound healing mechanisms in the conjunctiva are involved in the pathology of various ocular diseases, and in the outcomes of ocular surgeries, including for pterygium and glaucoma [1][2][3][4][5]. Among the numerous cell types that contribute to wound closure, fibroblasts have been known to play a particularly important role by transdifferentiation into myofibroblasts.…”

Induction of Immune Surveillance of the Dysmorphogenic Lens

“…The interplay between the immune system, inflammation and fibrosis has been well-documented 13 , 63 , 64 . Recently, work has highlighted the role of the fibrocyte, a leukocyte subtype that expresses both CD45 and collagen I, in both wound healing and the fibrotic response 65 – 67 .…”

Rosiglitasone and ROCK Inhibitors Modulate Fibrogenetic Changes in TGF-β2 Treated Human Conjunctival Fibroblasts (HconF) in Different Manners

“…Among the alternative features of conjunctival barrier function, their permeability is also recognized to be an important factor for drug delivery to the posterior segment of the eye after the instillation of ocular drugs [ 2 ]. In terms of the clinical aspects of subconjunctival fibrosis, it has been suggested that the regulation of wound healing in the conjunctiva is of great importance in terms of the surgical outcomes of ocular surface-related diseases, such as pterygium and glaucoma [ 3 , 4 , 5 , 6 , 7 ]. In fact, conjunctival scarring at the operative site may adversely induce poor success rates in the subsequent trabeculectomy [ 8 , 9 ].…”