Fibrosis and diseases of the eye

Abstract

Most diseases that cause catastrophic loss of vision do so as a result of abnormal angiogenesis and wound healing, often in response to tissue ischemia or inflammation. Disruption of the highly ordered tissue architecture in the eye caused by vascular leakage, hemorrhage, and concomitant fibrosis can lead to mechanical disruption of the visual axis and/or biological malfunctioning. An increased understanding of inflammation, wound healing, and angiogenesis has led to the development of drugs effective in modulating these biological processes and, in certain circumstances, the preservation of vision. Unfortunately, such pharmacological interventions often are too little, too late, and progression of vision loss frequently occurs. The recent development of progenitor and/or stem cell technologies holds promise for the treatment of currently incurable ocular diseases.

Figure 1. Schematic representation of the eye and principal types of retinal neovascularization and fibrosis/gliosis.

(A) The anterior segment of the eye, consisting primarily of the cornea and iris, is separated from the posterior segment by the lens. The posterior segment consists primarily of the vitreous and the retina. (B) The retina is a highly ordered, multilayered structure that is richly vascularized. Ischemic retinopathies, such as DR, can lead to ischemia and neovascularization on the surface of the retina. (C) In extreme cases, associated gliosis can lead to tractional retinal detachments. Reproduced with permission from the American Academy of Ophthalmology (122). (D) ARMD can be associated with subretinal neovascularization originating from the choriocapillaris, and this can lead to subretinal hemorrhage and fibrosis (E).

Figure 2. Cell-based therapy for the treatment of ischemic retinopathies.

Bone marrow–derived progenitor cells are injected into the posterior segment of the eye, where the injected cells localize to activated astrocytes. Both endothelial and myeloid progenitor cells localize to forming vasculature, where they can differentiate into endothelial cells or microglial cells, each participating in vasculotrophic rescue of ischemic blood vessels. Top far right, control-treated eye; bottom far right, progenitor cell–treated eye. Images reproduced from Nature Medicine (103) and Journal of Clinical Investigation (113).