Vascular Regeneration for Ischemic Retinopathies: Hope from Cell Therapies

Abstract

Retinal vascular diseases, such as diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, ocular ischemic syndrome and ischemic optic neuropathy, are leading causes of vision impairment and blindness. Whilst drug, laser or surgery-based treatments for the late stage complications of many of these diseases are available, interventions that target the early vasodegenerative stages are lacking. Progressive vasculopathy and ensuing ischemia is an underpinning pathology in many of these diseases, leading to hypoperfusion, hypoxia, and ultimately pathological neovascularization and/or edema in the retina and other ocular tissues, such as the optic nerve and iris. Therefore, repairing the retinal vasculature may prevent progression of ischemic retinopathies into late stage vascular complications. Various cell types have been explored for their vascular repair potential. Endothelial progenitor cells, mesenchymal stem cells and induced pluripotent stem cells are studied for their potential to integrate with the damaged retinal vasculature and limit ischemic injury. Clinical trials for some of these cell types have confirmed safety and feasibility in the treatment of ischemic diseases, including some retinopathies. Another promising avenue is mobilization of endogenous endothelial progenitors, whereby reparative cells are moved from their niche to circulating blood to target and home into ischemic tissues. Several aspects and properties of these cell types have yet to be elucidated. Nevertheless, we foresee that cell therapy, whether through delivery of exogenous or enhancement of endogenous reparative cells, will become a valuable and beneficial treatment for ischemic retinopathies. ARTICLE HISTORY

Therapeutic Potential of Endothelial Colony-Forming Cells in Ischemic Disease: Strategies to Improve their Regenerative Efficacy

“…The main leading cause of visual impairment is represented by ischemic retinopathies, such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity, which are all featured by vasodegeneration [ 74 ]. Preclinical evidence shows that ECFC transplantation could provide a promising approach to treat such disorders [ 21 ].…”

Mesenchymal Stromal Cells Promote Retinal Vascular Repair by Modulating Sema3E and IL-17A in a Model of Ischemic Retinopathy

“…However, anti-VEGF agents do not facilitate revascularization of the retina, resulting in undesired outcome (Ghasemi Falavarjani and Nguyen, 2013;Bracha et al, 2018;Low et al, 2019). Lately, adult stem-cell based therapies have emerged as alternative therapeutic avenues to treat IRs (Dorrell et al, 2004;Sivan et al, 2016;Bertelli et al, 2020). In particular, Mesenchymal Stem/Stromal Cells (MSCs) are a most promising modality for the treatment of ocular diseases (Joe and Gregory-Evans, 2010;Ding et al, 2017) because of their remarkable immunomodulatory and angiogenic capacities (Singer and Caplan, 2011;Nassiri and Rahbarghazi, 2013;Tao et al, 2016;Weiss and Dahlke, 2019); correspondingly, MSCs exert protective functions on brain and retinal neurons (Harrell et al, 2019;Zhang et al, 2020).…”

Therapeutic Potential of Endothelial Colony Forming Cells in Ischemic Disease: Strategies to Improve Their Regenerative Efficacy

“…Ischemic retinopathy The main leading cause of visual impairment is represented by ischemic retinopathies, such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity, which are all featured by vasodegeneration [74]. Pre-clinical evidence shows that ECFC transplantation could provide an alternative yet promising approach for such disorders [21].…”