What can we learn about stroke from retinal ischemia models?

Abstract

Retinal ischemia is a very useful model to study the impact of various cell death pathways, such as apoptosis and necrosis, in the ischemic retina. However, it is important to note that the retina is formed as an outpouching of the diencephalon and is part of the central nervous system. As such, the cell death pathways initiated in response to ischemic damage in the retina reflect those found in other areas of the central nervous system undergoing similar trauma. The retina is also more accessible than other areas of the central nervous system, thus making it a simpler model to work with and study. By utilizing the retinal model, we can greatly increase our knowledge of the cell death processes initiated by ischemia which lead to degeneration in the central nervous system. This paper examines work that has been done so far to characterize various aspects of cell death in the retinal ischemia model, such as various pathways which are activated, and the role neurotrophic factors, and discusses how these are relevant to the treatment of ischemic damage in both the retina and the greater central nervous system.

Prothymosin‐alpha preconditioning activates TLR4–TRIF signaling to induce protection of ischemic retina

“…; Neroev et al . ; Iadecola and Anrather ; D'Onofrio and Koeberle ; Rodrigo et al . ; Benakis et al .…”

“…Cerebrovascular or retinal ischemia refers to substantial damage to, or death of, neuronal cells and the neurological dysfunction resulting from the initiation of multiple fatal mechanisms including the up-regulation and secretion of cytotoxic molecules such as cytokines and chemokines from glial cells (Osborne et al 2004;Lakhan et al 2009;Neroev et al 2010;Iadecola and Anrather 2011;D'Onofrio and Koeberle 2013;Rodrigo et al 2013;Benakis et al 2014). Among such injurious mechanisms, toll-like receptor 4 (TLR4) plays a key role in worsening brain and retinal ischemic damage through the production of cytotoxic mediators, and TLR4 knock-out (TLR4 À/À ) mice exhibit partial neuroprotection against cerebral ischemia (Caso et al 2007;Arslan et al 2010;Hyakkoku et al 2010;Wang et al 2011;Qi et al 2014;Shichita et al 2014;Hua et al 2015).…”

Experimental Animal Models for Retinal and Choroidal Diseases

“…Retinal ischemia, a common cause of irreversible visual impairment, is associated with various retinal diseases such as ischemic optic neuropathies, obstructive retinopathies, carotid occlusive disorders, diabetic retinopathy and glaucoma [159][160][161][162][163][164]. Retinal ischemia occurs when there is an imbalance between the blood supply and the metabolic requirements of the retina and it results in cellular death.…”

“…As the blood supply to retina and choroid is too similar to that in humans, the rats are frequently used for the studies in RIR models. The main methods of the induction of retinal ischemia in the animal include the raising the IOP, middle cerebral artery (MCA) occlusion, chronic carotid ligation, photothrombosis or photocoagulation of retinal vessels, central retinal artery (CRA) occlusion, and intravitreal or intravenous endothelin administration [159][160][161][162][163][164]. Filamentous MCA occlusion is one of most commonly used method both focal cerebral and retinal ischemia models in rodents because the ophthalmic artery and is proximal to the origin of the MCA [162,163].…”

Maintenance and modification of mesenchymal stromal cell immunosuppressive phenotype

“…The inner layer of the retina, were the RGC cell bodies reside, have been demonstrated to be particularly sensitive to hypoxia 79 , thus the ability to salvage RGC in the setting of I/R is critical if some degree of vision is to be preserved. In addition, retinal I/R injury not only resembles various ophthalmologic disorders causing visual impairment such as ischemic optic neuropathies and glaucoma, but also recapitulates many aspects of CNS injury, in particular stroke [80][81][82] . The analogy in the pathobiology with respect to hypoxia, oxidative stress and inflammation makes the 91 .…”