Evaluating retinal ganglion cell loss and dysfunction

Abstract

Retinal ganglion cells (RGC) bear the sole responsibility of propagating visual stimuli to the brain. Their axons, which make up the optic nerve, project from the retina to the brain through the lamina cribrosa and in rodents, decussate almost entirely at the optic chiasm before synapsing at the superior colliculus. For many traumatic and degenerative ocular conditions, the dysfunction and/or loss of RGC is the primary determinant of visual loss and are the measurable endpoints in current research into experimental therapies. To actually measure these endpoints in rodent models, techniques must ascertain both the quantity of surviving RGC and their functional capacity. Quantification techniques include phenotypic markers of RGC, retrogradely transported fluorophores and morphological measurements of retinal thickness whereas functional assessments include electroretinography (flash and pattern) and visual evoked potential. The importance of the accuracy and reliability of these techniques cannot be understated, nor can the relationship between RGC death and dysfunction. The existence of up to 30 types of RGC complicates the measuring process, particularly as these may respond differently to disease and treatment. Since the above techniques may selectively identify and ignore particular subpopulations, their appropriateness as measures of RGC survival and function may be further limited. This review discusses the above techniques in the context of their subtype specificity.

Bone Marrow-Derived Mesenchymal Stem Cells-Derived Exosomes Promote Survival of Retinal Ganglion Cells Through miRNA-Dependent Mechanisms

“…This is significantly higher neuroprotection than we and others previously observed with BMSC transplants . Although RBPMS stained more RGC than Brn3a (owing to the presence of Brn3a ‐ RGC subtypes ), the relative differences between groups remained the similar. Many BMSC do not survive the vitreal transplantation, particular as they lack the capacity to integrate into the retina and thus remain in the vitreous.…”

Optogenetic Stimulation of the Superior Colliculus Confers Retinal Neuroprotection in a Mouse Glaucoma Model

“…Together, these results demonstrate that preservation of somatic Brn3a immunoreactivity is linked with other aspects of RGC integrity. There also has been some controversy on the validity of Brn3a as an RGC marker after injury because of its downregulation before actual RGC death (Nuschke et al, 2015;Mead and Tomarev, 2016). Although the loss of Brn3a immunoreactivity precedes clearing of the RGC soma by phagocytosing cells, discrepancies between both measurements are only temporary and progress toward the same endpoint, indicating that Brn3a is a sensitive predictor of RGC integrity (Salinas-Navarro et al, 2010;Galindo-Romero et al, 2011).…”

A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture

“…6B), more sophisticated investigations of cell loss and optic nerve damage are necessary, as the use of Brn3a staining protocol may overestimate the actual loss of RGCs in this model. 51 In summary, a chronic mild IOP elevation can be induced in mice with the circumlimbal suture technique. This mild IOP elevation induced retinal changes largely independent of the initial IOP spike.…”