Effects of Varying Intranasal Treatment Regimens in ST266-Mediated Retinal Ganglion Cell Neuroprotection

Abstract

Introduction: Prior studies showed that intranasally administered ST266, a novel biological secretome of Amnion-derived Multipotent Progenitor cells containing multiple growth factors and anti-inflammatory cytokines, attenuated visual dysfunction and prevented retinal ganglion cell (RGC) loss in experimental optic neuritis. Long-term effects and dose escalation studies examined here have not been reported previously. Methods: Optic neuritis was induced in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE). EAE and control mice were treated once or twice daily with intranasal placebo/vehicle or ST266 beginning after onset of optic neuritis for either 15 days or continuously until sacrifice. Visual function was assessed by optokinetic responses (OKR). RGC survival and optic nerve inflammation and demyelination were measured. Results: Both once and twice daily continuous intranasal ST266 treatment from disease onset to 56 days post-EAE induction significantly increased OKR scores, decreased RGC loss, and reduced optic nerve inflammation and demyelination compared with placebo (saline, non-specific protein

Systemic Mesenchymal Stem Cell Treatment Mitigates Structural and Functional Retinal Ganglion Cell Degeneration in a Mouse Model of Multiple Sclerosis

“…This outcome might also be due to the nature of the MOG 35-55 EAE model, in which several studies aimed at RGC neuroprotection have indicated a huge variability in RGC survival from no to almost complete preservation. [40][41][42] An important factor on RGC survival in EAE models may be the timing of intervention and response of dosages, as nicely demonstrated by Wilmes et al 41 The group of Shindler et al reported a strong correlation on the magnitude RGC survival and the timepoint of corticosteroid intervention in the PLP-induced EAE model. 43 We used a single injection of MSC seven days after EAE induction and taking the half-life of MSC into consideration, a single MSC injection rather than multiple administrations might limit longer lasting neuroprotection as indicated by Payne et al 44 On the other hand, we see a robust rescue effect of the PERG amplitude, preservation of the RNFL, and notable mitigation of RGC loss, which is indicative of a sustained effect on the visual system.…”

“…This outcome might also be due to the nature of the MOG 35–55 EAE model, in which several studies aimed at RGC neuroprotection have indicated a huge variability in RGC survival from no to almost complete preservation. 40 – 42 An important factor on RGC survival in EAE models may be the timing of intervention and response of dosages, as nicely demonstrated by Wilmes et al . 41 The group of Shindler et al .…”

Intranasal Administration of Mesenchymal Stem Cell Secretome Reduces Hippocampal Oxidative Stress, Neuroinflammation and Cell Death, Improving the Behavioral Outcome Following Perinatal Asphyxia

“…Intranasal administration of the secretome from multipotent stem/progenitor cells has been proposed as a strategy for treating other diseases, such as retinal ganglion cell loss [ 75 , 76 ], multiple sclerosis [ 77 ], Alzheimer’s disease [ 78 ], and Parkinson’s disease [ 79 ], including recently, alcohol and nicotine consumption [ 58 ]. In all these models, MSC-S has shown anti-inflammatory and antioxidant effects, also improving neurodevelopment and memory function.…”

Inflammation in the anterior visual pathway in multiple sclerosis: what do the animal models teach us?

“…Since EAE is the most commonly used animal model for MS with a predominant inflammatory component, it is regularly used to test the effects of new anti-inflammatory treatment strategies and to better understand the pathophysiological mechanisms of on-and off-label drugs. Recent structural and functional measurements such as OCT, VEP, optomotor response, optokinetic response, and electroretinogram (ERG), thereby allow a sensitive longitudinal evaluation of structure and function [79,82,96,106,113,114,[122][123][124][125][126] . Advantages and disadvantages of these in vivo readouts, which are increasingly being used in animal models, are described in Table 2.…”