Abstract
Purpose :
To evaluate the safety of human adipose-derived stem cells (ADSCs) and ADSCs-derived conditioned medium (ADCM) in normal rats and the therapeutic effects in a rat model of retinal degeneration by using Royal College of Surgeons (RCS) rats.
Methods :
The ADSC and ADCM were administrated through intravitreal, subretinal, subtenon injections or PBS respectively in wild type Wistar rats and in RCS rats. Daily immunisuppresive drug of cyclosporin was given to decrease immunereactions. The optic coherence tomography (OCT), electroretinogram (ERG) and Immunohistochemistry (IHC) were used to evaluate the morphology and visual function. Rats were sacrificed at 8 weeks after injections.
Results :
The OCT images demonstrated that subtenon injection of ADSCs resulted in a decrease in inner nuclear layer (INL) thickness compared to PBS administration (p<0.05). The ERG analysis also proved that subtenon injection of ADSCs led to an amplitude reduction in b wave compared to PBS treatment (p<0.05). Subretinal and intravitreal injections of ADSCs also induced retinal inflammation. Intravitreal, subretinal, and subtenon injections of ADSCs in the RCS rat resulted in severe adverse effects such as retinal inflammation, Graft-versus-host disease, growth retardation, and even death. However, the intravitreal injection of ADCM can effectively reduce the decreases of INL thickness and improve the a and b wave amplitudes of ERG in the RCS rats compared to PBS treatment.
Conclusions :
Intraocular or subtenon injection of ADSCs may not be safe stem cell therapies in the rat model of retinal degeneration and the intravitreal injection of ADCM may be a potential trial for patients with retinal degeneration in the future.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.