Abstract
Purpose :
Glaucoma is a widespread optic neuropathy. Our previous studies have shown that intravitreal transplantation of human umbilical cord mesenchymal stem cells (UC-MSCs) reveal the neuroprotection in the microbead-injection induced ocular hypertension (OHT). The protective effects are related to the modulation of glial cells, but the mechanisms are unknown. The purpose of this study is to explore the potential signal mechanism toll-like receptor 4 (TLR4) pathway.
Methods :
OHT models were established with SD rats through intracameral injection of polystyrene microbeads. Thirty-six healthy adult rats were randomly divided into three groups: normal control, OHT model treated with intravitreal transplantation of UC-MSCs, or phosphate-buffered saline (PBS). Retinal protection was quantified by electroretinography (ERG) and optical coherence tomography (OCT). Apoptosis of retinal cell was detected by TUNEL assay and Bax expression 14 days following transplantation. The expression levels of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1(Iba-1) and TLR4 were assessed via immunohistochemistry, real-time quantitate PCR and Western blot. RNA and proteins were extracted 14 days following transplantation, and the expression levels of the following molecules were determined: myeloid differentiation factor 88 (MyD88), IL-1β, IL-6 and TNF-α.
Results :
ERG and OCT showed that intravitreal delivery of UC-MSCs significantly improved the recovery of retina function and morphology. TUNEL assay and the expression of Bax demonstrated that apoptosis of retinal cells were reduced by UC-MSCs 14 days following transplantation. Intravitreal UC-MSCs transplantation resulted decreased expression of GFAP, Iba-1, TLR4, MyD88, IL-1β, IL-6 and TNF-α 14 days following transplantation.
Conclusions :
Intravitreal transplantation of UC-MSCs revealed the retina protection in the microbead-injection induced OHT. UC-MSCs transplantation in OHT rats significantly improved retina function and morphology and was accompanied by the attenuation of inflammatory injury via suppression of glial and TLR4-mediated inflammatory pathway activation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.