Aims
Age-related macular degeneration (AMD) is a neurodegenerative disease characterised by irreversible vision loss. In the degenerating retina, we have previously shown that a loss of extracellular vesicle (EV) bioavailability is correlated with key pathological features of AMD including photoreceptor cell death and large-scale inflammatory cascades. We therefore hypothesise that replenishment of EV from cells shown previously to have therapeutic benefits to the eye, such as bone marrow-derived mesenchymal stem cell EV (BM-MSC-EV), and their molecular cargo, may restore lost EV homeostatic communication pathways, slowing the progression of degeneration.
Methods
EV were isolated from BM-MSC cell culture supernatant using tangential flow filtration and size exclusion chromatography. EV or vehicle (PBS) were administered to the retina via intravitreal injection at a dose of 2.0x109 EV/μL (1μL) prior to degeneration using a well-established photo-oxidative damage model of retinal degeneration (100k lux bright white-light for 5 days). Electroretinography and optical coherence tomography were used to measure retinal function and morphology respectively following degeneration, while TUNEL and IBA-1+ immunohistochemistry was conducted on retinal cryosections to determine levels of cell death and inflammation.
Results
Compared to PBS-injected controls, delivery of BM-MSC EVs resulted in significantly higher retinal function, reduced presence of infiltration and activated microglia/macrophages as a measure of inflammation, and decreased levels of retinal cell death.
Conclusions
Our data supports BM-MSC-EV as a potential therapeutic EV source to slow the progression of retinal degeneration. These data suggest BM-MSC may provide a novel EV source for delivery of current and future therapeutics for retinal degeneration.