Abstract
Purpose :
Glaucoma is an optic neuropathy characterized by gradual retinal ganglion cell (RGC) loss. RGCs are the output neurons of the retina and are responsible for processing and transferring visual information from the eye to recipient brain areas. Despite intensive research on neuroprotective therapies to prevent neuronal loss (and subsequent blindness), there is no clinical use of potential neuroprotective therapies for glaucoma. One of the studied treatment tools that has shown promise is miRNA therapeutics. However, miRNAs are unstable, negatively charged molecules, and can be easily digested by enzymes. To achieve efficient delivery of miRNAs, there is a need for a system that can deliver miRNAs to target cells at an efficient dose.
Extracellular vesicles (EV) are nanosized, lipid bilayer structures that provide communication between cells. Their liposome-like structures and surface receptors emphasize the capability by which EVs can deliver cargo to targeted cell groups. In this study, we hypothesised that R-28 derived EVs might be a new therapeutic and drug delivery system for RGC degeneration in glaucoma.
Methods :
In our current project, we isolated EVs from a retinal cell line (R-28 cell line) using differential ultracentrifuge and chracterized with NTA and western blotting. Isolated EVs were tested for neuroprotective potential in rat primary RGC culture. We tested also EVs in vivo glaucoma model. Following this, we explored R-28 derived EVs in terms of retinal drug delivery systems.
Results :
These data provide important information about the therapeutic and drug delivery system potential of R-28 derived EVs for retinal diseases. According to our results, R-28 derived EVs improved RGC survival in rat primary cell culture and human embryonic stem cell derived RGCs. Moreover, it provided RGC protection in the chronic microbead glaucoma model. We also observed alterations in miRNA content in RGCs. Moreover, we elucidated R-28 derived EV’s drug delivery potential. We also determined R-28 derived EVs drug release kinetics in the rodent vitreous humor and demonstrated their specificity for retinal cell types.
Conclusions :
Consequently, R-28 derived EVs have therapeutic potential for RGC degeneration in glaucoma and the potential to be an ideal drug delivery system for the retina.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.