Photo-induced destruction of protein aggregates and liquefaction of vitreous humour using nanobubbles generating liposomes
Pouria Ramezani (PhD fellow funded by the PRC) - Ghent University
With aging there is progressive aggregation of collagen in the vitreous. When collagen aggregates (‘floaters’) become too large they block sight, which negatively impacts vision. Photo-ablation, the treatment of the aggregates with strong (nanosecond) pulsed-laser, is a current practice. Though significant room remains for a more effective and safer treatment. This project aims to destroy aggregates through the combined use of (i) laser pulses of very low energy and (ii) indocyanine green (ICG), being FDA-approved for use in ophthalmology.
We observed that ICG spontaneously accumulates on collagen aggregates (in vitro) and that up-on laser illumination vapor nanobubbles (VNBs) arise which mechanically destroy the aggregates. However, ICG can penetrate into the retina and induce phototoxicity. Encapsulating ICG into liposomes with lower penetration in the retina is therefore a major focus of this project.
This project aims to explore to which extent ICG or ICG aggregates encapsulated in liposomes which bind to floaters, allows to destroy the floaters in vivo using low energetic laser pulses. Also, as a result of (partial) liquefaction of vitreous, the vitreous cortex often starts to detach from the retina in elderly (post-vitreous detachment; PVD). Incomplete PVD can lead to retinal tears which tremendously impact vision. An approach to detach the vitreous completely from the retina would be beneficial. Current treatment relies on vitrectomy or intravitreal injection of enzymes such ocriplasmin. This project will also explore ICG-loaded liposomes – able to generate VNBs in the vitreous – for the purpose of local (and safe) liquefaction of the vitreous.1)2)
Benefit for the community
After the publication of our first study in ACS nano and in Nature Nanotechnology, we have been contacted and solicited by many patients with vitreous opacities. We therefore decided to disseminate our results in Facebook groups. I also proposed Q&A sessions with patients to keep them updated about our research on vitreous opacities. We will continue to communicate and valorize our research through these platforms. To communicate our research to both patients as well as ophthalmologists/ ocular surgeons, we will disseminate results through a platform Dr. Sebag recently set (www.vdmresearch.org/).
Our work has also tight links with the international floater association (www.thefloatersociety.com) led by Prof. M.J. Tassignon. Attractive as well is that we have been contacted by journalists for interviews in EOS Wetenschap and C&EN being the magazine of ACS (American Chemical Society). We envision a strong impact of the submitted project and thus hope to communicate it to non-experts via the media described above. For the lipid community, we aim at showing for the first time that liposomes loaded with dyes such as ICG can generate vapor nanobubbles. While this concept has been shown mainly with plasmonic nanoparticles, concerns about their toxicity after injection in the vitreous remain. Therefore, exploring ‘organic’ nanoparticles as fuel for vapor nanobubbles (VNBs) would pave the way for a safer manipulation of light in the vitreous and more generally in ophthalmology.