Search

Glaucoma, a major cause of irreversible blindness worldwide, is associated with elevated intraocular pressure (IOP) and progressive loss of retinal ganglion cells (RGCs) that undergo apoptosis. A mechanism for RGCs injury involves impairment of neurotrophic support and exogenous supply of neurotrophic factors has been shown to be beneficial. However, neurotrophic factors can have widespread effects on neuronal tissues, thus targeting neurotrophic support to injured neurons may be a better neuroprotective strategy. In this study, we have encapsulated LM22A-4, a small neurotrophic factor mimetic, into Annexin V-conjugated cubosomes (L4-ACs) for targeted delivery to injured RGCs in a model of acute IOP elevation, which is induced by acute IOP elevation. We have tested cubosomes formulations that encapsulate from 9% to 33% LM22A-4. Our data indicated that cubosomes encapsulating 9% and 17% LM22A-4 exhibited a mixture of Pn3m/Im3m cubic phase, whereas 23% and 33% showed a pure Im3m cubic phase. We found that 17% L4-ACs with Pn3m/Im3m symmetries showed better in-situ and in-vitro lipid membrane interactions than the 23% and 33% L4-ACs with Im3m symmetry. In vivo experiments showed that 17% L4-ACs targeted the posterior retina and the optic nerve head, which prevented RGCs loss and improved functional outcomes in a mouse model of acute IOP elevation. These results provide evidence that Annexin V-conjugated cubosomes-based LM22A-4 delivery may be a useful targeted approach to prevent the progression of RGCs loss in glaucoma. STATEMENT OF SIGNIFICANCE: Recent studies suggest that the therapy of effectively delivering neurotrophic factors to the injured retinal ganglion cells (RGCs) could promote the survival of RGCs in glaucoma. Our present work has for the first time used cubosomes as an active targeted delivery system and have successfully delivered a neuroprotective drug to the damaged RGCs in vivo. Our new cubosomal formulation can protect apoptotic cell death in vitro a

Harmful algal blooms, including those caused by the toxic diatom Pseudo-nitzschia, can have significant impacts on human health, ecosystem functioning and ultimately food security. In the current study we characterized a bloom of species of Pseudo-nitzschia that occurred in a south-eastern Australian oyster-growing estuary in 2019. Using light microscopy, combined with molecular (ITS/5.8S and LSU D1-D3 rDNA regions) and toxicological evidence, we observed the bloom to consist of multiple species of Pseudo-nitzschia including P. cf. cuspidata, P. hasleana, P. fraudulenta and P. multiseries, with P. cf. cuspidata being the only species that produced domoic acid (3.1 pg DA per cell). As several species of Pseudo-nitzschia co-occurred, only one of which produced DA, we developed a rapid, sensitive and efficient quantitative real-time polymerase chain reaction (qPCR) assay to detect only species belonging to the P. pseudodelicatissima complex Clade I, to which P. cf. cuspidata belongs, and this indicated that P. cuspidata or closely related strains may have dominated the Pseudo-nitzschia community at this time. Finally, using high resolution water temperature and salinity sensor data, we modeled the relationship between light microscopy determined abundance of P. delicatissima group and environmental variables (temperature, salinity, rainfall) at two sites within the estuary. A total of eight General Linear Models (GLMs) explaining between 9 and 54% of the deviance suggested that the temperature (increasing) and/or salinity (decreasing) data were generally more predictive of high cell concentrations than the rainfall data at both sites, and that overall, cell concentrations were more predictive at the more oceanic site than the more upstream site, using this method. We conclude that the combination of rapid molecular methods such as qPCR and real-time sensor data modeling, can provide a more rapid and effective early warning of harmful algal blooms of species of Pseudo-n