Abstract
Purpose :
Age related macular degeneration (AMD) remains a world leading cause of irreversible central vision loss. In cases of late stage (wet) AMD, growth of blood vessels into the retina can lead to severe blindness. Early stage (dry) AMD is more common but is generally untreatable. There is widespread agreement that RPE degeneration lies at the core of AMD pathogenesis. RPE cells are responsible for maintaining the blood-retinal microenvironment by clearing debris through phagocytosis, producing growth factors that maintain the photoreceptors, and orchestrating cellular responses to stimuli. As dysfunctional RPE tends to occur prior to photoreceptor damage, it is believed that replenishing the RPE may have protective benefits. However, cell delivery through bolus injection has proven to be inefficient due to leakage, aggregation, and cell death. While solid scaffolds are often too rigid and bulky for application in the layers of the retina. Therefore, a thermoresponsive injectable hydrogel scaffold is explored for its potential as an RPE cellular scaffold.
Methods :
As shown in Figure 1, a NIPAAm-based injectable previously developed in the Sheardown lab has been modified with RGDS, the adhesion peptide found in fibronectin of the extracellular matrix, on the N-acryloxysuccinimide copolymer. The modified material was characterized with nuclear magnetic resonance imaging (NMR). The viability of human retinal pigment epithelial cells (ARPE-19) cultured on the modified material is assessed.
Results :
NMR confirmed modification of N-acryloxysuccinimide indicative of RGDS binding. Preliminary results, shown in Figure 2, in which ARPE-19 cells were cultured on thin layers of the modified hydrogel display moderate viability following 48h culture on phosphate buffered saline (PBS) and fibronectin (FN) modified formulations. Cells did not display strong viability on the unmodified NIPAAm-based material.
Conclusions :
The development of a hydrogel scaffold primed for RPE cell adhesion has been characterized. Further studies exploring RPE integration and viability with the formed scaffold are required. If said scaffold can successfully be applied within the delicate layers of the retina, this hydrogel may present as a suitable method for cell delivery for various retinal pathologies such as AMD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.