Fig. 12.2  Distribution of green fluorescent protein-RSPCs in mice eye delivered using buffered saline and hyaluronan and methylcellulose hydrogels, assayed at 4 weeks posttransplantation. (a) Control transplantation in saline (b) transplantation in hyaluronan and methylcellulose hydrogels. Arrowheads indicate location of nuclei of transplanted cells

of the RSPCs in the subretinal space was found to be more even when delivered by the hydrogels than using saline solution (Fig. 12.2). Saline vehicle shows noncontiguous cellular integration and localized cellular groupings (inset) atop Bruch’s membrane (BM), suggesting cellular aggregation preor posttransplantation (Fig. 12.2a). Integration of the RSPCs delivered by the hydrogels with the RPE and formation of continuous banding patterns can also been seen (Fig. 12.2b).

12.6  Future Directions

In summary, hydrogels have potential to encapsulate and control release of a variety of drugs, such as antivascular endothelial growth factor (anti-VEGF), anti-inflammatory agents, and neuroprotective agents, and stem cells for treating retinal diseases. Formulation of these drugs in hydrogels can maintain the required local therapeutic level and thus minimize side effects. Intravitreal administrations (implantation and injection) of hydrogels can achieve most effective delivery of drugs to the retina, but the administration processes are invasive. Subconjunctival/transscleral administrations of hydrogels may be relatively less effective in terms of delivery of drugs to the retina, but less invasive than the intravitreal administration methods.

Future directions will be further developments of novel hydrogel materials for targeted and sustained delivery of one or more drugs to the retina for individualized medicine. Factors such as molecular size and conformation (for proteins) of drugs, interaction between drug and hydrogel materials, dose and duration of drug, and biocompatibility of hydrogel materials and their degradable components, need to be taken into account while designing a hydrogel for retinal drug delivery. Functional tests of drug/cell-encapsulated hydrogels by acuity, contrast sensitivity, ERG, microperimetry, fundus photography, and visual field measurement are important

end-point assessments of the performance of the hydrogel delivery systems. Nanoparticles have potential to cross biological barriers, be internalized by cells, functionalized with targeting, sensoring and reporting moieties, and easily administrated/injected, and thus hydrogels at nanoscale (nanogels) hold great promise for treating retinal diseases in the future.

Acknowledgments The work was supported by the NIH, JDRF and Coulter Foundation grants. TWG is the Jack and Nancy Turner Professor.

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