Elsevier

Mayo Clinic Proceedings

Volume 88, Issue 12, December 2013, Pages 1480-1490
Mayo Clinic Proceedings

Symposium on regenerative medicine
Regenerative Nanomedicine for Vision Restoration

https://doi.org/10.1016/j.mayocp.2013.05.025Get rights and content

Abstract

Herein, we discuss recent applications of nanotechnology to ophthalmology, including nanoparticles for drug, gene, and trophic factor delivery; regenerative medicine (in the areas of optogenetics and optic nerve regeneration); and diagnostics (eg, minimally invasive biometric monitoring). Specific applications for the management of choroidal neovascularization, retinal neovascularization, oxidative damage, optic nerve damage, and retinal degenerative disease are considered. Nanotechnology will play an important role in early- and late-stage interventions in the management of blinding diseases.

Section snippets

Nanoparticles for Drug, Gene, and Trophic Factor Delivery

Loss of oxygen or its electrons alters the oxidation state of cerium oxide nanoparticles (“nanoceria”) and creates defects in their lattice structure. As their size decreases, nanoceria (3-5 nm in diameter) exhibit more oxygen vacancies in their crystal structure, which can allow them to function as antioxidants. Chen et al9 found that intravitreal injection of nanoceria prevents light-induced photoreceptor damage in rodents, even if injected after the initiation of light damage.

Regenerative Medicine: Optogenetics and Optic Nerve Regeneration

Optogenetics involves the use of light-sensitive ion channels (vs electrodes) to make neurons light sensitive. This approach to visual rehabilitation has been reviewed extensively.6, 7, 8, 40 Stimulation of RGCs or bipolar cells provides an alternative approach to retinal cell stimulation in lieu of that provided by the retinal prosthesis.41 In contrast to the currently available retinal prosthesis, optogenetics has the potential for minimally invasive neuronal stimulation with high spatial

Biomaterials and Regenerative Medicine

Retinal progenitor cells can be delivered to the eye, migrate to correct regions in the retina, and differentiate into photoreceptors with appropriate markers and morphologic features. It is essential, however, that these photoreceptors can transmit a signal centrally for vision perception. Pearson et al53 used Gnat1–/– mice, which lack rod function, to address this issue. They found that transplanted rod precursors could form classic triad synaptic connections with second-order bipolar and

Diagnostics

Some ways in which nanotechnology has improved diagnostic imaging have been reviewed previously.4 Progress in this area continues. For example, monitoring active angiogenesis in neovascular eye diseases is essential for gauging a patient's disease progression and response to treatment.69 Thus far, no in vivo imaging methods are available to label active angiogenesis specifically. Hua et al70 demonstrated that cationic (but not neutral) liposomes labeled with indocyanine green could, with high

Barriers to Clinical Application

Several obstacles to the incorporation of nanotechnology into medicine are recognized.4 The biodistribution of nanoparticles and their persistence in tissues despite immune surveillance is a concern.76 Safe bionanomanufacturing techniques also must be identified. This issue is particularly relevant when scaling up production for commercial distribution of products. Clean room processes similar to those used for semiconductor device manufacture may be needed in some cases. Although

Conclusion

Nanomedicine has already had an impact in the areas of biopharmaceuticals (eg, glaucoma drugs and neurotrophic factors), implantable materials (eg, tissue regeneration scaffolds), and diagnostic tools (eg, IOP monitors) in ophthalmology. The examples provided herein demonstrate that nanotechnology will play an important role in early- and late-stage interventions in the management of blinding diseases. Nanotechnology already has been applied to the measurement and treatment of different disease

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    Grant Support: This study was supported, in part, by Research to Prevent Blindness Inc (M.A.Z., R.R.), the Joseph DiSepio AMD Research Fund (M.A.Z.), and the HRH Prince Khalid bin Abdulla al Saud Research Fund of the New York Eye and Ear Infirmary (R.R.).

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