Nanotechnology in Retinal Disease: Current Concepts and Future Directions

Abstract

The retina is one of the most complex and extraordinary human organs affected by genetic, metabolic, and degenerative diseases, resulting in blindness for ∼1.3 million people in the United States and over 40 million people worldwide. This translates into a huge loss of productivity, especially among younger patients with inherited retinal diseases (IRDs) and diabetic retinopathy. Age-related macular degeneration accounts for 90% of all blindness cases worldwide. The prevalence of this condition is projected to reach over 5 million individuals over the next 3 decades. There are also >20 IRD phenotypes, affecting >2 million people worldwide. Nanobiotechnology uses nanotechnology for biological applications, making use of biological materials either conceptually or directly in the fabrication of new materials. Bionanotechnology, on the other hand, uses molecular biology for the purpose of creating nanostructures (ie, structures with at least 1 dimension <100 nm). Retinal applications of these technologies are developing at a rapid pace. This review includes the most current nanotechnological applications in retinal diagnostics, theranostics, drug delivery, and targeting, including the potential for nonviral vehicles such as liposomes, micelles, and dendrimers, which pose advantages over viral vectors in retinal drug delivery. Furthermore, we discuss current and future applications as surgical adjuncts and in regenerative medicine as they pertain to retinal disease. Structure and function of nanoparticles such as carbon nanotubules, quantum dots, and magnetic nanoparticles, as well as diagnostic technologies such as next-generation DNA sequencing and single-molecule bionanosensing, will also be discussed.

Keywords: biotechnology; drug delivery; gene therapy; nanotechnology; ophthalmology; retina.

FIG. 1.

Nanoscale comparison and types of nanotherapeutics used in drug delivery. Reprinted with permission from Maria Malamatari, MPhar, PhD, AFHEA.

FIG. 2.

Schematic representation of the pharmacological treatment of the neovascular AMD eye using PCL NPs as nanocarriers; a cell-penetrating peptide as a retinal penetration enhancer; and resveratrol and metformin as model drugs for synchronic attenuation of oxidative stress, inflammation, and angiogenesis in the diseased retina. Reprinted with permission from Nguyen et al. AMD, age-related macular degeneration; BM, Bruch's membrane; ELM, external limiting membrane; GCL, ganglion cell layer; ILM, inner limiting membrane; INL, inner nuclear layer; IPL, inner plexiform layer; NFL, nerve fiber layer; NPs, nanoparticles; ONL, outer nuclear layer; OPL, outer plexiform layer; PCL, poly(E-caprolactone); PL, photosensitive layer; PR, photoreceptors; RPE, retinal pigment epithelium.

FIG. 3.

SEM (top) and ESB-SEM (bottom) images of micropropellers. Scale bar = 500 nm. Reprinted with permission from Wu et al. ESB-SEM, energy selective backscatter-scanning electron microscope.