Nanomedicine approaches for corneal diseases

Abstract

Corneal diseases are the third leading cause of blindness globally. Topical nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, antibiotics and tissue transplantation are currently used to treat corneal pathological conditions. However, barrier properties of the ocular surface necessitate high concentration of the drugs applied in the eye repeatedly. This often results in poor efficacy and several side-effects. Nanoparticle-based molecular medicine seeks to overcome these limitations by enhancing the permeability and pharmacological properties of the drugs. The promise of nanomedicine approaches for treating corneal defects and restoring vision without side effects in preclinical animal studies has been demonstrated. Numerous polymeric, metallic and hybrid nanoparticles capable of transporting genes into desired corneal cells to intercept pathologic pathways and processes leading to blindness have been identified. This review provides an overview of corneal diseases, nanovector properties and their applications in drug-delivery and corneal disease management.

Figure 1

Schematic representation of the corneal wound healing mechanism. (1) Corneal injury results in the loss of basement membrane; (2) Release of pro-inflammatory cytokines into the anterior stroma; (3) Activation of quiescent keratocytes to fibroblast; (4) Growth factor released from the epithelium & TGFβ result in trans-differentiation of fibroblast to myofibroblast, the repair phenotype; (5) Under normal physiological condition, myofibroblasts undergo apoptosis following repair to the cornea; (6) In pathological conditions, myofibroblasts secrete irregular matrix; (7) Clinical observation of corneal haze in the anterior stroma.

Figure 2

Expression of vimentin and desmin during corneal wound healing. Rabbit underwent −9D photorefractive keratectomy (PRK). Corneas were stained with αSMA (myofibroblast marker) with vimentin (A) or desmin (B) four-week post-surgery. ^, vimentin+; *, vimentin+ & αSMA+; Δ, desmin+; ↑, desmin+ & αSMA+. Scale bar = 25 μm. Reprinted from [14]. Copyright Elsevier 2009.

Figure 3

Hevin plays a critical role in corneal wound healing. Hevin is not expressed in C57BL/6J naïve mouse cornea (A,B). Hevin (^) is upregulated in irregular phototherapeutic keratectomy (IrrPTK) mice one week post-surgery (C) and decrease in expression of Hevin two weeks post-surgery (D). Scale bar = 25 μm. Reprinted from [47]. Copyright PLOS 2013.

Figure 4

Schematic diagram depicting nanomedicine techniques available for corneal diseases.

Figure 5

Treatment of corneal haze with nanoparticles. Corneal haze was developed in rabbit corneas using −9.0 diopter photorefractive keratectomy (PRK) with excimer laser. Representative stereomicroscopy (A,B) and slit-lamp (C,D) images of laser-ablated rabbit corneas that received a single 5 min topical application of PEI2-AuNPs nanoparticle transfection solution without BMP7 (A,C) or with BMP7 expressing gene (B,D) obtained four weeks after PRK.