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Nanomedicine approaches for corneal diseases.

Chaurasia SS, Lim RR, Lakshminarayanan R, Mohan RR - J Funct Biomater (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology Veterinary Medicine & Surgery, Columbia, MO 65211, USA. chaurasias@missouri.edu.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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jfb-06-00277-f001: 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.

Mentions: Stromal wound healing in the cornea is a complex process (Figure 1), controlled by the interactions and signaling between epithelial and stromal cells. Keratocytes, present beneath the epithelium in the corneal stroma, exhibit relatively low levels of activity and are considered quiescent in the adult cornea [44,45,46]. Insult to corneal stroma triggers inflammatory response, cell proliferation, and secretion of several growth factors, chemokines, extracellular and matricellular proteins. The activation of inflammatory cells close to the site of wound, which are cleared by apoptosis in the initial phase of wound healing, limits the inflammatory response and loss of intracellular components, thus demonstrating effective wound healing. A previous study suggests that vimentin+ and desmin+ stromal cells play an essential role in the early and intermediate stages of the formation of myofibroblasts (Figure 2) during corneal wound healing [14]. These myofibroblasts produce high levels of collagen, hyaluronan and biglycan to form a disorganized and opaque cornea. Several matrix metalloproteases (MMPs) and tissue inhibitors of matrix metalloproteases (TIMPs) are released during wound healing and they contribute in matrix remodeling by removing irregular matrix and reinstating newer ECM. Recently, it has been reported that Hevin, a matricellular protein, plays a role in the modulation of corneal wound healing in a mouse model [47]. It is transiently expressed in the early stages of corneal wound healing and its functional loss predisposes injured cornea to chronic inflammation and fibrosis (Figure 3). Thus, proper disposal of the transient matrix and its replacement by organized and mature ECM (with matricellular proteins) forms an integral part of the corneal transparency. Any disorganization or the non-removal of the degenerate matrix can lead to aberrant wound healing in the corneal stroma and, hence, impaired vision.


Nanomedicine approaches for corneal diseases.

Chaurasia SS, Lim RR, Lakshminarayanan R, Mohan RR - J Funct Biomater (2015)

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.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493512&req=5

jfb-06-00277-f001: 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.
Mentions: Stromal wound healing in the cornea is a complex process (Figure 1), controlled by the interactions and signaling between epithelial and stromal cells. Keratocytes, present beneath the epithelium in the corneal stroma, exhibit relatively low levels of activity and are considered quiescent in the adult cornea [44,45,46]. Insult to corneal stroma triggers inflammatory response, cell proliferation, and secretion of several growth factors, chemokines, extracellular and matricellular proteins. The activation of inflammatory cells close to the site of wound, which are cleared by apoptosis in the initial phase of wound healing, limits the inflammatory response and loss of intracellular components, thus demonstrating effective wound healing. A previous study suggests that vimentin+ and desmin+ stromal cells play an essential role in the early and intermediate stages of the formation of myofibroblasts (Figure 2) during corneal wound healing [14]. These myofibroblasts produce high levels of collagen, hyaluronan and biglycan to form a disorganized and opaque cornea. Several matrix metalloproteases (MMPs) and tissue inhibitors of matrix metalloproteases (TIMPs) are released during wound healing and they contribute in matrix remodeling by removing irregular matrix and reinstating newer ECM. Recently, it has been reported that Hevin, a matricellular protein, plays a role in the modulation of corneal wound healing in a mouse model [47]. It is transiently expressed in the early stages of corneal wound healing and its functional loss predisposes injured cornea to chronic inflammation and fibrosis (Figure 3). Thus, proper disposal of the transient matrix and its replacement by organized and mature ECM (with matricellular proteins) forms an integral part of the corneal transparency. Any disorganization or the non-removal of the degenerate matrix can lead to aberrant wound healing in the corneal stroma and, hence, impaired vision.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology Veterinary Medicine & Surgery, Columbia, MO 65211, USA. chaurasias@missouri.edu.

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.

No MeSH data available.


Related in: MedlinePlus