Efficacy of Osmoprotectants on Prevention and Treatment of Murine Dry Eye

Chen, Wei; Zhang, Xin; Li, Jinyang; Wang, Yu; Chen, Qi; Hou, Chao; Garrett, Qian

doi:10.1167/iovs.13-12081

Cited by 66 publications

(49 citation statements)

References 51 publications

(72 reference statements)

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“…In some cases in which there is extensive damage to the ocular surface caused by hypertonic-induced cell shrinkage and compromise of epithelial barrier function, tear film osmolarity increases can reach levels approaching those used in the current study [18]. Our results extend previous studies which showed in evaporative dry eye mouse models that osmolyte supplementation of artificial tears markedly improves ocular surface health by reducing inflammation and neovascularisation [1]. One of the osmolytes identified to have this therapeutic effect is L-carnitine since its intracellular uptake is stimulated during exposure to a hypertonic stress resulting in decreases in dry eye symptomology caused by cell volume shrinkage.…”

Section: Discussionsupporting

confidence: 85%

“…This realization of the importance of maintaining intracellular volume isotonicity with the external milieu to treat dry eye disease prompted efforts to identify osmolytes that could be of therapeutic value in countering presumed declines in corneal and conjunctival cell volume occurring in some types of dry eye disease. One of the organic osmolytes evaluated in dry eye mouse models, which improves ocular surface hydration is L-carnitine [1]. Its effectiveness stems from the fact that it is taken up into the cell interior by a Na + coupled co-transporter during exposure to a hypertonic stress and contributes to equilibrating the intracellular milieu with the external environment [2].…”

Section: Introductionmentioning

confidence: 99%

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L-Carnitine Reduces in Human Conjunctival Epithelial Cells Hypertonic-Induced Shrinkage through Interacting with TRPV1 Channels

Khajavi

Reinach

Skrzypski

et al. 2014

Cell Physiol Biochem

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Background/Aims: Ocular surface health depends on conjunctival epithelial (HCjE) layer integrity since it protects against pathogenic infiltration and contributes to tissue hydration maintenance. As the same increases in tear film hyperosmolarity described in dry eye disease can increase corneal epithelial transient receptor potential vanilloid type-1 (TRPV1) channel activity, we evaluated its involvement in mediating an osmoprotective effect by L-carnitine against such stress. Methods: Using siRNA gene silencing, Ca²⁺ imaging, planar patch-clamping and relative cell volume measurements, we determined if the protective effects of this osmolyte stem from its interaction with TRPV1. Results: TRPV1 activation by capsaicin (CAP) and an increase in osmolarity to ≈ 450 mOsM both induced increases in Ca²⁺ levels. In contrast, blocking TRPV1 activation with capsazepine (CPZ) fully reversed this response. Similarly, L-carnitine (1 mM) also reduced underlying whole-cell currents. In calcein-AM loaded cells, hypertonic-induced relative cell volume shrinkage was fully blocked during exposure to L-carnitine. On the other hand, in TRPV1 gene-silenced cells, this protective effect by L-carnitine was obviated. Conclusion: The described L-carnitine osmoprotective effect is elicited through suppression of hypertonic-induced TRPV1 activation leading to increases in L-carnitine uptake through a described Na⁺-dependent L-carnitine transporter.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

L-Carnitine Reduces in Human Conjunctival Epithelial Cells Hypertonic-Induced Shrinkage through Interacting with TRPV1 Channels

Khajavi

Reinach

Skrzypski

et al. 2014

Cell Physiol Biochem

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“…[54] Moreover, several injections are often needed to ensure optimal therapeutic drug levels at the site of action due to the short half-life of most ophthalmic drugs, thus increasing the risks of side effects and decreasing overall patient compliance. [17,55,56] Therefore, alternative methods to deliver ophthalmic formulations to the posterior segment that require less frequent dosing could be extremely beneficial for patients, with the advantage of avoiding the aforementioned complications related to repeated injections, and reducing the risk of rapid clearance.…”

Section: Routes Of Ocular Administrationmentioning

confidence: 99%

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

Ratay

Bellotti

Gottardi³

et al. 2017

Adv Healthcare Materials

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Dry eye disease (DED), age-related macular degeneration (AMD), and Uveitis are ocular diseases that significantly affect the quality of life of millions of people each year. In these diseases, the action of chemokines, pro-inflammatory cytokines, and immune cells drives a local inflammatory response that results in ocular tissue damage. Multiple therapeutic strategies have been developed to either address the symptoms or abate the underlying cause of these diseases. Herein, we will review the challenges to deliver drugs to the relevant location in the eye for each of these diseases as well as current and innovative therapeutic approaches that attempt to restore homeostasis within the ocular microenvironment.

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“…46 The osmoprotective effects of different agents (erythritol, glycerol, trehalose, betaine, L-carnitine) have been reported, [90][91][92] and emerging clinical trial data suggest a beneficial role for osmoprotectant solutions in patients with dry eye. 93,94 Recently, vitamin E-modified siliconehydrogel contact lenses to release betaine has been developed, 43 which is a well-known osmoprotectant, useful in protecting corneal cells from hypertonic stress damage.…”

Section: Osmoprotectantsmentioning

confidence: 99%

“…93,94 Recently, vitamin E-modified siliconehydrogel contact lenses to release betaine has been developed, 43 which is a well-known osmoprotectant, useful in protecting corneal cells from hypertonic stress damage. 91 In addition, the moisturizing agent, dexpanthenol, was also included in the contact lenses to facilitate hydratation and reduce water loss from the cell. Incorporation of the drugs was performed by simple soaking and the in vitro results showed that senofilcon A and narafilcon B contact lenses achieved release duration of approximately 10 hr for betaine and dexpanthenol with vitamin E loadings of 20% to 23%.…”

Section: Osmoprotectantsmentioning

confidence: 99%

Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review

Guzmán-Aránguez

Fonseca

Carracedo

et al. 2016

Eye &Amp; Contact Lens: Science &Amp; Clinical Practice

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Dry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses.

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Efficacy of Osmoprotectants on Prevention and Treatment of Murine Dry Eye

Cited by 66 publications

References 51 publications

L-Carnitine Reduces in Human Conjunctival Epithelial Cells Hypertonic-Induced Shrinkage through Interacting with TRPV1 Channels

L-Carnitine Reduces in Human Conjunctival Epithelial Cells Hypertonic-Induced Shrinkage through Interacting with TRPV1 Channels

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review

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