Impact of pesticides on ocular surface using an innovative in vitro design

Corneal cross-linking is nowadays the most used strategy for the treatment of keratoconus and recently it has been exploited for an increasing number of different corneal pathologies, from other ectatic disorders to keratitis. The safety of this technique has been widely assessed, but clinical complications still occur. The potential effects of cross-linking treatment upon the limbus are incompletely understood; it is important therefore to investigate the effect of UV exposure upon the limbal niche, particularly as UV is known to be mutagenic to cellular DNA and the limbus is where ocular surface tumors can develop. The risk of early induction of ocular surface cancer is undoubtedly rare and has to date not been published other than in one case after cross-linking. Nevertheless it is important to further assess, understand, and reduce where possible any potential risk. The aim of this review is to summarize all the reported cases of a pathological consequence for the limbal cells, possibly induced by cross-linking UV exposure, the studies donein vitroorex vivo, the theoretical bases for the risks due to UV exposure, and which aspects of the clinical treatment may produce higher risk, along with what possible mechanisms could be utilized to protect the limbus and the delicate stem cells present within it.

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Preserved and Unpreserved 12 Anti-allergic Ophthalmic Solutions and Ocular Surface Toxicity: In Vitro Assessment in Four Cultured Corneal and Conjunctival Epithelial Cell Lines

Biocontrol Science ◽

10.4265/bio.15.143 ◽

2010 ◽

Vol 15 (4) ◽

pp. 143-148 ◽

Cited By ~ 8

Author(s):

MASAHIKO AYAKI ◽

ATSUO IWASAWA ◽

SHIGEO YAGUCHI ◽

RYOHEI KOIDE

Keyword(s):

Epithelial Cell ◽

Cell Lines ◽

Ocular Surface ◽

Conjunctival Epithelial Cell ◽

Epithelial Cell Lines ◽

In Vitro Assessment ◽

Toxicity In Vitro ◽

Ophthalmic Solutions

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Exposure to Traffic-Related Particulate Matter 2.5 Triggers Th2-Dominant Ocular Immune Response in a Murine Model

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17082965 ◽

2020 ◽

Vol 17 (8) ◽

pp. 2965

Author(s):

Hyun Soo Lee ◽

Sehyun Han ◽

Jeong-Won Seo ◽

Ki-Joon Jeon

Keyword(s):

Immune Response ◽

Particulate Matter ◽

Murine Model ◽

Ocular Surface ◽

Immunological Response ◽

Inflammatory Cells ◽

Th2 Cells ◽

Fluorescein Staining ◽

Serum Ige

Ambient particulate matter (PM), a major component of air pollution, aggravates ocular discomfort and inflammation, similarly to dry eye disease (DED) or allergies. However, the mechanism(s) by which PM induces the ocular inflammatory response is unknown. This study investigated the immunological response of traffic-related fine particulate matter (PM2.5) on the ocular surface in a murine model. C57BL/6 mice were exposed by topical application to PM2.5 or vehicle for 14 days to induce experimental environmental ocular disease. Corneal fluorescein staining and the number of ocular inflammatory cells were assessed in both groups. The expression of IL-1β, IL-6, tumor necrosis factor (TNF)-α, and mucin 5AC (MUC5AC) in the ocular surface were evaluated by real-time PCR. An immunohistochemical assay evaluated apoptosis and goblet cell density. ELISA was used to determine the levels of serum IgE and cytokines of Type 1 helper (Th1) and Type 2 helper (Th2) cells after in vitro stimulation of T cells in the draining lymph nodes (LNs). Exposure to traffic-related PM2.5 significantly increased corneal fluorescein staining and cellular toxicity in the corneal epithelium compared with the vehicle control. A significant increase in the number of CD11b+ cells on the central cornea and mast cells in the conjunctiva was observed in the PM2.5 group. Exposure to PM2.5 was associated with a significant increase in the corneal or conjunctival expression of IL-1β, IL-6, TNF, and MUC5AC compared to the vehicle, and increased maturation of dendric cells (DCs) (MHC-IIhighCD11c+) in draining LNs. In addition, PM2.5 exposure increased the level of serum IgE and Th2 cytokine production in draining LNs on day 14. In conclusion, exposure to traffic-related PM2.5 caused ocular surface damage and inflammation, which induced DC maturation and the Th2-cell-dominant allergic immune response in draining LNs.

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Recent Advances in the Design of Topical Ophthalmic Delivery Systems in the Treatment of Ocular Surface Inflammation and Their Biopharmaceutical Evaluation

Pharmaceutics ◽

10.3390/pharmaceutics12060570 ◽

2020 ◽

Vol 12 (6) ◽

pp. 570 ◽

Cited By ~ 1

Author(s):

Roseline Mazet ◽

Josias B. G. Yaméogo ◽

Denis Wouessidjewe ◽

Luc Choisnard ◽

Annabelle Gèze

Keyword(s):

Ocular Surface ◽

Ex Vivo ◽

Immunosuppressive Agents ◽

Delivery Systems ◽

Ocular Inflammation ◽

Limiting Factors ◽

Common Symptom ◽

Eye Drops ◽

Colloidal Systems

Ocular inflammation is one of the most common symptom of eye disorders and diseases. The therapeutic management of this inflammation must be rapid and effective in order to avoid deleterious effects for the eye and the vision. Steroidal (SAID) and non-steroidal (NSAID) anti-inflammatory drugs and immunosuppressive agents have been shown to be effective in treating inflammation of the ocular surface of the eye by topical administration. However, it is well established that the anatomical and physiological ocular barriers are limiting factors for drug penetration. In addition, such drugs are generally characterized by a very low aqueous solubility, resulting in low bioavailability as only 1% to 5% of the applied drug permeates the cornea. The present review gives an updated insight on the conventional formulations used in the treatment of ocular inflammation, i.e., ointments, eye drops, solutions, suspensions, gels, and emulsions, based on the commercial products available on the US, European, and French markets. Additionally, sophisticated formulations and innovative ocular drug delivery systems will be discussed. Promising results are presented with micro- and nanoparticulated systems, or combined strategies with polymers and colloidal systems, which offer a synergy in bioavailability and sustained release. Finally, different tools allowing the physical characterization of all these delivery systems, as well as in vitro, ex vivo, and in vivo evaluations, will be considered with regards to the safety, the tolerance, and the efficiency of the drug products.

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Antimicrobial peptides expression by ocular surface cells in response to Acanthamoeba castellanii: an in vitro study

British Journal of Ophthalmology ◽

10.1136/bjo.2009.178236 ◽

2010 ◽

Vol 94 (11) ◽

pp. 1523-1527 ◽

Cited By ~ 20

Author(s):

A. M. Otri ◽

I. Mohammed ◽

A. Abedin ◽

Z. Cao ◽

A. Hopkinson ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Ocular Surface ◽

Acanthamoeba Castellanii ◽

In Vitro Study ◽

Vitro Study

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Effect of overexpression of pparγ on the healing process of corneal alkali burn in mice

AJP Cell Physiology ◽

10.1152/ajpcell.00332.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. C75-C86 ◽

Cited By ~ 46

Author(s):

Shizuya Saika ◽

Osamu Yamanaka ◽

Yuka Okada ◽

Takeshi Miyamoto ◽

Ai Kitano ◽

...

Keyword(s):

Growth Factors ◽

Ocular Surface ◽

Nuclear Translocation ◽

Healing Process ◽

Inflammatory Cells ◽

Peroxisome Proliferator ◽

Growth Factor Signaling ◽

Alkali Burn

Wound healing involves both local cells and inflammatory cells. Alkali burn of ocular surface tissue is a serious clinical problem often leading to permanent visual impairment resulting from ulceration, scarring and neovascularization during healing. Behaviors of corneal cells and inflammatory cells are orchestrated by growth factor signaling networks that have not been fully uncovered. Here we showed that adenoviral gene introduction of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits activation of ocular fibroblasts and macrophages in vitro and also induced anti-inflammatory and anti-fibrogenic responses in an alkali-burned mouse cornea. PPARγ overexpression suppressed upregulation of inflammation/scarring-related growth factors and matrix metalloproteinases (MMPs) in macrophages. It also suppressed expression of such growth factors and collagen Iα2 and myofibroblast generation upon exposure to TGFβ1. Exogenous PPARγ did not alter phosphorylation of Smad2, but inhibited its nuclear translocation. PPARγ overexpression enhanced proliferation of corneal epithelial cells, but not of fibroblasts in vitro. Epithelial cell expression of MMP-2/-9 and TGFβ1 and its migration were suppressed by PPARγ overexpression. In vivo experiments showed that PPARγ gene introduction suppressed monocytes/macrophages invasion and suppressed the generation of myofibroblasts, as well as upregulation of cytokines/growth factors and MMPs in a healing cornea. In vivo re-epitheliazation with basement membrane reconstruction in the healing, burned, cornea was accelerated by PPARγ-Ad expression, although PPARγ overexpression was considered to be unfavorable for cell migration. Together, these data suggest that overexpression of PPARγ may represent an effective new strategy for treatment of ocular surface burns.

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