Combined hyperosmolarity and inflammatory conditions in stressed human corneal epithelial cells and macrophages to evaluate osmoprotective agents as potential DED treatments

López-Cano, José Javier; González-Cela-Casamayor, Miriam Ana; Andrés‐Guerrero, Vanessa; Herrero–Vanrell, R.; Benítez-del-Castillo, J.M.; Molina‐Martínez, Irene T.

doi:10.1016/j.exer.2021.108723

Cited by 17 publications

(12 citation statements)

References 27 publications

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“…In addition, cell viability values for formulations with HPMC polymer (FLP-B and FLP-T) outperformed those without HPMC (FL-B and FL-T), with cell viability values higher than 95%. These results agree with previous research, in which HPMC has shown to have protectant activity in corneal and conjunctival cells [ 38 , 61 ]. Considering the extensive literature on the adverse effects of antiglaucomatous formulations [ 62 , 63 , 64 ], the fact that our formulations show such a high tolerance in cornea and conjunctiva cells would be a great advantage, both to reduce the side effects and to avoid the development of dry eye symptoms.…”

Section: Discussionsupporting

confidence: 93%

“…Several studies have demonstrated a significant osmoprotective and antioxidant effect in corneal epithelial cells for this aminoacid [ 24 ]. In fact, it has already demonstrated an osmoprotective activity in a hyperosmolar model in corneal cells developed by our group [ 38 ]. The osmoprotective activity of these substances were also demonstrated in this work using a hyperosmolar model in corneal cells.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro osmoprotection studies could help to select excipients and to test formulations as preliminary studies. Our group has developed an in vitro model in corneal cells capable of simulating hyperosmolar stress [ 38 ]. In this model, a 16-h exposure to a 470 mOsm/L hyperosmolar solution was used to simulate hyperosmolar stress.…”

Section: Discussionmentioning

confidence: 99%

“…Osmoprotection was performed in a previously developed hypertonic stress model in hTERT-HCECs cells [ 38 ]. This model allows the screening of osmoprotective substances or topical ophthalmic formulations in a hypertonic media.…”

Section: Methodsmentioning

confidence: 99%

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Novel Osmoprotective DOPC-DMPC Liposomes Loaded with Antihypertensive Drugs as Potential Strategy for Glaucoma Treatment

González-Cela-Casamayor

López-Cano

Bravo‐Osuna

et al. 2022

Pharmaceutics

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Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor is the elevated intraocular pressure (IOP). In this case, the treatment of choice consists of instilling antihypertensive formulations on the ocular surface. The chronicity of the pathology, together with the low bioavailability of the drugs that are applied on the ocular surface, make it necessary to instill the formulations very frequently, which is associated, in many cases, with the appearance of dry eye disease (DED). The objective of this work is the design of topical ocular formulations capable of treating glaucoma and, at the same time, preventing DED. For this, two liposome formulations, loaded with brimonidine or with travoprost, were Tadeveloped using synthetic phospholipids and enriched by the addition of compounds with osmoprotective activity. The proposed formulations not only presented physicochemical characteristics (size, pH, osmolarity, surface tension, and viscosity) and encapsulation efficiency values (EE% of 24.78% and ≥99.01% for brimonidine and travoprost, respectively) suitable for ocular surface administration, but also showed good tolerance in human corneal and conjunctival cell cultures, as well as an in vitro osmoprotective activity. The hypotensive effect of both liposomal formulations was evaluated in normotensive albino New Zealand rabbits, showing a faster and longer lasting reduction of intraocular pressure in comparison to the corresponding commercialized products used as control. According to these results, the hypotensive liposomal formulations combined with osmoprotective agents would result in a very promising platform for the treatment of glaucoma and the simultaneous protection of the ocular surface.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Novel Osmoprotective DOPC-DMPC Liposomes Loaded with Antihypertensive Drugs as Potential Strategy for Glaucoma Treatment

González-Cela-Casamayor

López-Cano

Bravo‐Osuna

et al. 2022

Pharmaceutics

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“…L-carnitine and erythritol were found in vitro to protect corneal epithelial cells from hyperosmolar stress [ 39 ]. More recently, a combination of betaine, L-carnitine and taurine demonstrated in vitro to protect epithelial cells exposed to hyperosmotic stress [ 40 ].…”

Section: Types and Roles Of Ingredients Used In Tear Substitutesmentioning

confidence: 99%

Artificial Tears: Biological Role of Their Ingredients in the Management of Dry Eye Disease

Labétoulle

Benítez-del-Castillo²,

Barabino

et al. 2022

IJMS

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Dry eye disease (DED) is the most common ocular surface disease, characterized by insufficient production and/or instability of the tear film. Tear substitutes are usually the first line of treatment for patients with DED. Despite the large variety of tear substitutes available on the market, few studies have been performed to compare their performance. There is a need to better understand the specific mechanical and pharmacological roles of each ingredient composing the different formulations. In this review, we describe the main categories of ingredients composing tear substitutes (e.g., viscosity-enhancing agents, electrolytes, osmo-protectants, antioxidants, lipids, surfactants and preservatives) as well as their effects on the ocular surface, and we provide insight into how certain components of tear substitutes may promote corneal wound healing, and/or counteract inflammation. Based on these considerations, we propose an approach to select the most appropriate tear substitute formulations according to the predominant etiological causes of DED.

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Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease

et al. 2023

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Combined hyperosmolarity and inflammatory conditions in stressed human corneal epithelial cells and macrophages to evaluate osmoprotective agents as potential DED treatments

Cited by 17 publications

References 27 publications

Novel Osmoprotective DOPC-DMPC Liposomes Loaded with Antihypertensive Drugs as Potential Strategy for Glaucoma Treatment

Novel Osmoprotective DOPC-DMPC Liposomes Loaded with Antihypertensive Drugs as Potential Strategy for Glaucoma Treatment

Artificial Tears: Biological Role of Their Ingredients in the Management of Dry Eye Disease

Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease

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