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Activation of p38 and Erk Mitogen-Activated Protein Kinases Signaling in Ocular Rosacea
Edward J Wladis1, Supraja Swamy2, Alyssa Herrmann2
1Department of Ophthalmology, Albany Medical College, Albany, New York, United States 2Department of Ophthalmology, Ophthalmic Plastic Surgery, Lions Eye Institute, Slingerlands, New York, United States.
Purpose:
Rosacea-related cutaneous inflammation is a common cause of ocular surface disease. Currently, there are no specific pharmacologic therapies to treat ocular rosacea. Here, we aimed at determining the differences in intracellular signaling activity in eyelid skin from patients with and without ocular rosacea.
Methods:
This was an observational, comparative case series including 21 patients undergoing lower lid ectropion surgery at one practice during 2013 and 2014 (18 patients with rosacea, 13 control patients), and 24 paraffin-embedded archival samples from Albany Medical Center, selected randomly (12 patients with rosacea, 12 control patients). Cutaneous biopsies resulting from elective lower lid ectropion surgery were analyzed by Proteome Profiler Human Phospho-Kinase Array, Western blot, and/or immunohistochemistry.
Results:
Samples derived from ocular rosacea patients showed increased levels of phosphorylated (active) p38 and Erk kinases. Phosphoproteins were mainly localized to the epidermis of affected eyelids.
Conclusions:
This finding provides a novel potential therapeutic target for treatment of ocular rosacea and possibly other forms of rosacea. Further testing is required to determine if p38 and Erk activation have a causal role in ocular rosacea. The selective activation of keratinocytes in the affected skin suggests that topical pathway inhibition may be an effective treatment that will ultimately prevent ocular surface damage due to ocular rosacea.
Insights
Ocular rosacea involves eyelid skin inflammation. Researchers found increased active p38 and Erk kinases in ocular rosacea patients, suggesting new therapeutic targets for this eye condition.
Area of Science:
- Dermatology
- Ophthalmology
- Molecular Biology
Background:
- Rosacea-related cutaneous inflammation frequently causes ocular surface disease.
- Current treatments for ocular rosacea lack specificity.
- Understanding intracellular signaling in eyelid skin is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate differences in intracellular signaling activity in eyelid skin between patients with and without ocular rosacea.
- To identify potential molecular targets for ocular rosacea treatment.
Main Methods:
- Observational, comparative case series involving patients undergoing lower lid ectropion surgery.
- Analysis of cutaneous biopsies using Proteome Profiler Human Phospho-Kinase Array, Western blot, and immunohistochemistry.
- Inclusion of both fresh surgical samples and archival paraffin-embedded tissues.
Main Results:
- Elevated levels of phosphorylated (active) p38 and Erk kinases were observed in samples from ocular rosacea patients.
- These phosphoproteins were predominantly localized to the epidermis of affected eyelids.
- Kinase activation suggests a specific cellular response in rosacea-affected skin.
Conclusions:
- Increased p38 and Erk kinase activity presents a novel potential therapeutic target for ocular rosacea.
- Further research is needed to confirm the causal role of p38 and Erk activation in ocular rosacea.
- Targeting these pathways topically may offer an effective treatment to prevent ocular surface damage.
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