Person:
Crooke Álvarez, Almudena

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First Name
Almudena
Last Name
Crooke Álvarez
URI
https://hdl.handle.net/20.500.14352/79888
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Óptica y Optometría
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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2015 - 201912020 - 20221
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Author: Carracedo Rodríguez, Juan Gonzalo × Subject: 615.357 ×

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    Contact Lenses Loaded with Melatonin Analogs: A Promising Therapeutic Tool against Dry Eye Disease
    (Journal of Clinical Medicine, 2022) Navarro Gil, Francisco Javier; Huete Toral, Fernando; Domínguez Godínez, Carmen Olalla; Carracedo Rodríguez, Juan Gonzalo; Crooke Álvarez, Almudena; Versura, Piera; Dogru, Murat
    Melatonin analogs topically administered evoke a potent tear secretagogue effect in rabbits. This route of drug administration requires high drug concentration and frequent dosing due to its reduced ocular surface retention. Therefore, contact lenses (CLs) have emerged as an alternative drug- delivery system that prolongs drug retention in the cornea, improving its therapeutic performance. This study explores the in vitro ability of five commercially available hydrogel CLs to act as a delivery system for melatonin analogs and the in vivo secretagogue effect of melatonin analog-loaded CLs. We soaked CLs with melatonin or melatonin analog solutions (1 mM) for 12 h. Spectroscopic assays showed that IIK7-loaded CLs led to the inadequate delivery of this compound. Conventional hydrogel lenses loaded with agomelatine released more agomelatine than silicone ones (16–33% more). In contrast, the CLs of silicone materials are more effective as a delivery system of 5-MCA-NAT than CLs of conventional materials (24–29%). The adaptation of CLs loaded with agomelatine or 5-MCA-NAT in rabbits triggered a higher tear secretion than the corresponding eye drops (78% and 59% more, respectively). These data suggest that CLs preloaded with melatonin analogs could be an adequate strategy to combat aqueous tear deficient dry eye disease.
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    Effect of Melatonin and Analogues on Corneal Wound Healing: Involvement of Mt2 Melatonin Receptor
    (Current Eye Research, 2015) Crooke Álvarez, Almudena; Guzmán Aránguez, Ana Isabel; Mediero Muñoz, Aránzazu; Alarma Estrany, Pilar; Carracedo Rodríguez, Juan Gonzalo; Peláez García, María Teresa; Peral Cerda, María Asunción; Pintor Just, Jesús Jerónimo
    Purpose: We have investigated the effect of melatonin and its analogues on rabbit corneal epithelial wound healing. Methods: New Zealand rabbits were anaesthetised and wounds were made by placing Whatman paper discs soaked in n-heptanol on the cornea. Melatonin and analogues (all 10 nmol) were instilled. Wound diameter was measured every 2 hours by means of fluorescein application with a Topcon SL-8Z slit lamp. Melatonin antagonists (all 10 nmol) were applied 2 hours before the application of the n-heptanol-soaked disc and then every 6 hours together with melatonin. To confirm the presence of MT2 receptors in corneal epithelial cells immunohistochemistry, Western blot and RT-PCR assays in native tissue and in rabbit corneal epithelial cells were performed. The tear components were extracted then processed by HPLC to quantify melatonin in tears. Results: Migration assays revealed that melatonin and particularly the treatment with the MT2 agonist IIK7, accelerated the rate of healing (p < 0.001). The application of the non-selective melatonin receptor antagonist luzindole and the MT2 antagonist DH97 (but not prazosin), prevented the effect of melatonin on wound healing (both p < 0.001). Immunohistochemistry, Western blot and RT-PCR assays showed the presence of MT2 melatonin receptor in corneal epithelial cells. In addition, we have identified melatonin in tears and determined its daily variations. Conclusions: These data suggest that MT2 receptors are implicated in the effect of melatonin on corneal wound healing regulating migration rate. This suggests the potential use of melatonin and its analogues to enhance epithelial wound healing in ocular surface disease.