Person: Domínguez Godínez, Carmen Olalla
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First Name
Carmen Olalla
Last Name
Domínguez Godínez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Óptica y Optometría
Department
Optometría y Visión
Area
Optica
Identifiers
5 results
Search Results
Now showing 1 - 5 of 5
Item Therapeutic Targets in Dry Eye Syndrome(Drug News Perspect, 2008) Peral Cerda, María Asunción; Domínguez Godínez, Carmen Olalla; Carracedo Rodríguez, Juan Gonzalo; Pintor Just, Jesús Jerónimo; Prous ScienceDry eye is a multifactorial disease of the tears and the ocular surface that manifests with a wide variety of signs and symptoms. It is prevalent in about 33% of the population worldwide. Due to the importance of the pathology, new tests, drugs and technologies have been developed to assist the diagnosis, management and follow-up of the disease. Current available therapies try to alleviate symptoms and to reduce signs in order to restore the ocular surface. Depending on the etiology of the pathology it is possible to use lubricants, secretagogues, biological tear substitutes or antiinflammatory drugs, either independently or combined. Nowadays, the therapies under clinical trial are devoted to stimulating tear components (e.g., diquafosol, a P2Y receptor agonist), or mucin secretion (e.g., rebamipide, an amino acid analogue of quinolinone). Others include gefarnate, a water-insoluble terpene fatty acid that contributes to restoring mucins on the ocular surface, or cevimeline, an oral cholinergic agonist that reduces the symptoms associated with dry eye. Other potential compounds described in patents are in a lower phase of drug development. These compounds come from different families of therapies, and among others, can be found in the form of steroidal and nonsteroidal antiinflammatory agents, vitamins A and D, neurotransmitters and neuropeptides.Item Therapeutic potential of topical administration of siRNAs against HIF-1α for corneal neovascularization(Experimental Eye Research, 2022) Peral Cerda, María Asunción; Mateo Ibáñez, Jesús; Domínguez Godínez, Carmen Olalla; Carracedo Rodríguez, Juan Gonzalo; Gómez Pedrero, José Antonio; Crooke Álvarez, Almudena; Pintor Just, Jesús JerónimoGiven the implications of the problem of neovascularization on ocular health, as well as the growth in the number of cases, the purpose of the present study has been testing the efficacy of siRNAs (small interfering RNA) designed to silence Hypoxia Inducible Factor -1α (HIF-1α) and to demonstrate that their use stops neovascularization in a model of corneal burn. Corneal wounds in the limbic zone were made in the eyes of New Zealand white rabbits. Topical applications of siRNAs were done the next day to the wound for four consecutive days and eyes were examined with a slit lamp. Evaluation of neovascularization progress was done by analyzing images by ImageJTM and to determine the neovascular area in Matlab ® was used. At the same time, a rabbit corneal cell line was used for in vitro study of hypoxia exposure and Western blot analysis of the cell's extracts were done. Under normal cell culture oxygenation, the expression of HIF-1α was lower than that observed under hypoxic conditions. After 2 h of hypoxia, there was a significant increase in the HIF-1α expression, effect that was maintained up to 6 h. The increased in HIF-1α was mimicked by a cell permeable prolyl-4-hydroxylase inhibitor. Cobalt chloride showed no capacity to increase HIF-1α in vitro. The effect of three different siRNA on HIF-1α was tested after 4 h of hypoxia. siRNA#1 was able to silence 80% of HIF-1α expression, siRNA#2 and siRNA#3 reduce the expression in 45% and 40% respectively. In addition, the three siRNA were tested in a corneal model of neovascularization. scrambledsiRNA#2 was the most effective inhibitor of blood vessel production, followed by siRNA#3 and siRNA#1. Compared to the scrambled siRNA (100% of blood vessel generation), siRNA#2 blocked the presence of blood vessels by 83 ± 2%, siRNA#3 inhibited 45 ± 7% and siRNA#1 only inhibited 18 ± 5%. The necessary time to observe the 50% of effect showed values of NV50 of 10.2 ± 2.4 days for the scrambled siRNA, 9.1 ± 1.4 for siRNA#1, 6.5 ± 1.85 for siRNA#2 and 4.8 ± 1.8 days for siRNA#3. In conclusion, the topical application of siRNA towards HIF-1α seems to be an effective and reliable method to stop neovascularization.Item Diquafosol Delivery from Silicone Hydrogel Contact Lenses: Improved Effect on Tear Secretion(Journal of Ocular Pharmacology and Therapeutics, 2018) Domínguez Godínez, Carmen Olalla; Carracedo Rodríguez, Juan Gonzalo; Pintor Just, Jesús JerónimoPurpose: The aim of this study was to evaluate the ability to uptake and to deliver diquafosol from commercial contact lenses (CLs) and its effect on tear secretion. Methods: For both in vitro and in vivo experiments, two commercial silicone hydrogel (Si-Hy) CLs (comfilcon A and balafilcon A) were used. The CLs were soaked overnight for 12 h in diquafosol solution and control CLs were soaked in saline solution (NaCl 0.9%). The CLs were introduced into a new well container with 1 mL of saline solution, and aliquots of 100 μL were extracted at different times during a period of 6 h to measure the diquafosol release. For in vivo experiments, nine male New Zealand white rabbits were used. CLs soaked in diquafosol were inserted in the eye and compared with control CLs and diquafosol topical instillation. Schirmer's tests were performed to evaluate tear secretion and diquafosol release at different times during the 6-h period. Results: For in vitro experiments, the largest amount of diquafosol was released during the first 24 h for both CL materials under study, without statistical differences between them (P < 0.05). The topical application showed the maximum release at 1 min after instillation, meanwhile the release from both CL materials was at 30 min of insertion. The effect on tear secretion was higher with CL delivery compared with topical instillation (P < 0.05), being 300 min for both CLs and 90 min for topical application. Conclusion: The use of CLs increases the residence time of diquafosol on the ocular surface with a concomitant enhancement in tear secretion during longer periods.Item In vitro and in vivo delivery of the secretagogue diadenosine tetraphosphate from conventional and silicone hydrogel soft contact lenses(Journal of Optometry, 2013) Domínguez Godínez, Carmen Olalla; Martín Gil, Alba; Carracedo Rodríguez, Juan Gonzalo; Guzmán Aránguez, Ana Isabel; González Meijome, Jose Manuel; Pintor Just, Jesús JerónimoPurpose To evaluate the possible use of soft contact lenses (CL) to improve the secretagogue role of diadenosine tetraphosphate (Ap4A) promoting tear secretion. Methods Two conventional hydrogel CL (Omafilcon A and Ocufilcon D) and two silicone hydrogel (SiH) CL (Comfilcon A and Balafilcon A) were used. Ap4A was loaded into the lenses by soaking in a 1 mM Ap4A solution during 12 h. In vitro experiments were performed by placing the lenses in multi-wells during 2 h containing 1 ml of ultrapure water. 100 μl aliquots were taken at time zero and every minute for the first 10 min, and then every 15 min. In vivo experiments were performed in New Zealand rabbits and both the dinucleotide release from SiH and tear secretion were measured by means of Schirmer strips and high-pressure liquid chromatography (HPLC) analysis. Results Ap4A in vitro release experiments in hydrogel CL presented a release time 50 (RT50) of 3.9 ± 0.2 min and 3.1 ± 0.1 min for the non-ionic and the ionic CL, respectively. SiH CL released also Ap4A with RT50 values of 5.1 ± 0.1 min for the non-ionic and 2.7 ± 0.1 min for the ionic CL. In vivo experiments with SiH CL showed RT50 values of 9.3 ± 0.2 min and 8.5 ± 0.2 min for the non-ionic and the ionic respectively. The non-ionic lens Ap4A release was able to induce tear secretion above baseline tear levels for almost 360 min. Conclusion The delivery of Ap4A is slower and the effect lasts longer with non-ionic lenses than ionic lenses.Item Effect of Melatonin and Its Analogs on Tear Secretion(The Journal of pharmacology and experimental therapeutics, 2019) Navarro Gil, Francisco Javier; Huete Toral, Fernando; Crooke Álvarez, Almudena; Domínguez Godínez, Carmen Olalla; Carracedo Rodríguez, Juan Gonzalo; Pintor Just, Jesús JerónimoMelatonin has been shown to enhance tear secretion associated with dinucleotide diadenosine tetraphosphate. This study investigated the isolated action of melatonin and its analogs, agomelatine, N-butanoyl-2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl) ethanamine (IIK7), and 5-methoxycarbonylamino-N-cetyltryptamine (5-MCA-NAT) (10 µl at 100 µM), on tear secretion when applied topically in the rabbit cornea and its relationship with the melatonin MT1, MT2, and MT3/quinone reductase QR2 receptors. The results showed a significant increase in tear secretion, with a maximal effect at 60 minutes for the agonists (138.9% ± 6.5%, 128.9% ± 6.4%, and 120.0% ± 5.2%, respectively; P < 0.05; 100% control) but not for melatonin (101.6% ± 7.9%; P > 0.05). Agonist action was tested combined with the antagonists DH97 (MT2 selective), prazosin (MT3/QR2 inhibitor), and luzindole (nonselective MT membrane receptor) (10 µl at 100 µM). DH97 reversed the effect of agomelatine, IIK7, and 5-MCA-NAT up to 30.85% ± 7.6%,108% ± 7.2%, and 87.01% ± 7.6%, respectively (P < 0.05; 100% control). Luzindole antagonized agomelatine and 5-MCA-NAT up to 67.35% ± 7.6% and 92.12% ± 8%, respectively (P < 0.05). Prazosin only reversed 5-MCA-NAT action up to 84.2% ± 7.7% (P < 0.05). These results suggest different pathways for the agonists to act through MT membrane receptors. Therefore, agomelatine, IIK7, and 5-MCA-NAT act through MT membrane receptors as secretagogues of tear secretion, and these analogs could be considered excellent therapeutic candidates for dry eye treatment.