Publications by authors named "Mireya Martinez"

5 Publications

  • Page 1 of 1

HIF-1α and HIF-2α redundantly promote retinal neovascularization in patients with ischemic retinal disease.

J Clin Invest 2021 Jun;131(12)

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Therapies targeting VEGF have proven only modestly effective for the treatment of proliferative sickle cell retinopathy (PSR), the leading cause of blindness in patients with sickle cell disease. Here, we shift our attention upstream from the genes that promote retinal neovascularization (NV) to the transcription factors that regulate their expression. We demonstrated increased expression of HIF-1α and HIF-2α in the ischemic inner retina of PSR eyes. Although both HIFs participated in promoting VEGF expression by hypoxic retinal Müller cells, HIF-1 alone was sufficient to promote retinal NV in mice, suggesting that therapies targeting only HIF-2 would not be adequate to prevent PSR. Nonetheless, administration of a HIF-2-specific inhibitor currently in clinical trials (PT2385) inhibited NV in the oxygen-induced retinopathy (OIR) mouse model. To unravel these discordant observations, we examined the expression of HIFs in OIR mice and demonstrated rapid but transient accumulation of HIF-1α but delayed and sustained accumulation of HIF-2α; simultaneous expression of HIF-1α and HIF-2α was not observed. Staggered HIF expression was corroborated in hypoxic adult mouse retinal explants but not in human retinal organoids, suggesting that this phenomenon may be unique to mice. Using pharmacological inhibition or an in vivo nanoparticle-mediated RNAi approach, we demonstrated that inhibiting either HIF was effective for preventing NV in OIR mice. Collectively, these results explain why inhibition of either HIF-1α or HIF-2α is equally effective for preventing retinal NV in mice but suggest that therapies targeting both HIFs will be necessary to prevent NV in patients with PSR.
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June 2021

Microscopic Study of Injectable Steroids: Effects of Postmixing Time on Particle Aggregation.

Pain Physician 2020 07;23(4):E417-E424

Department of Pathology, University of Valencia, Spain.

Background: Epidural steroid injection (ESI) is a common practice for pain treatment since 1953. In 2014, the FDA issued a warning about ESI. Studies have focused on the effect of the particle size and their ability to generate harmful aggregates. Although steroid aggregates provide longer times for reabsorption, therefore a longer anti-inflammatory effect, they are potentially harmful to the central nervous system via embolic mechanisms.Previous studies have established that steroidal aggregates with asizes over 100 mu m are potentially able to occlude blood vessels. Studies by Tiso et al and Benzon et al addressed the role of steroids on CNS adverse events, with similar outcomes. The main difference was on the role of aggregates with a size over 100 mu m, which Benzon et al. attributed to the ability of certain steroid preparations to rapidly precipitate and form large aggregates.

Objectives: Studying the effect of the time elapsed between mixing the steroid preparation and injection on the number and size of aggregates with sizes above 100 mu m.

Study Design: Original study in basic science.

Setting: Basic scienceMETHODS: Steroids evaluated are commonly used in Spain for ESI: betamethasone, triamcinolone, and dexamethasone. The size and number of the aggregates was determined for undiluted commercial steroid preparations in the usual amount for a single and double dosage used for ESI.Samples were examined with a Leica TCS-SP2 microscope at the first, the fifth and the 30th minute after shaking the preparations. Aggregates observed in the different preparations were manually counted and grouped in the following size range: 0-20, 20-50, 50-100, 100-300, 300-500 and > 500 mu m.Statistical analysis was carried out using the R software. Nonparametric techniques were used in the comparison of aggregate size. Global comparison of the groups using the Kruskal-Wallis test and post-hoc comparisons using the Wilcoxon test, adjusting P-values by the Holm method for multiple comparisonsRESULTS: Aggregates present in triamcinolone and betamethasone samples were statistically larger than in dexamethasone samples. Triamcinolone suspensions produced significantly larger aggregates than betamethasone five minutes after mixing. Triamcinolone preparations produced greater particle aggregates (> 500 mu m), which were not present in dexamethasone and betamethasone preparations.

Limitations: Study how the human internal factors like blood elements and spinal fluid could interact with steroids and influence the size of the aggregates formed.

Conclusions: This study demonstrates that the size of the particles injected depends on the type of steroid and the time allowed between mixing and injecting. The results demonstrate that waiting longer than 5 minutes between mixing and injecting can predispose the formation of potentially harmful aggregates in triamcinolone and betamethasone samples. The presence of greater particle aggregates (> 500 mu m) may occlude some important vessels and arteries with serious adverse results. Vigorous shaking of the injectable could prevent such events.

Key Words: Epidural steroid injection, triamcinolone, betamethasone, dexamethasone, steroid aggregates.
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July 2020

Optical Coherence Tomography in Patients with Chronic Migraine: Literature Review and Update.

Front Neurol 2017 13;8:684. Epub 2017 Dec 13.

Department of Ophthalmology, Poznan City Hospital, Poznan, Poland.

Migraine is a chronic disease characterized by unilateral, pulsating, and often moderate-to-severe recurrent episodes of headache with nausea and vomiting. It affects approximately 15% of the general population, yet the underlying pathophysiological mechanisms are not fully understood. Optical coherence tomography (OCT) is a safe and reproducible diagnostic technique that utilizes infrared wavelengths and has a sensitivity of 8-10 μm. It can be used to measure thinning of the retinal nerve fiber layer (RNFL) in some neurological disorders. Although ophthalmologists are often the first specialists to examine patients with migraine, few studies have addressed the involvement of the optic nerve and retino-choroidal structures in this group. We reviewed the literature on the etiological and pathological mechanisms of migraine and the relationship between recurrent constriction of cerebral and retrobulbar vessels and ischemic damage to the optic nerve, retina, and choroid. We also assessed the role of OCT for measuring peripapillary RNFL thickness and macular and choroidal changes in migraine patients. There is considerable evidence of cerebral and retrobulbar vascular involvement in the etiology of migraine. Transitory and recurrent constriction of the retinal and ciliary arteries may cause ischemic damage to the optic nerve, retina, and choroid in patients with migraine. OCT to assess the thickness of the peripapillary RNFL, macula, and choroid might increase our understanding of the pathophysiology of migraine and facilitate diagnosis of retino-choroidal compromise and follow-up of therapy in migraine patients. Future studies should determine the usefulness of OCT findings as a biomarker of migraine.
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December 2017

The Contribution of Optical Coherence Tomography in Neuromyelitis Optica Spectrum Disorders.

Front Neurol 2017 29;8:493. Epub 2017 Sep 29.

Department of Ophthalmology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.

Neuromyelitis optica spectrum disorders (NMOSD) comprises a group of central nervous system disorders of inflammatory autoimmune origin that mainly affect the optic nerves and the spinal cord and can cause severe visual and general disability. The clinical signs are similar to those of multiple sclerosis (MS), with the result that it is often difficult to differentiate between the two, thus leading to misdiagnosis. As the treatment and prognosis of NMOSD and MS are different, it is important to make an accurate and early diagnosis of NMOSD. Optical coherence tomography (OCT) is a non-invasive technique that enables a quantitative study of the changes that the optic nerve and the macula undergo in several neurodegenerative diseases. Many studies have shown that some of these changes, such as retinal nerve fiber layer thinning or microcystic macular edema, can be related to alterations in the brain due to neurodegenerative disorders. The purpose of this mini-review is to show how OCT can be useful for the diagnosis of NMOSD and follow-up of affected patients, as well as for the differential diagnosis with MS.
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September 2017

Vibrational and electronic spectra of 9,10-dihydrobenzo(a)pyren-7(8H)-one and 7,8,9,10-tetrahydrobenzo(a)pyrene: an experimental and computational study.

Spectrochim Acta A Mol Biomol Spectrosc 2011 Oct 17;81(1):162-71. Epub 2011 Jun 17.

Department of Chemistry, Stephen F. Austin State University, Box 3006-SFA Station, Nacogdoches, TX 75962-3006, USA.

The molecular geometries, vibrational and UV-vis spectra of 9,10-dihydrobenzo(a)pyrene-7(8H)-one (9,10-H(2)BaP) and 7,8,9,10-tetrahydrobenzo(a)pyrene (7,8,9,10-H(4)BaP) were investigated using density functional theory (DFT-B3LYP), with the triple-ζ 6-311+G(d,p) and Dunning's cc-pVTZ basis sets. From the comparison of infrared experimental and calculated infrared, and Raman data comprehensive assignments are made. The calculated infrared frequencies below 1800 cm(-1) are in good agreement with experimental data, with an average deviation of <4 cm(-1). Using the B3LYP/6-311+G(d,p)//TD-B3LYP/6-311G(d,p) level of theory, transition energies, and oscillator strengths of the 30 lowest electronic absorption bands are assigned to π-π* transitions, with good qualitative agreement between experimental and simulated absorption data. In addition, the HOMO-LUMO gaps and their chemical hardness were analyzed.
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October 2011