Person:
López Cuenca, Inés

First Name

Inés

Last Name

López Cuenca

URI

https://hdl.handle.net/20.500.14352/85492

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Medicina

Department

Inmunología, Oftalmología y ORL

Identifiers

Full item page

Search Results

Now showing 1 - 10 of 12

Macular Thickness Decrease in Asymptomatic Subjects at High Genetic Risk of Developing Alzheimer’s Disease: An OCT Study
(Journal of Clinical Medicine, 2020) López Cuenca, Inés; Hoz Montañana, María Rosa De; García Martín, Elena Salobrar; Elvira Hurtado, Lorena; Rojas Lozano, María Del Pilar; Fernández Albarral, José Antonio; Barabash Bustelo, Ana; Salazar Corral, Juan José; Ramírez Sebastián, Ana Isabel; Ramírez Sebastián, José Manuel
In this case control study, we examined the retinal thickness of the different layers in the macular region and peripapillary retinal nerve fiber layer (RNFL) with optical coherence tomography (OCT) in healthy cognitive subjects (from 51 to 74 years old) at high genetic risk for developing Alzheimer’s disease (AD). Thirty-five subjects with a family history of Alzheimer disease (AD) (FH+) and ApoE ɛ4 carriers and 29 age-matched control subjects without a family history of AD (FH−) and ApoE ɛ4 non-carriers were included. Compared to FH− ApoE ɛ4 non-carriers, in FH+ ApoE ɛ4 carriers, there were statistically significant decreases (p < 0.05) in (i) the foveal area of mRNFL; (ii) the inferior and nasal sectors in the outer and inner macular ring in the inner plexiform layer (IPL); (iii) the foveal area and the inferior sector in the outer macular ring in the inner nuclear layer (INL); and (iv) the inferior sector of the outer macular ring in the outer plexiform layer (OPL). However, no statistically significant differences were found in the peripapillary thickness of RNFL between both study groups. In subjects with cognitive health and high genetic risk for the development of AD, initial changes appeared in the macular area. OCT could be a promising, cost-effective and non-invasive test useful in early AD, before the onset of clinical symptoms.
The Value of OCT and OCTA as Potential Biomarkers for Preclinical Alzheimer's Disease: A Review Study
(Life, 2021) López Cuenca, Inés; García Martín, Elena Salobrar; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Sánchez-Puebla Fernández, Lidia; Salazar Corral, Juan José; Ramírez Sebastián, José Manuel; Ramírez Sebastián, Ana Isabel; Hoz Montañana, María Rosa De
Preclinical Alzheimer’s disease (AD) includes cognitively healthy subjects with at least one positive biomarker: reduction in cerebrospinal fluid Aβ42 or visualization of cerebral amyloidosis by positron emission tomography imaging. The use of these biomarkers is expensive, invasive, and not always possible. It has been shown that the retinal changes measured by optical coherence tomography (OCT) and OCT-angiography (OCTA) could be biomarkers of AD. Diagnosis in early stages before irreversible AD neurological damage takes place is important for the development of new therapeutic interventions. In this review, we summarize the findings of different published studies using OCT and OCTA in participants with preclinical AD. To date, there have been few studies on this topic and they are methodologically very dissimilar. Moreover, these include only two longitudinal studies. For these reasons, it would be interesting to unify the methodology, make the inclusion criteria more rigorous, and conduct longer longitudinal studies to assess the evolution of these subjects. If the results were consistent across repeated studies with the same methodology, this could provide us with insight into the value of the retinal changes observed by OCT/OCTA as potential reliable, cost-effective, and noninvasive biomarkers of preclinical AD.
Foveal Avascular Zone and Choroidal Thickness Are Decreased in Subjects with Hard Drusen and without High Genetic Risk of Developing Alzheimer’s Disease
(Biomedicines, 2021) López Cuenca, Inés; Hoz Montañana, María Rosa De; Alcántara Rey, Celia; García Martín, Elena Salobrar; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Barabash Bustelo, Ana; Ramírez Toraño, Federico; De Frutos Lucas, Jaisalmer; Salazar Corral, Juan José; Ramírez Sebastián, Ana Isabel; Ramírez Sebastián, José Manuel
A family history (FH+) of Alzheimer’s disease (AD) and ε4 allele of the ApoE gene are the main genetic risk factors for developing AD, whereas ε4 allele plays a protective role in age-related macular degeneration. Ocular vascular changes have been reported in both pathologies. We analyzed the choroidal thickness using optical coherence tomography (OCT) and the foveal avascular zone (FAZ) using OCT-angiography and compared the results with ApoE gene expression, AD FH+, and the presence or absence of hard drusen (HD) in 184 cognitively healthy subjects. Choroidal thickness was statistically significantly different in the (FH−, ε4−, HD+) group compared with (i) both the (FH−, ε4−, HD−) and the (FH+, ε4+, HD+) groups in the superior and inferior points at 1500 µm, and (ii) the (FH+, ε4−, HD+) group in the superior point at 1500 µm. There were statistically significant differences in the superficial FAZ between the (FH+, ε4−, HD+) group and (i) the (FH+, ε4−, HD−) group and (ii) the (FH+, ε4+, HD−) group. In conclusion, ocular vascular changes are not yet evident in participants with a genetic risk of developing AD.
Microglial Activation in the Retina of a Triple-Transgenic Alzheimer’s Disease Mouse Model (3xTg-AD)
(International Journal of Molecular Sciences, 2020) García Martín, Elena Salobrar; Rodríguez Neves, Ana C.; Ramírez Sebastián, Ana Isabel; Hoz Montañana, María Rosa De; Fernández Albarral, José Antonio; López Cuenca, Inés; Ramírez Sebastián, José Manuel; Ambrosio, Antonio Francisco; Salazar Corral, Juan José
Alzheimer’s disease (AD) is the most common type of dementia in the world. The main biomarkers associated with AD are protein amyloid-β (Aβ) plaques and protein tau neurofibrillary tangles, which are responsible for brain neuroinflammation mediated by microglial cells. Increasing evidence has shown that the retina can also be affected in AD, presenting some molecular and cellular changes in the brain, such as microglia activation. However, there are only a few studies assessing such changes in the retinal microglia in animal models of AD. These studies use retinal sections, which have some limitations. In this study, we performed, for the first time in a triple-transgenic AD mouse model (3xTg-AD), a quantitative morphometric analysis of microglia activation (using the anti-Iba-1 antibody) in retinal whole-mounts, allowing visualization of the entire microglial cell, as well as its localization along the extension of the retina in different layers. Compared to age-matched animals, the retina of 3xTg-AD mice presents a higher number of microglial cells and a thicker microglial cell body area. Moreover, the microglia migrate, reorient, and retract their processes, changing their localization from a parallel to a perpendicular position relative to the retinal surface. These findings demonstrate clear microglia remodeling in the retina of 3xTg-AD mice.
Characterization of Retinal Drusen in Subjects at High Genetic Risk of Developing Sporadic Alzheimer’s Disease: An Exploratory Analysis
(Journal of Personalized Medicine, 2022) López Cuenca, Inés; García Martín, Elena Salobrar; Gil Salgado, Inés; Sánchez-Puebla Fernández, Lidia; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Ramírez Toraño, Federico; Barabash Bustelo, Ana; De Frutos Lucas, Jaisalmer; Salazar Corral, Juan José; Ramírez Sebastián, José Manuel; Ramírez Sebastián, Ana Isabel; Hoz Montañana, María Rosa De
Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ɛ4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH- or FH+) and their allelic characterization of ApoE ɛ4 (ApoE ɛ4- or ApoE ɛ4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate drusen
Exploratory Longitudinal Study of Ocular Structural and Visual Functional Changes in Subjects at High Genetic Risk of Developing Alzheimer’s Disease
(Biomedicines, 2023) López Cuenca, Inés; García Martín, Elena Salobrar; Barabash Bustelo, Ana; Nebreda Pérez, Alberto; Ramírez Toraño, Federico; Sánchez Puebla, Lidia; García Colomo, Alejandra; Fernández Albarral, José; Ramírez Sebastián, Ana Isabel; Ramírez Sebastián, José Manuel; Maestu Unturbe, Fernando; Salazar Corral, Juan José; Gil Gregorio, Pedro; Álvarez Gutierrez, María; Elvira Hurtado, Lorena; Matamoros, José A.; Hoz Montañana, María Rosa De
This study aimed to analyze the evolution of visual changes in cognitively healthy individuals at risk for Alzheimer’s disease (AD). Participants with a first-degree family history of AD (FH+) and carrying the Ε4+ allele for the ApoE gene (ApoE ε4+) underwent retinal thickness analysis using optical coherence tomography (OCT) and visual function assessments, including visual acuity (VA), contrast sensitivity (CS), color perception, perception digital tests, and visual field analysis. Structural analysis divided participants into FH+ ApoE ε4+ and FH− ApoE ε4− groups, while functional analysis further categorized them by age (40–60 years and over 60 years). Over the 27-month follow-up, the FH+ ApoE ε4+ group exhibited thickness changes in all inner retinal layers. Comparing this group to the FH− ApoE ε4− group at 27 months revealed progressing changes in the inner nuclear layer. In the FH+ ApoE ε4+ 40–60 years group, no progression of visual function changes was observed, but an increase in VA and CS was maintained at 3 and 12 cycles per degree, respectively, compared to the group without AD risk at 27 months. In conclusion, cognitively healthy individuals at risk for AD demonstrated progressive retinal structural changes over the 27-month follow-up, while functional changes remained stable.
OCT Imaging in Murine Models of Alzheimer’s Disease in a Systematic Review: Findings, Methodology and Future Perspectives
(Biomedicines, 2024) Sánchez-Puebla Fernández, Lidia; López Cuenca, Inés; García Martín, Elena Salobrar; Fernández Albarral, José; Matamoros Felipe, José Antonio; Elvira Hurtado, Lorena; Salazar Corral, Juan José; Ramírez Sebastián, José Manuel; Hoz Montañana, María Rosa De; Ramírez Sebastián, Ana Isabel
The murine models of Alzheimer’s disease (AD) have advanced our understanding of the pathophysiology. In vivo studies of the retina using optical coherence tomography (OCT) have complemented histological methods; however, the lack of standardisation in OCT methodologies for murine models of AD has led to significant variations in the results of different studies. A literature search in PubMed and Scopus has been performed to review the different methods used in these models using OCT and to analyse the methodological characteristics of each study. In addition, some recommendations are offered to overcome the challenges of using OCT in murine models. The results reveal a lack of consensus on OCT device use, retinal area analysed, segmentation techniques, and analysis software. Although some studies use the same OCT device, variations in other parameters make the direct comparison of results difficult. Standardisation of retinal analysis criteria in murine models of AD using OCT is crucial to ensure consistent and comparable results. This implies the application of uniform measurement and segmentation protocols. Despite the absence of standardisation, OCT has proven valuable in advancing our understanding of the pathophysiology of AD.
Alzheimer’s disease: a continuum with visual involvements
(Frontiers in psychology, 2023) Elvira Hurtado, Lorena; López Cuenca, Inés; Hoz Montañana, María Rosa De; Salas, Mario; Sánchez-Puebla Fernández, Lidia; Ramírez Toraño, Federico; Matamoros, José Antonio; Fernández Albarral, José; Rojas Lozano, María Del Pilar; Alfonsín, Soraya; Delgado Losada, María Luisa; Ramírez, Ana I.; Salazar Corral, Juan José; Maestu Unturbe, Fernando; Gil Gregorio, Pedro; Ramírez Sebastián, José Manuel; García Martín, Elena Salobrar
Introduction: Alzheimer’s disease (AD) is the most common form of dementia affecting the central nervous system, and alteration of several visual structures has been reported. Structural retinal changes are usually accompanied by changes in visual function in this disease. The aim of this study was to analyse the differences in visual function at different stages of the pathology (family history group (FH+), mild cognitive impairment (MCI), mild AD and moderate AD) in comparison with a control group of subjects with no cognitive decline and no family history of AD. Methods: We included 53 controls, 13 subjects with FH+, 23 patients with MCI, 25 patients with mild AD and, 21 patients with moderate AD. All were ophthalmologically healthy. Visual acuity (VA), contrast sensitivity (CS), colour perception, visual integration, and fundus examination were performed. Results: The analysis showed a statistically significant decrease in VA, CS and visual integration score between the MCI, mild AD and moderate AD groups compared to the control group. In the CS higher frequencies and in the colour perception test (total errors number), statistically significant differences were also observed in the MCI, mild AD and moderate AD groups with respect to the FH+ group and also between the control and AD groups. The FH+ group showed no statistically significant difference in visual functions compared to the control group. All the test correlated with the Mini Mental State Examination score and showed good predictive value when memory decline was present, with better values when AD was at a more advanced stage. Conclusion: Alterations in visual function appear in subjects with MCI and evolve when AD is established, being stable in the initial stages of the disease (mild AD and moderate AD). Therefore, visual psychophysical tests are a useful, simple and complementary tool to neuropsychological tests to facilitate diagnosis in the preclinical and early stages of AD.
The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma
(Frontiers in Aging Neuroscience, 2017) Ramírez Sebastián, Ana Isabel; Hoz Montañana, María Rosa De; García Martín, Elena Salobrar; Salazar Corral, Juan José; Rojas López, María Blanca; Ajoy, Daniel; López Cuenca, Inés; Rojas Lozano, María Del Pilar; Triviño Casado, Alberto; Ramírez Sebastián, José Manuel
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions. The retina is an extension of the brain and therefore the inflammatory response in the brain can occur in the retina. The brain and retina are affected in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and glaucoma. AD is an age-related neurodegeneration of the CNS characterized by neuronal and synaptic loss in the cerebral cortex, resulting in cognitive deficit and dementia. The extracellular deposits of beta-amyloid (Aβ) and intraneuronal accumulations of hyperphosphorylated tau protein (pTau) are the hallmarks of this disease. These deposits are also found in the retina and optic nerve. PD is a neurodegenerative locomotor disorder with the progressive loss of dopaminergic neurons in the substantia nigra. This is accompanied by Lewy body inclusion composed of α-synuclein (α-syn) aggregates. PD also involves retinal dopaminergic cell degeneration. Glaucoma is a multifactorial neurodegenerative disease of the optic nerve, characterized by retinal ganglion cell loss. In this pathology, deposition of Aβ, synuclein, and pTau has also been detected in retina. These neurodegenerative diseases share a common pathogenic mechanism, the neuroinflammation, in which microglia play an important role. Microglial activation has been reported in AD, PD, and glaucoma in relation to protein aggregates and degenerated neurons. The activated microglia can release pro-inflammatory cytokines which can aggravate and propagate neuroinflammation, thereby degenerating neurons and impairing brain as well as retinal function. The aim of the present review is to describe the contribution in retina to microglial-mediated neuroinflammation in AD, PD, and glaucomatous neurodegeneration.
The relationship between retinal layers and brain areas in asymptomatic first-degree relatives of sporadic forms of Alzheimer’s disease: an exploratory analysis
(Alzheimer's Research & Therapy, 2022) López Cuenca, Inés; Marcos Dolado, Alberto; Yus Fuertes, Miguel; García Martín, Elena Salobrar; Elvira Hurtado, Lorena; Fernández Albarral, José Antonio; Salazar Corral, Juan José; Ramírez Sebastián, Ana Isabel; Sánchez-Puebla Fernández, Lidia; Fuentes Ferrer, Manuel Enrique; Barabash Bustelo, Ana; Ramírez Toraño, Federico; Gil Martínez, Lidia; Arrazola García, Juan Lorenzo; Gil Gregorio, Pedro; Hoz Montañana, María Rosa De; Ramírez Sebastián, José Manuel
Background: Two main genetic risks for sporadic Alzheimer’s disease (AD) are a family history and ɛ4 allele of apolipoprotein E. The brain and retina are part of the central nervous system and share pathophysiological mechanisms in AD. Methods: We performed a cross-sectional study with 30 participants without a family history of sporadic AD (FH−) and noncarriers of ApoE ɛ4 (ApoE ɛ4−) as a control group and 34 participants with a family history of sporadic AD (FH+) and carriers of at least one ɛ4 allele (ApoE ɛ4+). We analyzed the correlations between macular volumes of retinal layers and thickness of the peripapillary retinal nerve fiber layer (pRNFL) measured by optical coherence tomography (OCT) with the brain area parameters measured by magnetic resonance imaging (MRI) in participants at high genetic risk of developing AD (FH+ ApoE ɛ4+). Results: We observed a significant volume reduction in the FH+ ApoE ɛ4+ group compared with the control group in some macular areas of (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL), (iii) inner nuclear layer (INL), and (iv) outer plexiform layer (OPL). Furthermore, in the FH+ ApoE ɛ4+ group, the retinal sectors that showed statistically significant volume decrease correlated with brain areas that are affected in the early stages of AD. In the same group, the peripapillary retinal nerve fiber layer (pRNFL) did not show statistically significant changes in thickness compared with the control group. However, correlations of these sectors with the brain areas involved in this disease were also found. Conclusions: In cognitively healthy participants at high genetic risk of developing sporadic forms of AD, there are significant correlations between retinal changes and brain areas closely related to AD such as the entorhinal cortex, the lingual gyrus, and the hippocampus.