DigitalUM :: Browsing by browse.metadata.contributordepartment "Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica"

Browsing by browse.metadata.contributordepartment "Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica"

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Open Access
7,8-Dihydroxiflavone maintains retinal functionality and protects various types of RGCs in adult rats with optic nerve transection
(MDPI, 2021-10-30) Gallego Ortega, Alejandro; Vidal Villegas, Beatriz; Norte Muñoz, María; Salinas Navarro, Manuel Ángel; Avilés Trigueros, Marcelino; Villegas Pérez, Maria Paz; Vidal Sanz, Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
To analyze the neuroprotective effects of 7,8-Dihydroxyflavone (DHF) in vivo and ex vivo, adult albino Sprague-Dawley rats were given a left intraorbital optic nerve transection (IONT) and were divided in two groups: One was treated daily with intraperitoneal (ip) DHF (5 mg/kg) (n = 24) and the other (n = 18) received ip vehicle (1% DMSO in 0.9% NaCl) from one day before IONT until processing. At 5, 7, 10, 12, 14, and 21 days (d) after IONT, full field electroretinograms (ERG) were recorded from both experimental and one additional naïve-control group (n = 6). Treated rats were analyzed 7 (n = 14), 14 (n = 14) or 21 d (n = 14) after IONT, and the retinas immune stained against Brn3a, Osteopontin (OPN) and the T-box transcription factor T-brain 2 (Tbr2) to identify surviving retinal ganglion cells (RGCs) (Brn3a+), α-like (OPN+), α-OFF like (OPN+Brn3a+) or M4-like/α-ON sustained RGCs (OPN+Tbr+). Naïve and right treated retinas showed normal ERG recordings. Left vehicle-treated retinas showed decreased amplitudes of the scotopic threshold response (pSTR) (as early as 5 d), the rod b-wave, the mixed response and the cone response (as early as 10 d), which did not recover with time. In these retinas, by day 7 the total numbers of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs decreased to less than one half and OPN+Brn3a+RGCs decreased to approximately 0.5%, and Brn3a+RGCs showed a progressive loss with time, while OPN+RGCs and OPN+Tbr2+RGCs did not diminish after seven days. Compared to vehicle-treated, the left DHF-treated retinas showed significantly greater amplitudes of the pSTR, normal b-wave values and significantly greater numbers of OPN+RGCs and OPN+Tbr2+RGCs for up to 14 d and of Brn3a+RGCs for up to 21 days. DHF affords significant rescue of Brn3a+RGCs, OPN+RGCs and OPN+Tbr2+RGCs, but not OPN+Brn3a+RGCs, and preserves functional ERG responses after IONT.
Open Access
7,8-Dihydroxiflavone protects adult rat axotomized retinal ganglion cells through MAPK/ERK and PI3K/AKT activation
(MDPI, 2021-10-08) Galindo Romero, Caridad; Vidal-Villegas, Beatriz; Asís-Martínez, Javier; Lucas Ruiz, Fernando; Gallego Ortega, Alejandro; Vidal Sanz, Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Óptica y Optometría
We analyze the 7,8-dihydroxyflavone (DHF)/TrkB signaling activation of two main intracellular pathways, mitogen-activated protein kinase (MAPK)/ERK and phosphatidylinositol 3 kinase (PI3K)/AKT, in the neuroprotection of axotomized retinal ganglion cells (RGCs). Methods: Adult albino Sprague-Dawley rats received left intraorbital optic nerve transection (IONT) and were divided in two groups. One group received daily intraperitoneal DHF (5 mg/kg) and another vehicle (1%DMSO in 0.9%NaCl) from one day before IONT until processing. Additional intact rats were employed as control (n = 4). At 1, 3 or 7 days (d) after IONT, phosphorylated (p)AKT, p-MAPK, and non-phosphorylated AKT and MAPK expression levels were analyzed in the retina by Western blotting (n = 4/group). Radial sections were also immunodetected for the above-mentioned proteins, and for Brn3a and vimentin to identify RGCs and Müller cells (MCs), respectively (n = 3/group). Results: IONT induced increased levels of p-MAPK and MAPK at 3d in DHF- or vehicle-treated retinas and at 7d in DHF-treated retinas. IONT induced a fast decrease in AKT in retinas treated with DHF or vehicle, with higher levels of phosphorylation in DHF-treated retinas at 7d. In intact retinas and vehicle-treated groups, no p-MAPK or MAPK expression in RGCs was observed. In DHF- treated retinas p-MAPK and MAPK were expressed in the ganglion cell layer and in the RGC nuclei 3 and 7d after IONT. AKT was observed in intact and axotomized RGCs, but the signal intensity of p-AKT was stronger in DHF-treated retinas. Finally, MCs expressed higher quantities of both MAPK and AKT at 3d in both DHF- and vehicle-treated retinas, and at 7d the phosphorylation of p-MAPK was higher in DHF-treated groups. Conclusions: Phosphorylation and increased levels of AKT and MAPK through MCs and RGCs in retinas after DHF-treatment may be responsible for the increased and long-lasting RGC protection afforded by DHF after IONT.
Open Access
A high-density narrow-field inhibitory retinal interneuron with direct coupling to Müller glia
(Society for Neuroscience, 2021-07-14) Grimes, William N. ; Aytürk, Didem Göz ; Hoon, Mrinalini ; Yoshimatsu, Takeshi ; Gamlin, Clare ; Carrera, Daniel ; Nath, Amurta ; Ahlquist, Richard M. ; Sabnis, Adit ; Berson, David M. ; Diamond, Jeffrey S. ; Wong, Rachel O. ; Cepko, Connie ; Rieke, Fred ; Nadal-Nicolás, Francisco Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Medicina
Amacrine cells are interneurons composing the most diverse cell class in the mammalian retina. They help encode visual features, such as edges or directed motion, by mediating excitatory and inhibitory interactions between input (i.e., bipolar) and output (i.e., ganglion) neurons in the inner plexiform layer (IPL). Like other brain regions, the retina also contains glial cells that contribute to neurotransmitter uptake, metabolic regulation, and neurovascular control. Here, we report that, in mouse retina (of either sex), an abundant, though previously unstudied inhibitory amacrine cell is coupled directly to Müller glia. Electron microscopic reconstructions of this amacrine type revealed chemical synapses with known retinal cell types and extensive associations with Müller glia, the processes of which often completely ensheathe the neurites of this amacrine cell. Microinjecting small tracer molecules into the somas of these amacrine cells led to selective labeling of nearby Müller glia, leading us to suggest the name "Müller glia-coupled amacrine cell," or MAC. Our data also indicate that MACs release glycine at conventional chemical synapses, and viral retrograde transsynaptic tracing from the dorsal lateral geniculate nucleus showed selective connections between MACs and a subpopulation of retinal ganglion cell types. Visually evoked responses revealed a strong preference for light increments; these "ON" responses were primarily mediated by excitatory chemical synaptic input and direct electrical coupling with other cells. This initial characterization of the MAC provides the first evidence for neuron-glia coupling in the mammalian retina and identifies the MAC as a potential link between inhibitory processing and glial function. SIGNIFICANCE STATEMENT Gap junctions between pairs of neurons or glial cells are commonly found throughout the nervous system and play multiple roles, including electrical coupling and metabolic exchange. In contrast, gap junctions between neurons and glia cells have rarely been reported and are poorly understood. Here we report the first evidence for neuron-glia coupling in the mammalian retina, specifically between an abundant (but previously unstudied) inhibitory interneuron and Müller glia. Moreover, viral tracing, optogenetics, and serial electron microscopy provide new information about the neuron's synaptic partners and physiological responses.
Open Access
A novel in vivo model of focal light emitting diode-induced cone-photoreceptor phototoxicity: neuroprotection afforded by brimonidine, BDNF, PEDF or bFGF
(Public Library of Science , 2014-12-02) Ortín Martínez, Arturo; Valiente Soriano, Francisco Javier; García Ayuso, Diego; Jiménez López, Manuel; Bernal Garro, José Manuel; Nieto López, Leticia; Nadal-Nicolás, Francisco Manuel; Villegas Pérez, Maria Paz; Wheeler, Larry A.; Vidal Sanz, Manuel; Alarcón Martínez, Luis; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
We have investigated the effects of light-emitting diode (LED)-induced phototoxicity (LIP) on cone-photoreceptors and their protection with brimonidine (BMD), brain-derived neurotrophic factor (BDNF), pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF) or basic fibroblast growth factor (bFGF). In anesthetized, dark adapted, adult albino rats a blue (400 nm) LED was placed perpendicular to the cornea (10 sec, 200 lux) and the effects were investigated using Spectral Domain Optical Coherence Tomography (SD-OCT) and/or analysing the retina in oriented cross-sections or wholemounts immune-labelled for L- and S-opsin and counterstained with the nuclear stain DAPI. The effects of topical BMD (1%) or, intravitreally injected BDNF (5 µg), PEDF (2 µg), CNTF (0.4 µg) or bFGF (1 µg) after LIP were examined on wholemounts at 7 days. SD-OCT showed damage in a circular region of the superotemporal retina, whose diameter varied from 1,842.4±84.5 µm (at 24 hours) to 1,407.7±52.8 µm (at 7 days). This region had a progressive thickness diminution from 183.4±5 µm (at 12 h) to 114.6±6 µm (at 7 d). Oriented cross-sections showed within the light-damaged region of the retina massive loss of rods and cone-photoreceptors. Wholemounts documented a circular region containing lower numbers of L- and S-cones. Within a circular area (1 mm or 1.3 mm radius, respectively) in the left and in its corresponding region of the contralateral-fellow-retina, total L- or S-cones were 7,118±842 or 661±125 for the LED exposed retinas (n = 7) and 14,040±1,860 or 2,255±193 for the fellow retinas (n = 7), respectively. BMD, BDNF, PEDF and bFGF but not CNTF showed significant neuroprotective effects on L- or S-cones. We conclude that LIP results in rod and cone-photoreceptor loss, and is a reliable, quantifiable model to study cone-photoreceptor degeneration. Intravitreal BDNF, PEDF or bFGF, or topical BMD afford significant cone neuroprotection in this model.
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A novel simulator model and standardized assessment tools for fine needle aspiration cytology training
(Wiley, 2018-11-25) Jiang, Xiaoyin Sara; Mohammed, Ahmed Abdelraheem Reda; Turic, Iva; Hernández-Sabater, Laura; Caballero-Alemán, Fuensanta; Párraga-Ramírez, Manuel José; Alcaraz Mateos, Eduardo; Poblet Martínez, Enrique; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
Objectives: Fine needle aspiration (FNA) is an invaluable diagnostic procedure for evaluation of lesions; however, acquisition of diagnostic material is dependent on the skill of the practitioner. We report a novel patient simulator for teaching the FNA procedure and structured assessment tools for educators and learners. Methods: We created a novel simulator model for FNA training, employed a standardized teaching module, and assessed procedure utility in medical students. Groups of students completed training using a commercial version of the model, and underwent structured evaluation using an Objective Structured Assessment of Technical Skills (OSATS) form, and the Debriefing Assessment for Simulation in Healthcare (DASH) tool. Results: In the initial phase, 178 students rated the training workshop between valuable and essential (4.2 on a 5-point Likert scale). In the second phase, for students evaluated with the OSATS form, the mean overall score was 33 out of 50 (range 26-43). The areas of weakness for the participants were: (a) compression after the FNA procedure, (b) completion of the informed consent, and (c) correct explanation of the procedure to the patient. For the group of students that completed the DASH questionnaire, the results were: 6.2 (assessment by students) and 6.7 (assessment by instructor) out of a maximum of 7. Conclusion: A realistic simulation model, in combination with a standardized training program with formal assessment methods is a valuable tool to teach FNA. We here describe a process for teaching the FNA procedure to interested educators and learners.
Open Access
A rare cause of intra-abdominal cysts: pancreatic cystic lymphangiomas
(Sociedad Española de Patología Digestiva, 2021) Pérez Fernández, Alejandro; López Martín, Aurelio; Alcaraz Mateos, Eduardo; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
Echenique et al. described a lymphangioma as a rare cystic neoplasm of the pancreas. We present a similar intra-abdominal lesion diagnosed by endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) cytology.
Open Access
Accommodation-related changes in monochromatic aberrations of the human eye as a function of age
(Association for Research in Vision and Ophthalmology (ARVO), 2008-04) López Gil, Norberto; Fernández Sánchez, Vicente; Legras, Richard; Montés Micó, Robert; Lara Lacárcel, Francisco; Nguyen Khoa, Jean Luc; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
PURPOSE. To investigate the relationship between accommodation and the optical aberrations of the whole human eye, as a function of age. METHODS. Sixty healthy subjects with spherical ametropia in the range 3 D, astigmatism less than 1 D, corrected visual acuity of 20/18 or better, and normal findings in an ophthalmic examination were enrolled. Subjects were divided into four groups, with age ranges of 19 to 29, 30 to 39, 40 to 49, and 50 to 60 years. Monochromatic optical aberrations and pupil size were measured with a Hartmann-Shack wavefront sensor under monocular viewing conditions, without pharmacological dilation or cyloplegia. Stimulus vergences were in the range of 0 to 5 D, with an increment of 0.5 D. The change in aberration during accommodation for different groups and different pupil conditions (natural and fixed 4-mm pupil) was compared. RESULTS. Fourth-order spherical aberration (SA) became more negative with accommodation, and the rate of this change was greater in older individuals. For natural pupil conditions, there were no significant differences between age groups in the changes of the higher-order aberrations, coma, and trefoil with accommodation. However, for a 4-mm pupil, the youngest and oldest group showed significant differences in higher order RMS (root mean square) and spherical aberration compared with the other groups. High-order RMS showed a lower increase during accommodation when the pupil accommodative miosis was taken into account (natural pupil condition) than when a fixed 4-mm pupil was used. CONCLUSIONS. Aberrations change with accommodation and with age. SA changes more with accommodation do than other higher-order aberrations. SA becomes more negative with accommodation, and this change is larger in older individuals. Accommodative miosis is useful for ameliorating the increase in higher-order aberrations with accommodation.
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Adenocarcinoma y tumor carcinoide pulmonares sincrónicos. Presentación de dos casos
(Elsevier, 2011-03-31) Aranda Lopez, Francisco Ignacio; Toro, Paula; Alcaraz Mateos, Eduardo; Muci, Tania; Arena, Juan; Teruel, Ana; Peiro, Gloria; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
La asociación de tumor carcinoide y carcinoma broncopulmonar en forma de tumores de aparición sincrónica es excepcional y sólo ha sido publicada en diez ocasiones. En el presente trabajo se describen los hallazgos en 2 pacientes con adenocarcinoma pulmonar en los que en el estudio de la pieza quirúrgica se identificó un tumor carcinoide típico. El hallazgo de un segundo nódulo en un paciente con un carcinoma broncopulmonar, situación cada vez más frecuente por la incorporación de técnicas de imagen con mayor sensibilidad, plantea la necesidad de su evaluación patológica para una correcta estadificación. Un problema adicional es la identificación de segundos nódulos en el curso de la intervención quirúrgica, lo que obliga al estudio intraoperatorio. La correcta valoración de los parámetros morfológicos y su comparación con los del tumor principal puede ser determinante en un correcto diagnóstico y evitar la sobrestadificación.
Open Access
Alpha retinal ganglion cells in pigmented mice retina: number and distribution
(Frontiers Media, 2022-12-01) Gallego Ortega, Alejandro; Norte Muñoz, María; Di Pierdomenico, Johnny; Avilés Trigueros, Marcelino; Villa, Pedro de la; Valiente Soriano, Francisco Javier; Vidal Sanz, Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Óptica y Optometría
Purpose: To identify and characterize numerically and topographically the population of alpha retinal ganglion cells (αRGCs) and their subtypes, the sustained-response ON-center αRGCs (ONs-αRGCs), which correspond to the type 4 intrinsically photosensitive RGCs (M4-ipRGCs), the transient-response ON-center αRGCs (ONt-αRGCs), the sustained-response OFF-center αRGCs (OFFs-αRGCs), and the transient-response OFF-center αRGCs (OFFt-αRGCs) in the adult pigmented mouse retina. Methods: The αRGC population and its subtypes were studied in flat-mounted retinas and radial sections immunodetected against non-phosphorylated high molecular weight neurofilament subunit (SMI-32) or osteopontin (OPN), two αRGCs pan-markers; Calbindin, expressed in ONs-αRGCs, and amacrines; T-box transcription factor T-brain 2 (Tbr2), a key transcriptional regulator for ipRGC development and maintenance, expressed in ipRGCs and GABA-displaced amacrine cells; OPN4, an anti-melanopsin antibody; or Brn3a and Brn3c, markers of RGCs. The total population of RGCs was counted automatically and αRGCs and its subtypes were counted manually, and color-coded neighborhood maps were used for their topographical representation. Results: The total mean number of αRGCs per retina is 2,252 ± 306 SMI32+αRGCs and 2,315 ± 175 OPN+αRGCs (n = 10), representing 5.08% and 5.22% of the total number of RGCs traced from the optic nerve, respectively. αRGCs are distributed throughout the retina, showing a higher density in the temporal hemiretina. ONs-αRGCs represent ≈36% [841 ± 110 cells (n = 10)] of all αRGCs and are located throughout the retina, with the highest density in the temporal region. ONt-αRGCs represent ≈34% [797 ± 146 cells (n = 10)] of all αRGCs and are mainly located in the central retinal region. OFF-αRGCs represent the remaining 32% of total αRGCs and are divided equally between OFFs-αRGCs and OFFt-αRGCs [363 ± 50 cells (n = 10) and 376 ± 36 cells (n = 10), respectively]. OFFs-αRGCs are mainly located in the supero-temporal peripheral region of the retina and OFFt-αRGCs in the mid-peripheral region of the retina, especially in the infero-temporal region. Conclusions: The combination of specific antibodies is a useful tool to identify and study αRGCs and their subtypes. αRGCs are distributed throughout the retina presenting higher density in the temporal area. The sustained ON and OFF response subtypes are mainly located in the periphery while the transient ON and OFF response subtypes are found in the central regions of the retina.
Open Access
Annexin-V binds subpopulation of immune cells altering its interpretation as an in vivo biomarker for apoptosis in the retina
(Ivyspring International Publisher., 2024-11-11) Miyagishima, Kiyoharu J.; Ma, Wenxin; Li, Wei ; Nadal-Nicolás, Francisco Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
In cells undergoing apoptosis phosphatidylserine, a major component of the plasma membrane, translocates to the outer leaflet where it provides eat-me signals for phagocytic recognition and is bound by annexin-V, an apoptotic marker. The need to track retinal ganglion cell death (RGC) in response to glaucomatous damage or optic neuropathy has led to the development of DARC (detection of apoptosing retinal cells) imaging, providing non-invasive, in vivo assessment of RGC death. Although the eye is an immune privileged site, resident and infiltrating immune cells are known to respond quickly to trauma or infection. Some immune cells have binding sites for annexin homologs; thus, their presence may confound estimates of apoptosis measured by annexin-V labeling. The purpose of this study was to re-examine the accuracy of annexin-V apoptotic labeling in the posterior eye and to temporally characterize contributions of non-apoptotic labeling in response to optic nerve (ON) injury. Here, we found annexin-V labeling consists of two phases. Initially, there is a rapid phase matching the time course of apoptotic cell death indicated by cleaved caspase-3 immunostaining observed ex vivo. This is followed by a sustained plateau phase that persists long after the peak of degeneration. We demonstrate that annexin-V binds to a specific subpopulation of myeloid cells in the retina, which were identified using simultaneous confocal scanning laser ophthalmoscopy. Optical coherence tomography and confocal imaging reveal these cells occupy the posterior hyaloid space above the retinal nerve fiber layer and at various retinal depths. Our results highlight the cellular morphological heterogeneity of non-apoptotic annexin-V labeling of retinal microglia. Accordingly, pharmacological depletion of microglia abolishes annexin-V labeling of elongated microglia in vivo revealing fainter labeling of round RGCs. Thus, consideration should be given to the time course of the immune response when interpreting fluorescently labeled annexin-V to visualize retinal cell apoptosis for clinical diagnosis.
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Anogenital distance, a biomarker of prenatal androgen exposure Is associated with prostate cancer severity
(Wiley, 2016-11-16) Maldonado-Cárceles, Ana B.; Sánchez-Rodríguez, Carlos; Vera-Porras, Eva M.; Oñate-Celdrán, Julián; Samper Mateo, Paula; García Escudero, Damián; Torres-Roca, Marcos; Martínez Díaz, Francisco; Arense Gonzalo, Julián Jesús; Mendiola Olivares, Jaime; Torres Cantero, Alberto Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
BACKGROUND. Anogenital distance (AGD), the distance from the centre of the anus to the genitals, is a sexually dimorphic phenotype in mammals. Experimental studies have shown that AGD is a biomarker of prenatal androgen exposure during the masculinisation period of development. The aim of this study is to assess the relationship between anogenital distance (AGD), as an indirect marker of prenatal hormonal environment, and prostate cancer (PCa) severity. MATERIALS. We conducted a cross-sectional study with a total of 120 PCa patients with confirmed biopsy of the tumour from April 2007 to July 2015. Two variants of the anogenital distance were assessed, from the anus to the posterior base of the scrotum (AGDAS) and to the cephalad insertion of the penis (AGDAP). We compared differences in groups to evaluate the association between AGD measurements and severity of the preoperative biopsy and clinical scores. RESULTS. Longer AGDAS was significantly associated with the highest Gleason score (P = 0.015) and D'Amico nomogram (P = 0.048). In contrast, no statistical differences were found in the AGDAP and severity of the preoperative biopsy. CONCLUSIONS. These findings are consistent with the hypothesis that a higher prenatal androgen exposure is associated with higher severity of PCa. Prostate.
Open Access
Apoptotic retinal ganglion cell death after optic nerve transection or crush in mice: delayed RGC loss with BDNF or a Caspase 3 inhibitor
(Association for Research in Vision and Ophthalmology, 2016-01) Sánchez-Migallón, María C.; Valiente Soriano, Francisco Javier; Nadal-Nicolás, Francisco Manuel; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Medicina
Purpose: To investigate retinal ganglion cell (RGC) survival and activation of caspase 3 after optic nerve crush (ONC) or transection (ONT) and treatment with brain-derived neurotrophic factor (BDNF) or Z-DEVD_fmk. Methods: In albino Swiss mice, the left optic nerve was severed or crushed at 0.5 mm from the optic head and retinas were analyzed from 1 to 10 days. Additional groups were treated intravitreally with a single injection of BDNF (2.5 μg) or Z-DEVD_fmk (125 ng) right after injury, or with Z-DEVD_fmk at day 2, or with multiple injections of Z-DEVD_fmk. As controls intact or vehicle-treated retinas were used. In all retinas, Brn3a (RGCs) and cleaved-caspase 3 (c-casp3) were immunodetected and their numbers quantified. In an additional group, c-casp3 expression was assessed in RGCs retrogradely labeled before axotomy. Results: The temporal loss of RGCs was the same after ONC or ONT and occurred in two phases with 65% loss during the first 7 days and an additional 4% loss from day 7 to 10. The appearance of c-casp3+RGCs is Gaussian, peaking at 4 days and declining thereafter. Brn3a down-regulates when RGCs start expressing c-casp3. Retinal ganglion cell rescue rate for BDNF or Z-DEVD_fmk is similar and both delay RGC loss by 1 day. Delayed treatment with Z-DEVD_fmk does not rescue RGCs, and several injections are not better than a single one at the time of the injury. Conclusions: Brn3a down-regulation marks the beginning of RGC death, which after axotomy occurs by caspase-dependent apoptosis in at least half of the RGCs. These data should be considered when designing neuroprotective strategies.
Open Access
Assessment of dry eye symptoms among university students during the COVID-19 pandemic.
(Taylor and Francis, 2021-07-19) García-Ayuso, D; Di Pierdomenico, J.; Moya-Rodríguez, E.; Valiente-Soriano, F.J.; Galindo-Romero, C.; Sobrado-Calvo, P.; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
Clinical relevance: The synchronous hybrid learning environment is associated with increased time spent by students working with VDT and increased prevalence of dry eye symptoms in a university-based population. Background: To assess the prevalence of dry eye symptoms using the ocular surface disease index (OSDI) questionnaire in university students and to identify whether factors such as the synchronous hybrid learning environment as a preventive measure of COVID-19, video display terminal use, gender or contact lens wear influence dry eye symptomatology. Methods: This study was performed using a web-based questionnaire that was distributed to university students to assess questions related to class attendance, to the use of video display terminals, the need for optical correction and, finally, the OSDI questionnaire. Results: A total of 676 university students with an average age of 20.7 ± 2.9 years completed the questionnaire, of which 72.6% (491) were females and 27.4% (185) were males. Only 10.2% of the participants attended face to face classes. Of the participants, 35.5% were contact lens wearers. The mean OSDI score of the study population was 27.68 ± 20.09 and the prevalence of symptomatic dry eye disease (OSDI score above 22) was 51.8%. Female gender (X2(3) = 38.605, p < 0.001), online class attendance (X2(1) = 20.31; p < 0.001), increased hours of online class attendance (X2(2) = 26.84, p < 0.001) and contact lens wear (X2(2) = 15.264, p < 0.05) were associated with a higher incidence of symptomatic dry eye disease. Conclusion: The synchronous hybrid learning environment increases the time students spend working with video display terminals and the prevalence of dry eye symptoms. Female gender and contact lens wear were also associated with a higher prevalence of dry eye symptoms. It should not be ignored that dry eye could also affect academic performance.
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Axotomy-induced retinal ganglion cell death in adult mice: quantitative and topographic time course analyses
(Elsevier, 2011-02-24) Galindo Romero, Caridad; Avilés Trigueros, Marcelino; Jiménez López, Manuel; Valiente Soriano, Francisco Javier; Salinas Navarro, Manuel Ángel; Nadal-Nicolás, Francisco Manuel; Villegas Pérez, Maria Paz; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Anatomía Humana y Psicobiología; Facultades de la UMU::Facultad de Medicina
The fate of retinal ganglion cells after optic nerve injury has been thoroughly described in rat, but not in mice, despite the fact that this species is amply used as a model to study different experimental paradigms that affect retinal ganglion cell population. Here we have analyzed, quantitatively and topographically, the course of mice retinal ganglion cells loss induced by intraorbital nerve transection. To do this, we have doubly identified retinal ganglion cells in all retinas by tracing them from their main retinorecipient area, the superior colliculi, and by their expression of BRN3A (product of Pou4f1 gene). In rat, this transcription factor is expressed by a majority of retinal ganglion cells; however in mice it is not known how many out of the whole population of these neurons express it. Thus, in this work we have assessed, as well, the total population of BRN3A positive retinal ganglion cells. These were automatically quantified in all whole-mounted retinas using a newly developed routine. In control retinas, tracedretinal ganglion cells were automatically quantified, using the previously reported method (SalinasNavarro et al., 2009b). After optic nerve injury, though, traced-retinal ganglion cells had to be manually quantified by retinal sampling and their total population was afterwards inferred. In naïve whole-mounts, the mean ( standard deviation) total number of traced-retinal ganglion cells was 40,437 ( 3196) andofBRN3Apositive ones was 34,697( 1821). Retinal ganglion cell loss was first significant for both markers 5 days post-axotomy and by day 21, the last time point analyzed, only 15% or 12% of traced or BRN3A positive retinal ganglion cells respectively, survived. Isodensity maps showed that, in control retinas, BRN3A and traced-retinal ganglion cells were distributed similarly, being densest in the dorsal retina along the naso-temporal axis. After axotomy the progressive loss of BRN3A positive retinal ganglion cells was diffuse and affected the entire retina. In conclusion, this is the first study assessing the values, in terms of total number and density, of the retinal ganglion cells surviving axotomy from 2 till 21 days post-lesion. Besides, we have demonstrated that BRN3A is expressed by 85.6% of the total retinal ganglion cell population, and because BRN3A positive retinal ganglion cells show the same spatial distribution and temporal course of degeneration than traced ones, BRN3A is a reliable marker to identify, quantify and assess, ex-vivo, retinal ganglion cell loss in this species.
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B-Scan ultrasonography of vitreous dynamics during intravitreal administration of antiangiogenics
(Wolters Kluwer N.V., 2021-11-01) Sánchez-Martínez, Daniel; Sánchez-López, Sara; Sellés-Navarro, Inmaculada; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
Purpose: To study the distribution of angiogenesis inhibitors (anti-Vascular Endothelial Growth Factor) injected into the vitreous cavity by means of simultaneous ultrasonography. Methods: Three hundred and thirty-two B-scan ultrasound sequences of 121 eyes from 95 patients were recorded simultaneously to the intravitreal anti-Vascular Endothelial Growth Factor administration. The dynamics of the injected substance and the presence of reflux were studied, associating them with the presence/absence of total posterior vitreous detachment. Results: Three well-defined patterns were distinguished. Pattern A: the medication penetrates the vitreous in a linear manner until reaching the retina (3.6%, n = 12). Pattern B: the medication adopts a globular shape and then moves down reaching the retrohyaloid space (37%, n = 123). Pattern C: the medication remains in a globular form (54%, n = 180). The pattern was not identified in 17 (5.1%) injections. Pattern A was only observed in vitrectomized eyes. The reflux (7.8%) was exclusive in eyes showing a C pattern. A relationship (P < 0.001) was observed between the presence/absence of total posterior vitreous detachment, the patterns, and the presence of reflux. Conclusion: This study document for the first time the behavior of antiangiogenic medication injected into the vitreous cavity and how its distribution and the presence of reflux is conditioned by the previous state of the vitreous body.
Open Access
BDNF Rescues RGCs But Not Intrinsically Photosensitive RGCs in Ocular Hypertensive Albino Rat Retinas
(Association for Research in Vision and Ophthalmology., 2015-02-26) Valiente Soriano, Francisco Javier; Nadal-Nicolás, Francisco Manuel; Salinas Navarro, Manuel Ángel; Jiménez López, Manuel; Bernal Garro, José M.; Villegas Pérez, Maria Paz; Agudo Barriuso, Marta; Vidal Sanz, Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
Purpose: To study the responses of the general population of retinal ganglion cells (Brn3a(+)RGCs) versus the intrinsically photosensitive RGCs (melanopsin-expressing RGCs [m(+)RGCs]) to ocular hypertension (OHT), the effects of brain-derived neurotrophic factor (BDNF) on the survival of axonally intact and axonally nonintact RGCs, and the correlation of vascular integrity with sectorial RGC loss. Methods: In Sprague-Dawley rats, 5 μg BDNF or vehicle was intravitreally injected into the left eye followed by laser photocoagulation of the limbal tissues. To identify RGCs with an active retrograde axonal transport, Fluorogold was applied to both superior colliculi 1 week before euthanasia (FG(+)RGCs). Retinas were dissected 12 or 15 days after lasering and immunoreacted against Brn3a (to identify all RGCs except m(+)RGCs), melanopsin, or RECA1 (inner retinal vasculature). Results: Ocular hypertension resulted at 12 to 15 days in sectorial loss of FG(+)RGCs (78%-84%, respectively) while Brn3a(+)RGCs were significantly greater, indicating that a substantial proportion (approximately 21%-26%) of RGCs with their retrograde axonal transport impaired survive in the retina. Brain-derived neurotrophic factor increased the survival of Brn3a(+)RGCs to 81% to 67% at 12 to 15 days, respectively. The inner retinal vasculature showed no abnormalities that could account for the sectorial loss of RGCs. At 12 to 15 days, m(+)RGCs decreased to approximately 50% to 51%, but this loss was diffuse across the retina and was not prevented by BDNF. Conclusions: The responses of m(+)RGCs against OHT-induced retinal degeneration and neuroprotection differ from those of Brn3a(+)RGCs; while OHT induces similar loss of Brn3a(+)RGCs and m(+)RGCs, Brn3a(+)RGCs are lost in sectors and can be rescued with BDNF, but m(+)RGCs do not respond to BDNF and their loss is diffuse.
Open Access
Beyond apoptosis: Implications of annexin-V binding to myeloid cells in DARC (Detection of Apoptosing Retinal Cells) imaging
(Wolters Kluwer Health, Medknow Publications, 2026-06) Miyagishima, Kiyoharu J.; Nadal-Nicolás, Francisco Manuel; Li, Wei; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Medicina
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Bilateral early activation of retinal microglial cells in a mouse model of unilateral laser-induced experimental ocular hypertension
(Elsevier, 2018-03-09) Hoz, Rosa de; Ramírez, Ana I.; González Martín, Rosa; Ajoy, Daniel; Rojas, Blanca; Salobrar García, Elena; Valiente Soriano, Francisco J.; Avilés Trigueros, Marcelino; Villegas Pérez, María P.; Vidal Sanz, Manuel; Triviño, Alberto; Ramírez, José M.; Salazar, Juan J.; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
The immune system plays an important role in glaucomatous neurodegeneration. Retinal microglial reactivation associated with ganglion cell loss could reportedly contribute to the glaucoma progression. Recently we have described signs of microglia activation both in contralateral and ocular hypertension (OHT) eyes involving all retinal layers 15 days after OHT laser induction in mice. However, no works available have analyzed the microglial activation at earliest time points after OHT induction (24 h) in this experimental model. Thus, we seek to describe and quantify signs of microglia activation and differences depending on the retinal layer, 24 h after unilateral laser-induced OHT. Two groups of adult Swiss mice were used: age-matched control (naïve) and lasered. In the lasered animals, OHT eyes as well as contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1 and MHC-II. We quantified the number of microglial cells in the photoreceptor layer (OS), outer plexiform layer (OPL), and inner plexiform layer (IPL); the number of microglial vertical processes connecting the OPL and OS; the area of the retina occupied by Iba-1+ cells (Iba1-RA) in the nerve fiber layer-ganglion cell layer (NFL-GCL), the total arbor area of microglial cells in the OPL and IPL and; Iba-1+ cell body area in the OPL, IPL and NFL-GCL. In contralateral and OHT eyes the morphological features of Iba-1+ cell activation were: migration, enlargement of the cell body, higher degree of branching and reorientation of the processes, radial disposition of the soma and processes toward adjacent microglial plexuses, and presence of amoeboid cells acting as macrophages. These signs were more pronounced in OHT eyes. Most of Iba-1+ cells did not express MHC-II; rather, only dendritic and rounded cells expressed it. In comparison with naïve eyes, in OHT eyes and contralateral eyes no significant differences were found in the microglial cell number; but there was a significant increase in Iba1-RA. The total arbor area of microglial cells was significantly decreased in: i) OHT eyes with respect contralateral eyes and naïve-eyes in IPL; ii) OHT eyes with respect to naïve eyes in OPL. The number of microglial vertical processes connecting the OPL and OS were significantly increased in contralateral eyes compared with naïve-eyes and OHT eyes. In OPL, IPL and NFL-GCL, the cell body area of Iba-1+ cells was significantly greater in OHT eyes than in naïve and contralateral eyes, and greater in contralateral eyes than in naïve eyes. A non-proliferative microglial reactivation was detected both in contralateral eyes and in OHT eyes in an early time after unilateral laser-induced OHT (24 h). This fast microglial activation, which involves the contralateral eye, could be mediated by the immune system.
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Brain derived neurotrophic factor maintains Brn3a expression in axotomized rat retinal ganglion cells
(Elsevier, 2009-08-16) Sánchez Migallón, María del Cielo; Nadal-Nicolás, Francisco Manuel; Jiménez López, Manuel; Sobrado Calvo, Paloma; Vidal Sanz, Manuel; Agudo Barriuso, Marta; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultades de la UMU::Facultad de Medicina
The transcription factor Brn3a has been reported to be a good marker for adult rat retinal ganglion cells in control and injured retinas. However, it is still unclear if Brn3a expression declines progressively by the injury itself or otherwise its expression is maintained in retinal ganglion cells that, though being injured, are still alive, as might occur when assessing neuroprotective therapies. Therefore, we have automatically quantified the whole population of surviving Brn3a positive retinal ganglion cells in retinas subjected to intraorbital optic nerve transection and treated with either brain derived neurotrophic factor or vehicle. Brain derived neurotrophic factor is known to delay retinal ganglion cell death after axotomy. Thus, comparison of both groups would inform of the suitability of Brn3a as a retinal ganglion cell marker when testing neuroprotective molecules. As internal control, retinal ganglion cells were, as well, identified in all retinas by retrogradely tracing them with fluorogold. Our data show that at all the analyzed times post-lesion, the numbers of Brn3a positive retinal ganglion cells and of fluorogold positive retinal ganglion cells are significantly higher in the brain derived neurotrophic factor-treated retinas compared to the vehicle-treated ones. Moreover, detailed isodensity maps of the surviving Brn3a positive retinal ganglion cells show that a single injection of brain derived neurotrophic factor protects retinal ganglion cells throughout the entire retina. In conclusion, Brn3a is a reliable retinal ganglion cell marker that can be used to accurately measure the potential effect of a given neuroprotective therapy.
Open Access
Busto de maniquí para simulación médica en punción y aspiración con una aguja
(Oficina Española de Patentes y Marcas, 2025-06-17) Alcaraz Mateos, Eduardo; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica
La presente invención se refiere a un busto de maniqui para simulación medica en puncion y aspiración con una aguja, apto para ser empleado para simulaciones de punción y aspiración con aguja fina (P.A.A.F.); y donde dicho busto de maniqui se encuentra ubicado dentro del sector de docencia medica, dentro de las especialidades de anatomia patologica y radiodiagnóstico.