Creation of an Isogenic Human iPSC-Based RGC Model of Dominant Optic Atrophy Harboring the Pathogenic Variant c.1861C>T (p.Gln621Ter) in the OPA1 Gene.

Autosomal dominant optic atrophy (ADOA) is a rare progressive disease mainly caused by mutations in OPA1, a nuclear gene encoding for a mitochondrial protein that plays an essential role in mitochondrial dynamics, cell survival, oxidative phosphorylation, and mtDNA maintenance. ADOA is characterized by the degeneration of retinal ganglion cells (RGCs). This causes visual loss, which can lead to legal blindness in many cases. Nowadays, there is no effective treatment for ADOA. In this article, we have established an isogenic human RGC model for ADOA using iPSC technology and the genome editing tool CRISPR/Cas9 from a previously generated iPSC line of an ADOA plus patient harboring the pathogenic variant NM_015560.3: c.1861C>T (p.Gln621Ter) in heterozygosis in OPA1. To this end, a protocol based on supplementing the iPSC culture media with several small molecules and defined factors trying to mimic embryonic development has been employed. Subsequently, the created model was validated, confirming the presence of a defect of intergenomic communication, impaired mitochondrial respiration, and an increase in apoptosis and ROS generation. Finally, we propose the analysis of OPA1 expression by qPCR as an easy read-out method to carry out future drug screening studies using the created RGC model. In summary, this model provides a useful platform for further investigation of the underlying pathophysiological mechanisms of ADOA plus and for testing compounds with potential pharmacological action.

Expresión de tuftelina en gérmenes dentales humanos / Expression of tuftelin in human dental germs

La tuftelina es una proteína secretada en la matriz adamantina en desarrollo durante la formación del esmalte. Su función continúa sin esclarecerse, aunque se presume que juega un papel importante en la biomineralización de esmalte y dentina, así como en el desarrollo del órgano dental. Con el presente estudio se identificó su localización en las diferentes estructuras de gérmenes dentales de fetos humanos, conforme a los resultados se observó su expresión en el estadio pre-secretor observándose en el citoplasma de los ameloblastos, retículo estrellado, papila dental, así como en el estrato intermedio; en el secretor se identificó principalmente en la unión amelodentinaria, y en la superficie externa del esmalte, observando una marcada expresión de la proteína en la porción basal del proceso odontoblástico, pero no en la matriz extracelular de la dentina. De acuerdo a los resultados obtenidos se puede considerar que su expresión se presenta tanto en la amelogénesis, como en la odontogénesis en tejidos sin mineralizar.

The tuftelin is a secreted protein in the adamantine matrix in developing during the enamel formation. Its function continues unclarified, although it plays a role in the biomineralization of the dental organ. With the present studio the location was identified in the different structures of dental germs from human fetuses, according to the results it was observed the expression in the pre-secretor stage being observed in the cytoplasm of ameloblasts, stellate reticulum, dental papilla, also in the intermediate stratum; in the secretor it was mainly identified in the amelodentinal junction and in the outer surface of enamel, observing a marked expression of the protein in the basal portion of the odontoblastic process, but not in the extracellular matrix of the dentine. According to the results obtained it can be considered that its expression occurs in both amelogenesis and odontegenesis in unmineralized tissues.

Estudio transversal comparativo de la relación maxilo-mandibular de McNamara aplicadas a sujetos mexicanos / Transversal comparative study of McNamara maxillofacial mandibular ratio applied in Mexican subjects

Las características antropológicas entre diversas razas en las cuales se incluyen etnia, sexo y edad en el mundo varían, es preciso analizar que un estudio establecido para una población no puede ser usado para otra, ya que presenta formas y características diferentes; es por esto que existe la necesidad de realizar estudios en diversas razas comparándolos con las normas establecidas. El objetivo fue comparar la relación maxilo-mandibular de McNamara aplicadas en sujetos mexicanos. Se analizaron 60 radiografías laterales de cráneo con trazados de McNamara. Se identificaron diferencias en los patrones genéticos de crecimiento de los caucásicos y los mexicanos. Nuestros resultados muestran un crecimiento típico de los pacientes clase II esqueletal con maxilar hipotónico posteroanteriormente, una mandíbula disminuida y poca altura vertical, esto como consecuencia de una falta de crecimiento del tercio medio facial por una pobre ventilación aérea.

The anthropological characteristics between different races in which ethnicity, sex and age vary in the world, and it becomes necessary to analyze a set for one population study that cannot be used for another, with different shapes and characteristics. There is a need for studies in different races for comparison with established standards. The objective of the research was to compare the McNamara maxilla-mandibular relationship applied in Mexicans subjects and analyze 60 lateral radiographs of the skulls with McNamara traces. Genetic differences in growth patterns of Caucasians and Mexicans were identified. Our results show typical growth of skeletal class II patients with hypotonic posterior jaw, and jaw with diminished vertical height caused by a lack of midface growth the result of poor air flow.