Orbital glands and drainage conduits are two distinct entities that constitute the lacrimal apparatus system, the malfunction of which leads to a range of ocular surface disorders. Despite the close functional relationship, how the two parts interact under pathophysiological conditions has not been directly tested. The study aims to investigate the lacrimal gland (LG) structural and functional changes upon the drainage system obstruction, thus, testing their function link.

We have determined the presence and cellular distribution of intracellular calcium channels, inositol 1, 4, 5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) in adult and postnatal (P10) lacrimal gland acinar cells. Western blot analysis of both P10 cultures and adult tissue identified the presence of each IP(3)R and RyR isotypes. The immunocytochemistry analysis showed a differential cellular distribution of these calcium channels where the nuclear envelope, endoplasmic reticulum (ER) and Golgi apparatus membranes represent areas with highest levels of channel expression. This IP(3)R and RyR isotype distribution is confirmed by the immuno-EM results. The findings described in this study are in agreement with published pharmacological data that shows the participation of these channels in the secretion process of the lacrimal gland acinar cells. Furthermore, the differential subcellular distribution between the isoforms could indicate a potential role of these intracellular Ca(2+ )channels on the regulation of specific cellular functions.

As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the aqueous part of the tear film, which protects the eye surface. Therefore, a defective LG can lead to serious eyesight impairment. Up to now, little is known about LG morphogenesis and subsequent maturation. In this study, we delineated elements of the cellular and molecular events involved in LG formation by using three epithelial markers, namely aSMA, Krt14, and Krt19. While aSMA marked a restricted epithelial population of the terminal end buds (TEBs) in the forming LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer. Interestingly, Krt19 specifically labeled the presumptive ductal domain and subsequently, the luminal cell layer. By combining these markers, the Fucci reporter mouse strain and genetic fate mapping of the Krt14+ population, we demonstrated that LG epithelium expansion is fuelled by a patterned cell proliferation, and to a lesser extent by epithelial reorganization and possible mesenchymal-to-epithelial transition. We pointed out that this epithelial reorganization, which is associated with apoptosis, regulated the lumen formation. Finally, we showed that the inhibition of Notch signaling prevented the ductal identity from setting, and led to a LG covered by ectopic TEBs. Taken together our results bring a deeper understanding on LG morphogenesis, epithelial domain identity, and organ expansion.

The extraorbital lacrimal glands (ELGs) secret tears to maintain a homeostatic environment for ocular surfaces, and pheromones to mediate social interactions. Although its distinct gender-related differences in mice and rats have been identified, its comprehensive histology together with whole-brain neuronal network remain largely unknown. The primary objective of the present study was to investigate whether sex-specific differences take place in histological and physiological perspectives. Morphological and histological data were obtained via magnetic resonance imaging (MRI), hematoxylin-eosin (HE) staining in mice and rats of both genders. The innervating network was visualized by a pseudorabies virus (PRV) mediated retrograde trans-multi-synaptic tracing system for adult C57BL6/J mice of both genders. In terms of ELGs' anatomy, mice and rats across genders both have 7 main lobes, with one exception observed in female rats which have only 5 lobes. Both female rats and mice generally have relatively smaller shape size, absolute weight, and cell size than males. Our viral tracing revealed a similar trend of innervating patterns antero-posteriorly, but significant gender differences were also observed in the hypothalamus (HY), olfactory areas (OLF), and striatum (STR). Brain regions including piriform area (Pir), post-piriform transition area (TR), central amygdalar nucleus (CEA), medial amygdalar nucleus (MEA), lateral hypothalamic area (LHA), parasubthalamic nucleus (PSTN), pontin reticular nucleus (caudal part) (PRNc), and parabrachial nucleus, (PB) were commonly labeled. In addition, chemical isotope labeling-assisted liquid chromatography-mass spectrometry (CIL-LC-MS) and nuclear magnetic resonance spectroscopy (NMR spectroscopy) were performed to reveal the fatty acids and metabolism of the ELGs, reflecting the relationship between pheromone secretion and brain network. Overall, our results revealed basic properties and the input neural networks for ELGs in both genders of mice, providing a structural basis to analyze the diverse functions of ELGs.

Corneal blindness is the fourth leading cause of blindness worldwide. Since corneal epithelium is constantly renewed, non-integrative gene transfer cannot be used to treat corneal diseases. In many of these diseases, the tear film is defective. Tears are a complex biological fluid secreted by the lacrimal apparatus. Their composition is modulated according to the context. After a corneal wound, the lacrimal gland secretes reflex tears, which contain growth factors supporting the wound healing process. In various pathological contexts, the tear composition can support neither corneal homeostasis nor wound healing. Here, we propose to use the lacrimal gland as bioreactor to produce and secrete specific factors supporting corneal physiology. In this study, we use an AAV2/9-mediated gene transfer to supplement the tear film. First, we demonstrate that a single injection of AAV2/9 is sufficient to transduce all epithelial cell types of the lacrimal gland efficiently and widely. Second, we detect no adverse effect after AAV2/9-mediated nerve growth factor expression in the lacrimal gland. Only a transitory increase in tear flow is measured. Remarkably, AAV2/9 induces an important and long-lasting secretion of this growth factor in the tear film. Altogether, our findings provide a new clinically applicable approach to tackle corneal blindness.

Background: Randomized controlled trials (RCTs) are situated at the top of hierarchy of evidence-based medicine, where its number and quality are important in the assessment of quality of evidence in a medical field. In this study, we aim to assess the status of RCTs in Ophthalmology. Methods: On 15 th of May 2019, we performed a PubMed search for randomized controlled trials published in the field of ophthalmology using relevant filters and search terms. We categorized the results into specific topics in ophthalmology according to Medical Subject Heading (MeSH) database classification system. We used Altmetric explorer to identify journals and articles with the highest number of RCTs and highest citations. Results: We found a total of 540,427 publications in the field of ophthalmology, of which only 11,634 (2.15%) of them were RCTs. 'Retinal diseases' was the topic with the highest number of RCTs, followed by 'glaucoma' and 'conjunctival diseases'. The trial with highest number of citations was on retinal diseases. Only around 18% of all ophthalmology RCTs are published in the top 10 ophthalmology journals, with a maximum percentage of RCTs was (5.53%) published in Ophthalmology. Conclusion: RCTs in ophthalmology primarily concern the retina, glaucoma, and a few other sub-topics, with little focus on sclera, orbit, and the eyelids. Most of the high impact RCTs are published in non-ophthalmology journals.

A new species of an extinct dolphin belonging to the kentriodontids, i.e., Kentriodon sugawarai sp. nov., is described from the upper lower to lowest middle Miocene Kadonosawa Formation in Ninohe City, Iwate Prefecture, northern Japan. The holotype of Kentriodon sugawarai sp. nov., consists of a partial skull with ear bones, mandibular fragments, and some postcranial bones. This new species shares five unique characters with other species of Kentriodon. In addition, the new species differs from other species of the genus in displaying a narrow width of the squamosal lateral to the exoccipital in posterior view, the dorsolateral edge of the opening of the ventral infraorbital foramen that is formed by the maxilla and the lacrimal or the jugal, and at least three anterior dorsal infraorbital foramina. Our phylogenetic analysis based on 393 characters for 103 Odontoceti taxa yielded a consensus tree showing all previously identified kentriodontids as a monophyletic group that comprises the sister group of the crown Dephinoidea, which in turn include Delphinidae, Phocoenidae and Monodontidae. Our analysis also indicates that the distinct innovation of the acoustic apparatus (i.e., 13 out of 29 derived characters are from tympanoperiotic) would have occurred in the ancestral lineage of the Delphinoidea (sensu lato) including the monophyletic Kentriodontidae during their initial evolution and diversification.

Neopterygii is a large group of ray-finned fishes which underwent a rapid radiation in the Middle Triassic. Until recently, 11 stem neopterygians have been recovered from the early Middle Triassic Luoping Biota in eastern Yunnan, China, and they are small to medium-sized fishes. Here, I report the discovery of a new stem neopterygian, Feroxichthys yunnanensis gen. et sp. nov. from the Luoping Biota, which represents the first evidence of large-sized stem neopteygians in this biota with a total length of ~340 mm (290 mm in standard length). The skull of the new taxon is exceptionally well-preserved, showing some peculiar features rarely known in other stem neopterygians, for example fusion of paired premaxillae, fusion of lacrimal with maxilla, and a fused parieto-dermopterotic with a strong posterior process. Phylogenetic studies recover Feroxichthys as a basal colobodontid, and a revised diagnosis of this family is presented. The feeding apparatus indicates that Feroxichthys might have been predominantly durophagous, resembling other colobodontids. However, the anterior peg-like teeth in the jaws of Feroxichthys are much longer and stronger than other colobodontids, enabling a more powerful initial prey capture before food was passed posteriorly to molariform teeth for crushing in the oral cavity. As a mysterious large durophagous predator previously unknown from the Luoping Biota, the new finding is important not only for understanding the early diversification of neopterygians during this age but also for investigating the trophic structure in this marine ecosystem.

Neopterygii is a taxonomically diverse clade of ray-finned fishes, including Teleostei, Holostei and closely related fossil taxa. The Colobodontidae is a stem group of large-sized neopterygians with a durophagous feeding adaption from the Middle to Late Triassic marine ecosystems in Europe and South China. Here, we report the discovery of a new colobodontid, Feroxichthys panzhouensis sp. nov., based on a well-preserved specimen from the early Middle Triassic (Anisian) of Panzhou (formerly known as Panxian), Guizhou, China. The discovery extends the geographical distribution of Feroxichthys from eastern Yunnan into western Guizhou, and demonstrates a more rapid diversification of early colobodontids than previously thought. The new species possesses diagnostic features of Feroxichthys (e.g., a fused lacrimal-maxilla), but it is easily distinguished from the type species Feroxichthys yunnanensis and other colobodontids by some derived features on the skull and, especially, the relatively short and deep body with a prominent postcranial hump. This body form, previously unknown in colobodontids, implicates a morphological adaptation to structurally complex habitats in light of ecological studies of modern ray-finned fishes with a similar body form. In addition, the feeding apparatus suggests a more obligate durophagous diet for F. panzhouensis sp. nov. than other colobodontids. Results of a cladistic analysis recover the new species as a sister taxon of F. yunnanensis within the Colobodontidae, and suggest that a hump-backed body form has independently evolved multiple times in Triassic neopterygians. As such, the new finding provides an important addition for our understanding of the morphological and ecological diversity of neopterygian fishes from the Triassic marine ecosystems in South China.