Morphological factors associated with giant vacuoles with I-pores in Schlemm's canal endothelial cells of human eyes: A serial block-face scanning electron microscopy study.

Increased intraocular pressure (IOP) is the main risk factor for primary open-angle glaucoma and results from impaired drainage of aqueous humor (AH) through the trabecular outflow pathway. AH must pass the inner wall (IW) endothelium of Schlemm's canal (SC), which is a monolayer held together by tight junctions, to exit the eye. One route across the IW is through giant vacuoles (GVs) with their basal openings and intracellular pores (I-pores). AH drainage through the trabecular outflow pathway is segmental. Whether more GVs with both basal openings and I-pores are present in the active flow areas and factors that may influence formation of GVs with I-pores have not been fully elucidated due to limitations in imaging methods. In this study, we applied a relatively new technique, serial block-face scanning electron microscopy (SBF-SEM), to investigate morphological factors associated with GVs with I-pores in different flow areas. Two normal human donor eyes were perfused at 15 mmHg with fluorescent tracers to label the outflow pattern followed by perfusion-fixation. Six radial wedges of trabecular meshwork including SC (2 each from high-, low-, and non-flow areas) were imaged using SBF-SEM (total: 9802 images). Total GVs, I-pores, basal openings, and four types of GVs were identified. Percentages of GVs with I-pores and basal openings and number of I-pores/GV were determined. Overall, 14.4% (477/3302) of GVs had I-pores. Overall percentage of GVs with both I-pores and basal openings was higher in high- (15.7%), than low- (12.6%) or non-flow (7.3%) areas. Of GVs with I-pores, 83.2% had a single I-pore; 16.8% had multiple I-pores (range: 2-6). Additionally, 180 GVs (90 with I-pores and 90 without I-pores) were randomly selected, manually segmented, and three-dimensionally (3D) reconstructed to determine size, shape, and thickness of the cellular lining. Size of GVs (including median volume, surface area, and maximal cross-sectional area) with I-pores (n = 90) was significantly larger than GVs without I-pores (n = 90) using 3D-reconstructed GVs (P ≤ 0.01). Most I-pores (73.3%; 66/90) were located on or close to GV's maximal cross-sectional area with significant thinning of the cellular lining. Our results suggest that larger size and thinner cellular lining of GVs may contribute to formation of GVs with I-pores. More GVs with I-pores and basal openings were observed in high-flow areas, suggesting these GVs do provide a channel through which AH passes into SC and that increasing this type of GV may be a potential strategy to increase aqueous outflow for glaucoma treatment.

Vision does not impact walking performance in Argentine ants.

Many walking insects use vision for long-distance navigation, but the influence of vision on rapid walking performance that requires close-range obstacle detection and directing the limbs towards stable footholds remains largely untested. We compared Argentine ant (Linepithema humile) workers in light versus darkness while traversing flat and uneven terrain. In darkness, ants reduced flat-ground walking speeds by only 5%. Similarly, the approach speed and time to cross a step obstacle were not significantly affected by lack of lighting. To determine whether tactile sensing might compensate for vision loss, we tracked antennal motion and observed shifts in spatiotemporal activity as a result of terrain structure but not illumination. Together, these findings suggest that vision does not impact walking performance in Argentine ant workers. Our results help contextualize eye variation across ants, including subterranean, nocturnal and eyeless species that walk in complete darkness. More broadly, our findings highlight the importance of integrating vision, proprioception and tactile sensing for robust locomotion in unstructured environments.

Optic-nerve-transmitted eyeshine, a new type of light emission from fish eyes.

BACKGROUND: Most animal eyes feature an opaque pigmented eyecup to assure that light can enter from one direction only. We challenge this dogma by describing a previously unknown form of eyeshine resulting from light that enters the eye through the top of the head and optic nerve, eventually emanating through the pupil as a narrow beam: the Optic-Nerve-Transmitted (ONT) eyeshine. We characterize ONT eyeshine in the triplefin blenny Tripterygion delaisi (Tripterygiidae) in comparison to three other teleost species, using behavioural and anatomical observations, spectrophotometry, histology, and magnetic resonance imaging. The study's aim is to identify the factors that determine ONT eyeshine occurrence and intensity, and whether these are specifically adapted for that purpose. RESULTS: ONT eyeshine intensity benefits from locally reduced head pigmentation, a thin skull, the gap between eyes and forebrain, the potential light-guiding properties of the optic nerve, and, most importantly, a short distance between the head surface and the optic nerves. CONCLUSIONS: The generality of these factors and the lack of specifically adapted features implies that ONT eyeshine is widespread among small fish species. Nevertheless, its intensity varies considerably, depending on the specific combination and varying expression of common anatomical features. We discuss whether ONT eyeshine might affect visual performance, and speculate about possible functions such as predator detection, camouflage, and intraspecific communication.

Post-GWAS functional analyses of CNTNAP5 suggests its role in glaucomatous neurodegeneration.

Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based GWAS, we identified a novel CNTNAP5 genic region, significantly associated with PACG. In the current study, we have extended our perception of CNTNAP5 involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of cntnap5 by translation-blocking morpholinos. While cntnap5 knockdown was successfully validated using an antibody, immunofluorescence followed by western blot analyses in cntnap5-morphant (MO) zebrafish revealed increased expression of acetylated tubulin indicative of perturbed cytoarchitecture of retinal layers. Moreover, significant loss of Nissl substance is observed in the neuro-retinal layers of cntnap5-MO zebrafish eye, indicating neurodegeneration. Additionally, in spontaneous movement behavioural analysis, cntnap5-MO zebrafish have a significantly lower average distance traversed in light phase compared to mismatch-controls, whereas no significant difference was observed in the dark phase, corroborating with vision loss in the cntnap5-MO zebrafish. This study provides the first direct functional evidence of a putative role of CNTNAP5 in visual neurodegeneration.

The Segment, Slice, and 3D Print (SS3DP) Workflow of 3D Printing Eye Anatomy for Clinicians: A Proof-of-Concept Study.

3D printing is becoming increasingly important as time passes, with the latest technologies driving innovation in many fields, including ophthalmology. However, more is needed to know how clinicians can become innovators in their daily practice without needing expert engineering knowledge of the underlying technologies. We aimed to address that shortcoming by developing a pipeline clinicians can use to 3D print. This workflow was named SS3DP: Segment, Slice, and 3D Print. It was tested by fabricating a 3D-printed eyeball. In terms of the results of this work, we observed that the segmentation process was imperfect due to the difficulty of segmenting small structures. The learning curve was steep initially, but the technique improved the more time spent on the segmentation platform. No quantitative analysis was carried out. Innovation in medicine is stifled if its leading participants, clinicians, cannot engage with it due to a lack of knowledge.

Nanocarriers for ocular drug delivery: Recent advances and future opportunities.

Topical route of administration is very important and the most commonly used method of drug delivery for treatment of ocular diseases. However, due to unique anatomical and physiological barriers of eye, it is difficult to achieve the therapeutic concentration in the targeted tissue within the eye. To overcome the effect of these barriers in absorption and to provide targeted and sustained drug delivery, various advances have been made in developing safe and efficient drug delivery systems. Various formulation strategies for ocular drug delivery are used, like basic formulation techniques for improving availability of drugs, viscosity enhancers, and use of mucoadhesives for drug retention and penetration enhancers to promote drug transport to the eye. In this review, we present a summary of the current literature to understand the anatomical and physiological limitations in achieving adequate ocular bioavailability and targeted drug delivery of topically applied drugs and use of new techniques in formulating dosage forms in overcoming these limitations. The recent and future advances in nanocarrier-mediated drug delivery may have the potential to provide patient-friendly and noninvasive techniques for the treatment of diseases related to the anterior and posterior segments of the eye.

Topical drug delivery to the retina: obstacles and routes to success.

INTRODUCTION: Retinal diseases are one of the main reasons for vision loss where all available drug treatments are based on invasive drug administration such as intravitreal injections. Despite huge efforts and some promising results in animal models, almost all delivery technologies tested have failed in human trials. There are however examples of clinically effective topical delivery systems such as fast dissolving aqueous eye drop suspensions. AREAS COVERED: Six obstacles to topical drug delivery to the eye have been identified and discussed in some details. These obstacles consist of static membrane barriers to drug permeation into the eye, dynamic barriers such as the lacrimal drainage and physiochemical barriers such as low thermodynamic activity. It is explained how and why these obstacles hamper drug permeation and how different technologies, both those that are applied in marketed drug products and those that are under investigation, have addressed these obstacles. EXPERT OPINION: The reason that most topical drug delivery systems have failed to deliver therapeutic drug concentrations to the retina is that they do not address physiochemical barriers such as the thermodynamic activity of the permeating drug molecules. Topical drug delivery to the retina has only been successful when the static, dynamic, and physiochemical barriers are addressed simultaneously.

The contribution of scholars to the anatomy of the eye and adnexa in islamic geography.

From the early period of Islam, Muslim scholars have translated the ancient Greek medical works, and they reached a much more advanced level. Blindness was a major cause of disability in all Islamic geography, so physicians from Islamic territory, particularly Yuhanna ibn Masawayh, Hunain Ibn Ishaq, Rhazes, Ali bin Isa, Ibn-i Sina, and Ibn Al-Haitam, were particularly focused on the anatomy of the eye and diagnosis and treatment of eye diseases. In this study, we aimed to report the contributions of the Muslim scholar on the anatomy of the eye and adnexa for the first time in the literature.

Persistent Tunica Vasculosa Lentis in Full-Term Infants: A Report of Two Cases.

This is a report of rare cases of full-term infants born with persistent tunica vasculosa lentis (TVL) with no retinopathy of prematurity (ROP) and no plus disease. This condition can be mistaken with iris vascular enlargement-associated plus disease, leading to unnecessary laser or intravitreal injections. The cases were treated with close observation, which resulted in complete resolution of the TVL. In conclusion, we encourage the diagnosis of TVL and careful monitoring of such cases before the intervention, as the condition may revert completely.

Development of In Vitro Corneal Models: Opportunity for Pharmacological Testing.

The human eye is a specialized organ with a complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years, many in vitro models have been developed in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review, the ocular cell types and functionality are described, providing an overview about the scientific challenge for the development of three-dimensional (3D) in vitro models.

More Than Meets the Eye: The Contributions of John Dalrymple (1803-1852).

Having authored two major ophthalmology textbooks and honored with the eponym, the "Dalrymple sign," many are familiar with the works of Dr. John Dalrymple when it comes to the eye. However, few are aware of his other, numerous and wide-ranging contributions to the fields of science and medicine. In this article, we discuss the life and work of a man dedicated to the pursuit and advancement of knowledge and education.

Should the annular tendon of the eye be named 'annulus of Zinn' or 'of Valsalva'?

The annular tendon is commonly named 'annulus of Zinn', from the German anatomist and botanist Johann Gottfried Zinn (1727-1759) who described this structure in his Descriptio anatomica oculi humani (Anatomical Description of the Human Eye, 1755). This structure, however, had been previously discovered not by Zinn, but by Antonio Maria Valsalva (1666-1723) some decades before the publication of Zinn, in his Dissertatio anatomica prima and Dissertatio anatomica altera (First and Second Anatomical Dissertations), inside Valsalva's Opera omnia published in 1740. We advance that this structure could be re-named such as 'annulus of Valsalva-Zinn' because Valsalva, even making a mistake in its functional interpretation, first described this anatomical structure. Likewise, Valsalva, with his discovery, advanced a revolutionary idea for that time on the usefulness of anatomy for clinic and pathology.