Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs) in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5) and postnatal (P0, P3, P7) kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage), and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1) VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2) their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3) peritubular capillary VE-PTP expression is down-regulated in adult kidneys, suggesting a role of VE-PTP in the development of peritubular capillaries.

The cumulative knowledge of retina development has been instrumental in the generation of retinal organoid systems from pluripotent stem cells; and these three-dimensional organoid models, in turn, have provided unprecedented opportunities for retinal research and translational applications, including the ability to model disease in a human setting and to apply these models to the development and validation of therapeutic drugs. In this review article, we examine how retinal organoids can also contribute to our understanding of retinal developmental mechanisms, how this knowledge can be applied to modeling developmental abnormalities, and highlight some of the avenues that remain to be explored.

The development of stem cell technologies has opened up new opportunities for research and therapeutic development that, until recently, were unavailable. In particular, the development of human stem cell derived 3D tissues or “organoids” that recapitulate the native histoarchitecture, and to some degree the native functionality, have provided incredible advancements in our understanding of human physiology and disease. In this study we take advantage of retinal organoids as a new model to study the mechanisms of cell death affecting retinal ganglion cells during human development. Human induced pluripotent stem cells (hiPSC) were directed to follow a neuronal lineage and were then further differentiated into 3D retinal tissue. Retinal organoids were collected at various time points during development and analyzed using Western blot and immunofluorescent staining for retinal ganglion cells and programmed cell death markers. Our results show the role of programmed cell death as a mechanism to control retinal ganglion cell numbers during development. This has important consequences for understanding not only basic developmental processes, but also the basis of congenital retinal abnormalities that can lead to diseases of vision. Moreover, this knowledge has potential impact for translational research using retinal organoid models. Support or Funding Information This work was supported, in part, by a Challenge Grant to the Department of Ophthalmology at the University of Colorado from Research to Prevent Blindness.

With reduced contact hours and increasing concern regarding inadequate anatomical knowledge, anatomy education in the medical curriculum must be robust and efficient. Although cadaveric dissection is the traditional approach to teaching anatomy, dissection has many limitations, such as high cost, time‐consuming labor, limited availability of cadavers, and lack of qualified instructors. To address this challenge, alternatives to cadaver‐based instruction, such as plastinates, are routinely used as supplemental teaching resources. By replacing water and adipose tissue with polymers, plastination allows the long‐term preservation of well‐dissected cadaveric specimens. Despite the advantages of plastination, use of plastinates may be limited by high production and maintenance costs. Currently, the Modern Human Anatomy Program at the University of Colorado Anschutz Medical Campus has one plastinate of the female reproductive tract, bisected to show the internal anatomy together with the external genitalia and urinary bladder. Although the plastinate was well‐received in a small‐sized graduate course, incorporating a singular plastinate in a large medical class is problematic. Thus, implementing a three‐dimensional (3D) digital model of a plastinate may be an effective method to accommodate large class sizes without compromising the physical specimen or adding substantial costs. The aim of this project was to iteratively design and develop a mobile application (app) depicting a 3D model of the plastinated female reproductive tract. A 3D surface model of the plastinate was digitally reconstructed using an Artec Space Spider 3D Scanner. Artifacts were smoothed and texture was refined in ZBrushCore 2018 and Autodesk Maya 2019. The model was packaged into a mobile app using a game engine, Unreal Engine 4 (UE4). Compared to other app development software, UE4 was chosen for its robust visualization of 3D models, cross‐platform deployment, and zero upfront costs. With online tutorials, UE4’s Blueprints visual scripting system is relatively simple to grasp, and the node‐based interface is a powerful approach for non‐programmers, allowing extreme flexibility without the need for coding. Utilizing this flexibility, the app was designed to promote self‐paced independent learning of the female reproductive tract and associated pelvic anatomy. Students can follow a pre‐determined learning module or freely navigate through highlighted and annotated structures on the bisected model. In addition to basic manipulation of the model, the app features interactive quizzes to encourage active learning. The app can also be used alongside the original plastinate to aid students in structure identification. By digitizing cadaver anatomy, the mobile app ensures a realistic and accurate representation of human anatomy and any anatomical variations or pathologies. Integrating supplemental resources, such as an interactive mobile app, may allow instructors to strengthen anatomy education and address barriers to cadaver‐based instruction. Further ...

Pelvic organ prolapses are becoming more prevalent, with the number of diagnoses projected to increase by 46% in the United States by 2050. One type of prolapse is enterocele, a condition in which a peritoneal sac containing the small intestines herniates into the vaginal wall. Secondary to weakened pelvic floor muscles, enterocele is strongly associated with hysterectomy, with 60% of women diagnosed with enterocele having a past history of hysterectomy. Healthcare providers discover prolapse during a physical exam when the vaginal wall bulges outside the vaginal opening. Despite the increasing prevalence and complicated anatomy of enterocele, there are few resources to educate women on the anatomy of a prolapse. Knowledge gaps cause patients stress and shame surrounding their condition, limiting their ability to confide in others and seek medical advice. Thus, supplementing counseling with patient education resources on enterocele anatomy may increase patient understanding and improve communication between patient and provider. Effective counseling may decrease patient anxiety by addressing patient fears, relieving humiliation, and putting an end to self‐blame. The first aim of this project was to develop an interactive three‐dimensional (3D) mobile application (app) to assist healthcare providers in educating post‐hysterectomy women on the anatomy of enterocele. The second aim was to assess the educational value of the mobile app as a visual aid during counseling and its ability to increase patient understanding and decrease anxiety. The 3D model utilized in the app was segmented using 3D Slicer from a de‐identified CT urogram and pelvic MRI of a female diagnosed with enterocele post‐hysterectomy. Artifacts were smoothed in ZBrushCore 2018, and the model was animated in Autodesk Maya 2019. The model was imported into a game engine, Unreal Engine 4, and packaged into a mobile app, which was iteratively designed to highlight relevant structures of pelvic anatomy and allow the model to be enlarged and rotated. The mobile app was revised based on surveys from healthcare providers on the app’s usability and educational value. To test the efficacy of the app, patients were randomized into two groups: (1) a control group with standard counseling and (2) an experimental group with counseling supplemented by the mobile app. Patients completed pre‐ and post‐intervention surveys assessing anatomical understanding and anxiety regarding their diagnosis. Preliminary data suggest the mobile app has a high potential to assist healthcare providers with educating patients. Complete analysis of patient and clinician data will be presented. Women’s perspectives and issues are traditionally underrepresented in medicine. By developing a mobile app to increase awareness, we intend to normalize the conversation and overcome the social stigma of female pelvic organ prolapse.