The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor is a master regulator of the epithelial to mesenchymal transition (EMT), and of the reverse mesenchymal to epithelial transition (MET) processes. ZEB1 plays an integral role in mediating cell state transitions during cell lineage specification, wound healing and disease. EMT/MET are characterized by distinct changes in molecular and cellular phenotype that are generally context-independent. Posterior polymorphous corneal dystrophy (PPCD), associated with ZEB1 insufficiency, provides a new biological context in which to understand and evaluate the classic EMT/MET paradigm. PPCD is characterized by a cadherin-switch and transition to an epithelial-like transcriptomic and cellular phenotype, which we study in a cell-based model of PPCD generated using CRISPR-Cas9-mediated ZEB1 knockout in corneal endothelial cells (CEnCs). Transcriptomic and functional studies support the hypothesis that CEnC undergo a MET-like transition in PPCD, termed endothelial to epithelial transition (EnET), and lead to the conclusion that EnET may be considered a corollary to the classic EMT/MET paradigm.

The intention of utilizing chaperones during sensitive physical exams is to show respect to the patient, while simultaneously providing protection to both the patient and the medical provider. Despite clinical practice recommendations to offer chaperones for sensitive urologic exams, there is no data regarding the consistency of chaperone utilization. Our aim was to summarize the patient and provider perspectives on the role of chaperones in urology as well as identify barriers to implement chaperone consistency. In the present investigation, we conducted a systematic review of prospective, case-control, and retrospective studies and followed the PRISMA 2020 guidelines for data reporting. Studies were identified from PubMed, MEDLINE, and PMC using the Medical Subject Headings (MeSH) terms “chaperones, patient”, “chaperones, medical”, and keywords “chaperones”, and “urology”. Studies were included if they addressed patient/provider perspectives on chaperone utilization in urology specifically and were excluded if they investigated perspectives on chaperone utilization in other specialties. Preliminary study identification yielded 702 studies, 9 of which were eligible for this review after applying the inclusion and exclusion criteria. Of these, 4 studies focused on the patient perspective and 5 focused on the provider perspective. The percentage of patients that did not have a chaperone present during their urologic exam ranged from 52.9-88.5%. A greater proportion of these patients were male. Patients (59%) prefer a family member compared to a staff member as a chaperone. Physicians (60%) prefer staff member chaperones compared to family members. One study reported that 25.6% of patients did not feel comfortable to ask for a chaperone if they were not offered one. Two studies reported the percentage of patients who believed chaperones should be offered to all urology patients, ranging from 73-88.4%. Three studies reported the use of chaperones in the clinic which ranged from 5-72.5%. Two studies reported chaperone utilization documentation, ranging between 16-21.3%. Two studies reported the likelihood of chaperone utilization depending on gender of the physician, showing that male physicians were more likely to utilize chaperones and were 3x more likely to offer chaperones to their patients compared to female physicians. Research suggests that there are differing perspectives between patients and physicians regarding the specific role and benefits chaperones offer during a sensitive urologic examination, as well as differences in preferences of who should perform the role of the chaperone. While more work needs to be done to bridge the divide between clinical practice and patient/physician preferences, the act of offering chaperones to urologic patients, regardless if they want to utilize a chaperone for their examination is respectful of patient privacy and decision making.

PurposeMacular Corneal Dystrophy (MCD, MIM #217800) is a category 1 corneal stromal dystrophy as per the current IC3D classification. While characterized by macular stromal deposits, we report a case of MCD type II with isolated bilateral peripheral Decemet membrane opacities, describing the clinical features and results of screening the CHST6 gene and serum sulfated keratan sulfate levels.ObservationsA 68-year-old man with an unremarkable past medical and family history presented with bilateral progressive decrease in vision. Ocular exam revealed bilateral clear corneas with the exception of peripheral, round, gray-white discrete deposits at the level of Descemet membrane and decreased central corneal thickness in both eyes. The morphology of the corneal deposits, decreased corneal thickness and the absence of a family history were consistent with MCD, prompting screening of the CHST6 gene. Sanger sequencing followed by allele specific cloning revealed compound heterozygous CHST6 mutations in trans configuration: c.-26C > A, which created a new upstream open reading frame (uORF’), predicted to attenuate translation efficiency of the downstream main ORF; and c.803A > G (p.(Tyr268Cys)), previously associated with MCD. Serum keratan sulfate was reduced but detectable, consistent with the diagnosis of macular corneal dystrophy type II.ConclusionsAlthough macular corneal dystrophy is classified as a corneal stromal dystrophy with endothelial involvement, we report a case of MCD with dystrophic deposits confined to the peripheral Descemet membrane, indicating that MCD may be associated with isolated endothelial involvement.

AJA) 34 ZEB1 and corneal endothelial cell biology 2 ABSTRACT 35The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor is a master regulator of 36 the epithelial to mesenchymal transition (EMT), and of the reverse mesenchymal to epithelial 37 transition (MET) processes. ZEB1 plays an integral role in mediating cell state transitions during 38 cell lineage specification, wound healing and disease. EMT/MET are characterized by distinct 39 changes in molecular and cellular phenotype that are generally context-independent. Posterior 40 polymorphous corneal dystrophy (PPCD), associated with ZEB1 insufficiency, provides a new 41 biological context in which to understand and evaluate the classic EMT/MET paradigm. PPCD is 42 characterized by a cadherin-switch and transition to an epithelial-like transcriptomic and cellular 43 phenotype, which we study in a cell-based model of PPCD generated using CRISPR-Cas9-44 mediated ZEB1 knockout in corneal endothelial cells (CEnCs). Transcriptomic and functional 45 studies support the hypothesis that CEnC undergo a MET-like transition in PPCD, termed 46 endothelial to epithelial transition (EnET), and lead to the conclusion that EnET may be 47 (EMT) or the reverse process, mesenchymal to epithelial (MET). EMT is characterized by 54 distinct molecular and morphologic changes in which epithelial cells lose an epithelial-associated 55 gene expression profile, apicobasal polarity and intercellular adhesions, and gain a mesenchymal-56 associated gene expression profile and increased migratory capacity. Conversely, the reverse of 57 the EMT process effectively characterizes MET. EMT and MET are tightly regulated CST 58 processes involving the regulation of many genes in a cell-type-independent manner, and for 59 which stable transition states have been identified [2][3][4][5][6][7]. For example, the cadherin-switch, a well-60 described feature of EMT, involves the repression of cadherin 1 (CDH1; E-cadherin) and 61 activation of cadherin 2 (CDH2; N-cadherin) gene expression, with the reverse being observed in 62MET. In addition, an inverse correlation is observed between the mesenchymal-associated 63 transcription factor ZEB1 and two epithelial-associated transcription factors, ovo-like 2 (OVOL2) 64 and grainy head-like transcription factor 2 (GRHL2), known to directly repress ZEB1 65 transcription [6,[8][9][10]. 66The corneal endothelium is present on the internal surface of the cornea, which is 67 comprised of three cell types: the external corneal epithelium, the central connective tissue 68 containing a "resting" fibroblast-like cell type (i.e., keratocytes), and the corneal endothelium. 69The corneal endothelium demonstrates an epithelial organization (i.e., simple squamous 70 epithelium), and expresses both epithelial-and mesenchymal-associated genes [11]. Nevertheless, 71 corneal endothelial cells (CEnC) are considered distinct from most epithelial cell types due to 72 their embryonic origin, unique function and gene expression profile [11]. Therefore, based on 73 anato...

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