Mechanical Load and Piezo1 Channel Regulated Myosin II Activity in Mouse Lenses.

The cytoarchitecture and tensile characteristics of ocular lenses play a crucial role in maintaining their transparency and deformability, respectively, which are properties required for the light focusing function of ocular lens. Calcium-dependent myosin-II-regulated contractile characteristics and mechanosensitive ion channel activities are presumed to influence lens shape change and clarity. Here, we investigated the effects of load-induced force and the activity of Piezo channels on mouse lens myosin II activity. Expression of the Piezo1 channel was evident in the mouse lens based on immunoblot and immufluorescence analyses and with the use of a Piezo1-tdT transgenic mouse model. Under ex vivo conditions, change in lens shape induced by the load decreased myosin light chain (MLC) phosphorylation. While the activation of Piezo1 by Yoda1 for one hour led to an increase in the levels of phosphorylated MLC, Yoda1 treatment for an extended period led to opacification in association with increased calpain activity and degradation of membrane proteins in ex vivo mouse lenses. In contrast, inhibition of Piezo1 by GsMTx4 decreased MLC phosphorylation but did not affect the lens tensile properties. This exploratory study reveals a role for the mechanical load and Piezo1 channel activity in the regulation of myosin II activity in lens, which could be relevant to lens shape change during accommodation.

Ankyrin-B is required for the establishment and maintenance of lens cytoarchitecture, mechanics, and clarity.

This study illustrates a vital role for ankyrin-B in lens architecture, growth and function through its involvement in membrane protein and spectrin-actin cytoskeletal organization and stability The transparent ocular lens is essential for vision by focusing light onto the retina. Despite recognizing the importance of its unique cellular architecture and mechanical properties, the molecular mechanisms governing these attributes remain elusive. This study aims to elucidate the role of ankyrin-B (AnkB), a membrane scaffolding protein, in lens cytoarchitecture, growth and function using a conditional knockout (cKO) mouse model. AnkB cKO mouse has no defects in lens morphogenesis, but exhibited changes that supported a global role for AnkB in maintenance of lens clarity, size, cytoarchitecture, and stiffness. Notably, absence of AnkB led to nuclear cataract formation, evident from P16. AnkB cKO lens fibers exhibit progressive disruption in membrane organization of the spectrin-actin cytoskeleton, channel proteins, cell-cell adhesion, shape change, loss and degradation of several membrane proteins (e.g., NrCAM. N-cadherin and aquaporin-0) along with a disorganized plasma membrane and impaired ball-and-socket membrane interdigitations. Furthermore, absence of AnkB led to decreased lens stiffness. Collectively, these results illustrate the essential role for AnkB in lens architecture, growth and function through its involvement in membrane protein and cytoskeletal organization.

Impact of Bariatric Surgery on Treatment Burden and Progression of Diabetic Retinopathy.

Purpose: To assess the severity, progression, and treatment burden of diabetic retinopathy (DR) in patients after bariatric surgery compared with controls. Methods: A retrospective cohort study was performed of patients with type 2 diabetes and DR seen at the Duke Eye Center between 2014 and 2023. Clinical data included hemoglobin A1c (HbA1c), diagnostic stage of DR, diabetic macular edema (DME) or vitreous hemorrhage (VH), visual acuity (VA), and treatment burden at baseline and follow-up. Generalized estimating equation analysis was used to account for the correlation between 2 eyes of the same patient. Results: Sixteen patients who had bariatric surgery were matched by age, sex, and duration of diabetes with 60 control patients managed medically during the same time period. The HbA1c level, severity of DR, presence of DME or VH, VA, and treatment burden were not significantly different (all P > .05) at the baseline examination. On average, patients were followed for 6 years. The HbA1c level at the follow-up was significantly lower in the bariatric surgery group (6.4% vs 8.5%; P < .001). At the follow-up, the treatment burden was reduced in the bariatric surgery group compared with the control group (P = .04). There was a clear trend toward reduced progression of DR and treatment burden in the bariatric surgery group over the follow-up. Conclusions: Bariatric surgery may improve glycemic control, stabilize DR progression, and reduce the treatment burden, which may have a significant impact on quality of life for patients with DR.

Evaluating the Impact of Gender, Race, and Training Year on Internal Medicine Residents' Experiences Across the United States.

INTRODUCTION: Prior studies have highlighted experiences of bias within resident training based on trainees' gender and race and high rates of burnout. However, few studies have addressed the intersection between bias and wellness for residents in internal medicine (IM) programs. This study explores how race, gender, and training year affect IM residents' bias experiences and well-being. METHODS: An anonymous survey with questions evaluating demographics and resident experiences of bias and perceptions of wellness and self-efficacy was distributed to 596 IM programs across the United States. Sixty-nine programs sent out the survey to their IM residents. Respondents to the survey included 176 residents. Descriptive analyses and χ2 tests were performed. RESULTS: Responses demonstrated that gender and race impacted residents' experiences with bias and misidentification. Eighty-eight percent of women compared to 1% of men, and 89% of Black residents compared to 3% of White residents reported being misidentified as a nonphysician due to gender and race, respectively. Degrees to which residents felt they were thriving in residency, experiencing burnout, and utilizing their strengths varied significantly by gender. Residents' self-perceived burnout levels were associated with being misidentified as not being a physician due to race. Experiences with bias also increased significantly with training year. DISCUSSION: This study provides important insights into the impact of gender, race/ethnicity, and training year on IM residents' experiences with bias and self-perception. CONCLUSION: The findings emphasize the need for structural changes within IM residency programs to reduce experiences of bias and to better cultivate the wellness of residents.

Evaluating the Impact of Gender and Race on Otolaryngology Resident Experiences Across the United States.

OBJECTIVE: Otolaryngology residents often encounter work-related stress and challenges during training. Sociodemographic factors influence experiences during residency; however, the impact of race and gender on otolaryngology trainee well-being during residency remains understudied. STUDY DESIGN: Online survey. SETTING: US residency programs. METHODS: An anonymous online survey consisting of 59 multiple-choice questions was sent to 104 directors of Accreditation Council for Graduate Medical Education otolaryngology residency programs to distribute to residents. Respondents were queried regarding demographics and experiences with bias. Residents self-identified gender and race. Black, Hispanic/Latinx, Middle Eastern/North African, and multiracial residents were categorized as underrepresented minorities (URM). RESULTS: Sixty-one US otolaryngology residents responded to the survey, the majority of whom were women (60.7%) and white (62%). Many residents endorsed a belief that receipt of research and training opportunities was negatively impacted by bias due to race (29.5%) or gender (45.9%). More women (27%) than men (13%) reported maximal burnout, and fewer men (17.4%) than women (40.5%) expressed low confidence in ability to independently care for patients. More male (47.8%) and white (31.6%) residents strongly agreed they were thriving. 94.6% of women and 33.3% of URM residents reported being mistaken for a nonphysician, compared to 0% of white male respondents. CONCLUSION: Otolaryngology residents perceived differential treatment based on race and gender, with women and URM residents experiencing greater exclusion and bias, as well as increased misidentification and decreased ability to thrive. Future work includes increasing sample size for generalizability and developing interventions that uphold equity in residency training environments.

Characterizing differences in retinal and choroidal microvasculature and structure in individuals with Huntington's Disease compared to healthy controls: A cross-sectional prospective study.

OBJECTIVE: To characterize retinal and choroidal microvascular and structural changes in patients who are gene positive for mutant huntingtin protein (mHtt) with symptoms of Huntington's Disease (HD). METHODS: This study is a cross-sectional comparison of patients who are gene positive for mHtt and exhibit symptoms of HD, either motor manifest or prodromal (HD group), and cognitively normal individuals without a family history of HD (control group). HD patients were diagnosed by Duke movement disorder neurologists based on the Unified Huntington's Disease Rating Scale (UHDRS). Fovea and optic nerve centered OCT and OCTA images were captured using Zeiss Cirrus HD-5000 with AngioPlex. Outcome metrics included central subfield thickness (CST), peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT, and foveal avascular zone (FAZ) area, vessel density (VD), perfusion density (PD), capillary perfusion density (CPD), and capillary flux index (CFI) on OCTA. Generalized estimating equation (GEE) models were used to account for inter-eye correlation. RESULTS: Forty-four eyes of 23 patients in the HD group and 77 eyes of 39 patients in the control group were analyzed. Average GCIPL thickness and FAZ area were decreased in the HD group compared to controls (p = 0.001, p < 0.001). No other imaging metrics were significantly different between groups. CONCLUSIONS: Patients in the HD group had decreased GCIPL thickness and smaller FAZ area, highlighting the potential use of retinal biomarkers in detecting neurodegenerative changes in HD.

Differences in Retinal and Choroidal Microvasculature and Structure in Dementia With Lewy Bodies Compared With Normal Cognition.

Purpose: To evaluate the retinal and choroidal microvasculature and structure in individuals with dementia with Lewy bodies (DLB) compared with controls with normal cognition using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: An institutional review board-approved cross-sectional comparison of patients with DLB and cognitively normal controls was performed. The Cirrus HD-OCT 5000 with AngioPlex (Carl Zeiss Meditec) was used to obtain OCT and OCTA images. Results: Thirty-four eyes of 18 patients with DLB and 85 eyes of 48 cognitively normal patients were analyzed. The average capillary perfusion density (CPD) was higher in the DLB group than in the control group (P = .005). The average capillary flux index (CFI) and ganglion cell inner-plexiform layer (GC-IPL) thickness were lower in the DLB group than in the control group (P = .016 and P = .040, respectively). Conclusions: Patients with DLB had an increased peripapillary CPD, decreased peripapillary CFI, and attenuated GC-IPL thickness compared with those with normal cognition.