Eye Diseases Commons^™

Yap1-Dependent Regulation Of Cell Size In Bcam-Positive Limbal Corneal Progenitor Cells, Kosei Suzuki, Shinri Sato, Markus H. Frank, Natasha Y. Frank, Yuzuru Sasamoto

Research outputs 2022 to 2026

Cell size has been associated with stem and progenitor cell states across multiple tissues, yet its regulation in the human corneal epithelium remains incompletely understood. This study aimed to characterize cell-size differences among limbal and corneal epithelial cell populations defined by the limbal stem cell (LSC) marker ABCB5 and the transit-amplifying cell (TAC) marker BCAM, and to investigate the molecular regulators of progenitor cell size. ABCB5-positive LSCs and BCAM-positive TACs were identified and isolated by flow cytometry, and the mean cell size was estimated using forward scatter (FSC). As a result, ABCB5-positive LSCs were significantly smaller than ABCB5-negative limbal epithelial …

Inpatient Versus Outpatient Management Of Bilateral Optic Nerve Head Elevation Presentation To A Tertiary Emergency Department, Mengchen Suo, Johnny Lo, Fred K. Chen

Research outputs 2022 to 2026

Introduction: Increased accessibility to fundus cameras has changed the referral pattern for patients with suspected bilateral optic nerve head elevation (BONHE) presenting to emergency departments (EDs). We aim to review the management of these patients to streamline the process. Methods: A retrospective review of patients with suspected BONHE referred to a tertiary centre ED between 2017 and 2022. We collected demographics, referral source, clinical assessment, neuroimaging and retinal imaging results. Final diagnosis and treatment outcomes were compared between those managed as inpatients and those managed as outpatients. Results: 100 patients were referred to the ED with a suspected BONHE. Most …

Abca4 Versus Prph2-Associated Retinopathy: Clinical And Electrophysiological Findings, Rachael C. Heath Jeffery, A. Thompson, Johnny Lo, Andrea L. Vincent, Minal Patil, Lorenzo Bianco, Maurizio Battaglia Parodi, Lucia Ziccardi, Carmen Dell’Aquila, Lucilla Barbano, Wei Chao Tang, Choi Mun Chan, Camiel J.F. Boon, Jonathan Hensman, Ta Ching Chen, Chien Yu Lin, Pei Lung Chen, Ajoy Vincent, Anupreet Tumber, Elise Heon, John R. Grigg, Robyn V. Jamieson, Elisa E. Cornish, Benjamin N. Nash, Jeremy Chou, Tina M. Lamey

Research outputs 2022 to 2026

Purpose. The purpose of this study was to characterize the clinical features, electrophysiology, and variant spectrum in ABCA4- and PRPH2-retinopathies and to identify novel electrodiagnostic biomarkers to differentiate between these two genotypes. Methods. We conducted an international multicenter case-control study of patients with a clinical and genetic diagnosis of ABCA4- or PRPH2-retinopathy. Age at symptom onset, best-corrected visual acuity (BCVA), electroretinography (ERG) components, and fundus autofluorescence (FAF) imaging were compared. Subgroup exploratory analysis was performed on those patients with a phenotype similar to central areolar choroidal dystrophy (“CACD-like”), those with flecks distributed throughout the posterior pole (“fleck-like”) and a healthy …

Essential Role Of Cd63 In Maintaining Corneal Epithelial Identity In The Human Limbus, Yuzuru Sasamoto, Kosei Suzuki, Shinri Sato, Catherine A.A. Lee, Gabrielle Martin, Bruce R. Ksander, Markus H. Frank, Natasha Y. Frank

Research outputs 2022 to 2026

Purpose: Building on the identification of ABCB5 as a marker of limbal stem cells (LSCs), this study examines CD63, a newly identified molecule co-expressed with ABCB5 in limbal epithelial cells, to define its role in maintaining corneal epithelial cell identity. Methods: RNA sequencing (RNA-seq) was performed on flow cytometry–sorted Abcb5-positive and Abcb5-negative murine corneal epithelial cells. CD63 expression in human corneal tissue was assessed by immunostaining. CD63 was silenced in cultured human limbal epithelial cells using siRNA-mediated knockdown and resulting molecular and cellular changes were analyzed by qRT-PCR, flow cytometry, RNA-seq, Western blotting, and cell proliferation assays. Results: RNA-seq analysis …

Myeov Is A Novel Marker Of Differentiated Corneal Epithelium, Yoshiko Fukuda, Chao Zhang, Bruce R. Ksander, Vickie Y. Jo, Christine G. Lian, George F. Murphy, Markus H. Frank, Natasha Y. Frank, Yuzuru Sasamoto

Research outputs 2022 to 2026

Purpose. Myeloma overexpressed gene (MYEOV) was initially identified as a gene amplified in several malignancies and was found to promote cell proliferation and metastasis. Our previous comparative RNA sequencing and epigenetic analyses revealed high MYEOV levels in differentiated corneal epithelial cells and showed that TET2 epigenetically regulated MYEOV expression. In the current study, we aimed to further characterize the expression and regulation of MYEOV in the human ocular surface. Methods. MYEOV expression was examined by immunostaining of the human corneas and by analysis of the publicly available single-cell RNA sequencing data. Gene knockdown (KD) of MYEOV and the regulators of …

Metabolomic-Derived Endotypes Of Age-Related Macular Degeneration (Amd): A Step Towards Identification Of Disease Subgroups, Kevin Mendez, Ines Lains, Rachel S. Kelly, João Gil, Rufino Silva, John Miller, Demetrios G. Vavvas, Ivana Kim, Joan Miller, Liming Liang, Jessica A. Lasky-Su, Deeba Husain

Research outputs 2022 to 2026

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a complex pathophysiology and phenotypic diversity. Here, we apply Similarity Network Fusion (SNF) to cluster AMD patients into putative metabolomics-derived endotypes. Using a discovery cohort of 163 AMD patients from Boston, US, and a validation cohort of 214 patients from Coimbra, Portugal, we identified four distinct metabolomics-derived endotypes with varying retinal structural and functional characteristics, confirmed across both cohorts. Patients clustered into Endotype 1 exhibited a milder form of AMD and were characterized by low levels of amino acids in specific metabolic pathways. Meanwhile, patients clustered into both …

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum And Novel Clinical Observations In 241 Patients, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Enid S. Chelva, Sean Armstrong, Jose S. Pulido, Rebecca Procopio, Andrea L. Vincent, Lorenzo Bianco, Maurizio Battaglia Parodi, Lucia Ziccardi, Giulio Antonelli, Lucilla Barbano, João P. Marques, Sara Geada, Ana L. Carvalho, Wei C. Tang, Choi M. Chan, Camiel J.F. Boon, Jonathan Hensman, Ta Ching Chen, Chien Yu Lin, Pei Lung Chen, Ajoy Vincent, Anupreet Tumber, Elise Heon

Research outputs 2022 to 2026

Purpose:

To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

Methods.

A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype–phenotype correlations.

Results:

The median age at symptom onset was 40 years (range, 4–78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, …

Abcb5+ Limbal Epithelial Stem Cells Inhibit Developmental But Promote Inflammatory (Lymph) Angiogenesis While Preventing Corneal Inflammation, Berbang Meshko, Thomas L. A. Volatier, Karina Hadrian, Shuya Deng, Yanhong Hou, Mark A. Kluth, Christoph Ganss, Markus H. Frank, Natasha Y. Frank, Bruce Ksander, Claus Cursiefen, Maria Notara

Research outputs 2022 to 2026

The limbus, the vascularized junction between the cornea and conjunctiva, is thought to function as a barrier against corneal neovascularization. However, the exact mechanisms regulating this remain unknown. In this study, the limbal epithelial stem cell (LESC) marker ABCB5 was used to investigate the role of LESCs in corneal neovascularization. In an ABCB5KO model, a mild but significant increase of limbal lymphatic and blood vascular network complexity was observed in developing mice (4 weeks) but not in adult mice. Conversely, when using a cornea suture model, the WT animals exhibited a mild but significant increase in the number of lymphatic …

Incidence And Mortality Of Conjunctival Melanoma In Australia (1982 To 2014), Aaron B. Beasley, David B. Preen, Samuel Mclenachan, Elin S. Gray, Fred K. Chen

Research outputs 2022 to 2026

Purpose: The purpose of this study was to estimate the incidence and mortality of conjunctival melanoma in Australia from 1982 to 2014. Methods: De-identified unit data for all cases of ocular melanoma were extracted from the Australian Cancer Database from 1982 to 2014. Conjunctival melanoma cases were extracted, and the incidence and mortality were analyzed. Incidence rates were age-standardized against the 2001 Australian Standard Population. Mortality was assessed using log-rank and Cox regression. Results: From 1982 to 2014, there were 299 cases of conjunctival melanoma. The age-standardized incidence rate was 0.48 (95% confidence interval [CI] = 0.41 to 0.54) per …

Driving With Retinitis Pigmentosa, Rachael C. Heath Jeffery, Johnny Lo, Jennifer A. Thompson, Tina M. Lamey, Terri L. Mclaren, John N. Deroach, Miguel S. Kabilio, Fred K. Chen

Research outputs 2022 to 2026

Background: To establish the proportion of patients with retinitis pigmentosa (RP) meeting the Australian fitness to drive (FTD) visual standards. Methodology: A prospective consecutive case series of patients with a clinical or genetic diagnosis of RP. Data on age at symptom onset, current driving status, inheritance pattern, better eye visual acuity (BEVA), binocular Esterman visual field (BEVF) parameters, genotype and ability to meet the driving standards based on BEVA and BEVF were collected. Outcome measures included the proportion of RP patients overall meeting the standards and clinical predictors for passing. A sub-analysis was performed on those RP patients who reported …

Facial Dermatosis Papulosa Nigra, A Risk For The Development Of Pterygium And Myopia: A Descriptive Cross-Sectional Study In Ghana, Du Bois Asante, Korantema M. Tsegah, Ebenezer Afrifa-Yamoah, Samuel Kyei, Dunyah J. Dzidzor, Reindolf Anokye

Research outputs 2022 to 2026

Background: Dermatosis papulosa nigra (DPN) affects sun-exposed areas such as the face, neck, and trunk. The prevalence of pterygium and myopia in DPN patients in Ghana has not been studied. In this study, we examined the risk and protective factors for pterygium and myopia in DPN patients. Materials and Methods: The study involved 100 participants with facial DPN. A standard ophthalmic exam was performed using a portable slit lamp and a 3.5 X magnified loop. Participants completed a closed-ended questionnaire. Logistic regression was used to summarize the level of association between DPN, myopia, and pterygium, as well as demographic factors …

Anti-Retinal Igg Antibodies In Patients With Early And Advanced Type 2 Macular Telangiectasia, Samuel Mclenachan, Chandrakumar Balaratnasingam, Rachael C. Heath Jeffery, Shang Chih Chen, Dan Zhang, Geoffrey Chan, Rosa Dolz-Marco, Tommaso Bacci, Johnny Lo, Steven Wiffen, Lawrence A. Yannuzzi, Fred K. Chen

Research outputs 2022 to 2026

Type 2 idiopathic macular telangiectasia (MacTel-2) is a progressive adult-onset macular disease associated with bilateral perifoveal vascular changes, Muller cell degeneration and increased blood-retinal barrier permeability. The pathophysiological mechanisms of MacTel-2 remain unclear, however it was previously reported that anti-retinal antibodies in MacTel-2 patients are a significant feature of the disease. In this study, we aimed to compare the prevalence of anti-retinal antibodies in patients MacTel-2, healthy controls and patients with other retinal diseases. MacTel-2 patients diagnosed with multimodal imaging were enrolled and their disease severities were graded using spectral-domain optical coherence tomography. For comparison, patients with age-related macular degeneration …

Sibling Concordance In Symptom Onset And Atrophy Growth Rates In Stargardt Disease Using Ultra-Widefield Fundus Autofluorescence, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Tina M. Lamey, Terri L. Mclaren, John N. De Roach, Dimitar N. Azamanov, Ian L. Mcallister, Ian J. Constable, Fred K. Chen

Research outputs 2022 to 2026

Purpose: To investigate concordance in symptom onset, area of dark autofluorescence (DAF), and growth rate (GR) between Stargardt disease siblings at an age-matched time point. Methods: In this retrospective longitudinal study of sibling pairs with identical biallelic ABCA4 variants, age at symptom onset, best-corrected visual acuity, atrophy area, and effective radius of DAF on ultra-widefield fundus autofluorescence were recorded. Absolute intersibling differences for both eyes were compared with absolute interocular differences using the Mann-Whitney test. Results: Overall 39 patients from 19 families were recruited. In 16 families, age-matched best-corrected visual acuity and DAF were compared between siblings. In 8 families, …

Age-Related Neurodegenerative Disease Associated Pathways Identified In Retinal And Vitreous Proteome From Human Glaucoma Eyes, M. Mirzaei, Veer Bala Gupta, J. M. Chick, T. M. Greco, Y. Wu, N. Chitranshi, R. V. Wall, Eugene Hone, L. Deng, Y. Dheer, M. Abbasi, M. Rezaeian, N. Braidy, Y. You, G. H. Salekdeh, P. A. Haynes, M. P. Molloy, Ralph Martins, I. M. Cristea, S. P. Gygi, S. L. Graham, V. K. Gupta

Research outputs 2014 to 2021

Glaucoma is a chronic disease that shares many similarities with other neurodegenerative disorders of the central nervous system. This study was designed to evaluate the association between glaucoma and other neurodegenerative disorders by investigating glaucoma-associated protein changes in the retina and vitreous humour. The multiplexed Tandem Mass Tag based proteomics (TMT-MS3) was carried out on retinal tissue and vitreous humour fluid collected from glaucoma patients and age-matched controls followed by functional pathway and protein network interaction analysis. About 5000 proteins were quantified from retinal tissue and vitreous fluid of glaucoma and control eyes. Of the differentially regulated proteins, 122 were …