Optometry Commons^™

Imbalanced Il-37/Tnf-Α/Ctss Signaling Disrupts Corneal Epithelial Barrier In A Dry Eye Model In Vitro, Yun Zhang, Jin-Miao Li, Rong Lu, Zhao Liu, Xin Chen, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

PURPOSE: To explore novel role and molecular mechanism of a natural anti-inflammatory cytokine interleukin (IL) 37 in preventing corneal epithelial barrier disruption from hyperosmolar stress as can occur in dry eye disease.

METHODS: Primary human corneal epithelial cells (HCECs) were cultured from fresh donor limbal explants. An in vitro dry eye model with hyperosmolar stress was established by switching HCECs from isosmolar (312mOsM) to hyperosmolar medium (350-500 mOsM), and some cells were treated with rhIL-37 or rhTNF-α, for different periods (2-48 h). The expression of cytokines and cathepsin S, and barrier protein integrity were evaluated by RT-qPCR, ELISA, and immunofluorescent …

Age Differential Response To Bevacizumab Therapy In Choroidal Neovascularization In Rabbits, Van Phuc Nguyen, Jessica Henry, Josh Zhe, Quynh Kieu, Wei Qian, Yingbin Fu, Xueding Wang, Yannis M Paulus

Faculty, Staff and Students Publications

Choroidal neovascularization (CNV) in young rabbits has been shown to have a rapid, robust response after treatment with bevacizumab, an anti-vascular endothelial growth factor (VEGF) medication. This investigation evaluates an age differential response to bevacizumab in older populations of rabbits using multimodal high resolution molecular imaging. Young (4 months old) and life span (14 months old) rabbits were given subretinal injections of Matrigel and VEGF to produce CNV. All CNV rabbit models were then treated with a bevacizumab intravitreal injection. Rabbits were then monitored longitudinally using photoacoustic microscopy (PAM), optical coherence tomography (OCT), color photography, and fluorescence imaging. Chain-like gold …

Mutations In Bcor, A Co-Repressor Of Crx/Otx2, Are Associated With Early-Onset Retinal Degeneration, Maéva Langouët, Christine Jolicoeur, Awais Javed, Pierre Mattar, Micah D Gearhart, Stephen P Daiger, Mette Bertelsen, Lisbeth Tranebjærg, Nanna D Rendtorff, Karen Grønskov, Catherine Jespersgaard, Rui Chen, Zixi Sun, Hui Li, Najmeh Alirezaie, Jacek Majewski, Vivian J Bardwell, Ruifang Sui, Robert K Koenekoop, Michel Cayouette

Faculty, Staff and Student Publications

Many transcription factors regulating the production, survival, and function of photoreceptor cells have been identified, but little is known about transcriptional co-regulators in retinal health and disease. Here, we show that BCL6 co-repressor (BCOR), a Polycomb repressive complex 1 factor mutated in various cancers, is involved in photoreceptor degenerative diseases. Using proteomics and transcription assays, we report that BCOR interacts with the transcription factors CRX and OTX2 and reduces their ability to activate the promoters of photoreceptor-specific genes. CUT&RUN sequencing further shows that BCOR shares genome-wide binding profiles with CRX/OTX2, consistent with a general co-repression activity. We also identify missense …

Surgical Extraction Of Traumatic Lodgment Of A Pen Nib Between The Eye And Nasal Bridge Of An Infant: A Case Report, Krishna Shah, Vaishali Prajapati, Smeet Desai, Karishma Dhaval Desai, Mayur B Wanjari, Deepika Singhal

Faculty, Staff and Students Publications

Unintentional eye injuries are common in small children. If left unobserved by parents or caretakers, it is challenging to assess as the kids are in distress and pain. Penetrating trauma in or near the eye requires urgent treatment as it can lead to infection and other complications. Early diagnosis and management help avoid further complications. An 11-month-old female was presented by her parents at a tertiary care clinic with inconsolable crying and swelling over the right eye's upper lid for one day. There was a history of possible trauma with a pen while the child was playing. During the examination, …

Immune Phenotype Of The Cd4+ T Cells In The Aged Lymphoid Organs And Lacrimal Glands, Claudia M Trujillo-Vargas, Kelsey E Mauk, Humberto Hernandez, Rodrigo G De Souza, Zhiyuan Yu, Jeremias G Galletti, Jana Dietrich, Friedrich Paulsen, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) in lymphoid organs from female C57BL/6J mice and subjected these cells to an immunology NanoString® panel. These results were confirmed by flow cytometry, live imaging, and tissue immunostaining in the lacrimal gland. Importantly, effector T helper 1 (Th1) genes were highly upregulated on aged Tregs, including the master regulator Tbx21. Among …

Effect Of The Covid-19 Pandemic Lockdown On The Management Of Diabetic Retinopathy: A Cross-Sectional Study, Vaishali Prajapati, Krishna Shah, Dhruvi Shah, Mayur B Wanjari, Deepika Singhal

Faculty, Staff and Students Publications

Introduction Worldwide, diabetic retinopathy (DR) is one of the leading causes of vision loss. Early treatment and screening for DR have a major role in reducing the rate of the disease and the coronavirus disease 2019 (COVID-19) pandemic-related restrictions have altered real-world practice patterns in managing DR. Aims and objectives To evaluate the impact of the COVID-19 pandemic on the management of DR amongst patients presenting to a tertiary eye care center in Gujarat, India. Methods This is a cross-sectional study comparison of ophthalmic findings of 72 patients who presented to a tertiary care hospital with the manifestation of DR …

Paclitaxel And Urolithin A Prevent Histamine-Induced Neurovascular Breakdown Alike, In An, Srijayaprakash Uppada, Dianxiong Zou, Erin M Scott, Gladys Ko, Stephen Pflugfelder, M N V Ravi Kumar, Raghu Ganugula

Faculty, Staff and Students Publications

Neurovascular eye problems are better prevented than managed or treated. Despite growing concern of occurrence in aging populations and development secondary to diseases such as diabetes and hypertension, we currently have very few options to tackle this global problem. Creating effective and high-throughput screening strategies is as important as the intervention itself. Here, we present for the first time a robust ex vivo rat eye model of histamine-induced vascular damage for investigating the therapeutic potential of paclitaxel (PTX) and urolithin A (UA) as alternatives to dexamethasone for preventing vascular damage in the retina. Extensive loss of vascularization and apoptosis were …

Impact Of Coronavirus Disease 2019 Restrictions On Retinal Detachment: A Multicenter Experience, Jesse J Jung, Jonathan S Chang, Patrick R Oellers, Mohsin H Ali, Brian K Do, Joseph J Tseng, Roberto Roizenblatt, Rajeev H Muni, Christina Y Weng, Zackery B Oakey, Sean W Tsao, Soraya Rofagha, Xavier Chan, Quan V Hoang

Faculty, Staff and Students Publications

In this retrospective, multicenter study of 261 eyes (259 patients), patients who underwent rhegmatogenous retinal detachment repair during the coronavirus disease 2019 (COVID-19) post-lockdown period experienced an additional 22-day delay, leading to significantly more epiretinal membrane and proliferative vitreoretinopathy and lower single-surgery anatomic success rates. During lockdown, perfluoropropane gas was used more commonly, and pneumatic retinopexy was used more commonly in COVID-19-positive patients.

Divergent Outer Retinal Circuits Drive Image And Non-Image Visual Behaviors, Corinne Beier, Ulisse Bocchero, Lior Levy, Zhijing Zhang, Nange Jin, Stephen C Massey, Christophe P Ribelayga, Kirill Martemyanov, Samer Hattar, Johan Pahlberg

Faculty, Staff and Student Publications

Image- and non-image-forming vision are essential for animal behavior. Here we use genetically modified mouse lines to examine retinal circuits driving image- and non-image-functions. We describe the outer retinal circuits underlying the pupillary light response (PLR) and circadian photoentrainment, two non-image-forming behaviors. Rods and cones signal light increments and decrements through the ON and OFF pathways, respectively. We find that the OFF pathway drives image-forming vision but cannot drive circadian photoentrainment or the PLR. Cone light responses drive image formation but fail to drive the PLR. At photopic levels, rods use the primary and secondary rod pathways to drive the …

An Introduction To Biosimilars For The Treatment Of Retinal Diseases: A Narrative Review, Seenu M Hariprasad, Richard P Gale, Christina Y Weng, Hans C Ebbers, Mourad F Rezk, Ramin Tadayoni

Faculty, Staff and Students Publications

Biological therapies have revolutionized the treatment of disease across a number of therapeutic areas including retinal diseases. However, on occasion, such treatments may be relatively more expensive compared to small molecule therapies. This can restrict patient access and treatment length leading to suboptimal clinical outcomes. Several biosimilar candidates of ranibizumab and aflibercept are currently in development and the first biosimilar of ranibizumab received EMA approval in August and FDA approval in September 2021. Biosimilars are biological medicines that are highly similar to an already-approved biological medicine (reference product). The physicochemical and clinical similarity of a biosimilar is determined by a …

Neurovascular Abnormalities In Retinopathy Of Prematurity And Emerging Therapies, Chang Dai, Jun Xiao, Chenguang Wang, Wei Li, Guanfang Su

Faculty, Staff and Students Publications

Blood vessels in the developing retina are formed in concert with neural growth, resulting in functional neurovascular network. Disruption of the neurovascular coordination contributes to the pathogenesis of retinopathy of prematurity (ROP), a potentially blinding retinal neovascular disease in preterm infants that currently lacks an approved drug therapy in the USA. Despite vasculopathy as predominant clinical manifestations, an increasing number of studies revealed complex neurovascular interplays among neurons, glial cells and blood vessels during ROP. Coordinated expression of glia-derived vascular endothelial growth factor (VEGF) in spatio-temporal gradients is pivotal to the formation of well-organized vascular plexuses in the healthy retina, …

Persistent Opioid Use In Cataract Surgery Pain Management And The Role Of Nonopioid Alternatives, Richard S Davidson, Kendall Donaldson, Maggie Jeffries, Sumitra Khandelwal, Michael Raizman, Yasaira Rodriguez Torres, Terry Kim

Faculty, Staff and Students Publications

Cataracts are a leading cause of preventable blindness globally. Although care varies between developing and industrialized countries, surgery is the single effective approach to treating cataracts. From the earliest documented primitive cataract removals to today's advanced techniques, cataract surgery has evolved dramatically. As surgical techniques have developed, so have approaches to surgical pain management. With current cataract surgical procedures and advanced technology, anesthesia and intraoperative pain management have shifted to topical/intracameral anesthetics, with or without low-dose systemic analgesia and anxiolysis. Despite this, pain and discomfort persist in some patients and are underappreciated in modern cataract surgery. Although pain management has …

Comparative Ligandomics Implicates Secretogranin Iii As A Disease-Restricted Angiogenic Factor In Laser-Induced Choroidal Neovascularization, Liyang Ji, Prabuddha Waduge, Wencui Wan, Hong Tian, Jin Li, Jinsong Zhang, Rui Chen, Wei Li

Faculty, Staff and Students Publications

Choroidal neovascularization (CNV) is a leading cause of vision loss in the elderly. All approved anti-angiogenic drug therapies for CNV target vascular endothelial growth factor (VEGF) but confer limited efficacy. Identification of other CNV-related angiogenic factors will facilitate the development of VEGF-independent alternative therapies. Here, we applied comparative ligandomics to live mice with or without laser-induced CNV for global mapping of CNV-selective endothelial ligands. Secretogranin III (Scg3) previously identified by the same approach as a diabetes-restricted angiogenic factor was mapped with more than 935-fold increase in binding to CNV vessels compared to healthy choriocapillaris. A novel in vivo ligand binding …

Impact Of The Covid-19 Pandemic On Visual Outcomes Of Diabetic Macular Edema Patients At A Tertiary Care Veterans Affairs Center, Philip Zhou, Jie Gao, Xiaofan Huang, Kristen A Staggers, Kristin Biggerstaff, Silvia Orengo-Nania, Roomasa Channa

Faculty, Staff and Students Publications

PURPOSE: There are limited studies on factors that impacted retina clinic patient outcomes during the COVID-19 pandemic. We aimed to evaluate visual and anatomic outcomes in patients with diabetic macular edema (DME) requiring anti-VEGF injections at the veterans' affairs tertiary care eye clinic in Houston, TX.

METHODS: Patient volume from April 2020 was compared to that of April 2019 to determine attendance changes. To evaluate outcomes, we reviewed patients with DME who had scheduled appointments during April 2020. We tracked changes in central foveal thickness (CFT) and Snellen visual acuity (VA) measurements. Patient outcomes were classified as poor (defined as …

Mucosal Immunology Of The Ocular Surface, Cintia S De Paiva, Anthony J St Leger, Rachel R Caspi

Faculty, Staff and Students Publications

The eye is a sensory organ exposed to the environment and protected by a mucosal tissue barrier. While it shares a number of features with other mucosal tissues, the ocular mucosal system, composed of the conjunctiva, Meibomian glands, and lacrimal glands, is specialized to address the unique needs of (a) lubrication and (b) host defense of the ocular surface. Not surprisingly, most challenges, physical and immunological, to the homeostasis of the eye fall into those two categories. Dry eye, a dysfunction of the lacrimal glands and/or Meibomian glands, which can both cause, or arise from, sensory defects, including those caused …

Bacteroides Ovatus Colonization Influences The Abundance Of Intestinal Short Chain Fatty Acids And Neurotransmitters, Thomas D Horvath, Faith D Ihekweazu, Sigmund J Haidacher, Wenly Ruan, Kristen A Engevik, Robert Fultz, Kathleen M Hoch, Ruth Ann Luna, Numan Oezguen, Jennifer K Spinler, Anthony M Haag, James Versalovic, Melinda A Engevik

Faculty, Staff and Students Publications

Gut microbes can synthesize multiple neuro-active metabolites. We profiled neuro-active compounds produced by the gut commensal Bacteroides ovatus in vitro and in vivo by LC-MS/MS. We found that B. ovatus generates acetic acid, propionic acid, isobutyric acid, and isovaleric acid. In vitro, B. ovatus consumed tryptophan and glutamate and synthesized the neuro-active compounds glutamine and GABA. Consistent with our LC-MS/MS-based in vitro data, we observed elevated levels of acetic acid, propionic acid, isobutyric acid, and isovaleric acid in the intestines of B. ovatus mono-associated mice compared with germ-free controls. B. ovatus mono-association also increased the concentrations of intestinal GABA …

Safety And Efficacy Of Systemic Anti-Scg3 Therapy To Treat Oxygen-Induced Retinopathy, Chang Dai, Hong Tian, Amit Bhatt, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

BACKGROUND: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim …

Safety And Efficacy Of Systemic Anti-Scg3 Therapy To Treat Oxygen-Induced Retinopathy, Chang Dai, Hong Tian, Amit Bhatt, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

BACKGROUND: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim …

Clinical Presentation, Treatment, And Genetic And Histopathological Analysis Of Juvenile Cataracts And Secondary Glaucoma In A Rhesus Macaque (Macaca Mulatta), M Isabel Casanova, Rui Chen, Laura M Garzel, Katherine J Olstad, Soohyun Kim, Ronald Alan Harris, Yumei Li, Muthuswamy Raveendran, Qingnan Liang, Jun Wang, Glenn Yiu, John Timothy Stout, Jeffrey A Roberts, Jeffrey Rogers, Ala Moshiri, Sara M Thomasy

Faculty, Staff and Students Publications

This report describes the clinical and histological findings, genetic study, and treatment in a 1.3-year-old rhesus macaque with bilateral cataracts and unilateral secondary glaucoma. Intravitreal injection of gentamicin decreased the intraocular pressure from 56 to <2 mm Hg. A putative genetic cause of the cataracts was not identified.

Single-Cell Transcriptional Profiling Of Murine Conjunctival Immune Cells Reveals Distinct Populations Expressing Homeostatic And Regulatory Genes, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Immune cells in the exposed conjunctiva mucosa defend against environmental and microbial stresses. Expression profiling by single-cell RNA sequencing was performed to identify conjunctival immune cell populations expressing homeostatic and regulatory genes. Fourteen distinct clusters were identified, including myeloid cells (neutrophils, monocytes, macrophages), dendritic cells (DC), and lymphoid cells (B, T, γδT, ILC2, and NK) lineages. Novel neutrophil [lipocalin (Lcn2) high and low), and MHCIIlo macrophage (MP) clusters were identified. More than half of the cells map to myeloid and dendritic cell populations with differential expression profiles that include genes with homeostatic and regulatory functions: Serpinb2 (MHCIIlo macrophage), …

Retinal Organoids Derived From Rhesus Macaque Ipscs Undergo Accelerated Differentiation Compared To Human Stem Cells, Antonio Jacobo Lopez, Sangbae Kim, Xinye Qian, Jeffrey Rogers, J Timothy Stout, Sara M Thomasy, Anna La Torre, Rui Chen, Ala Moshiri

Faculty, Staff and Students Publications

PURPOSE: To compare the timing and efficiency of the development of Macaca mulatta, a nonhuman primate (NHP), induced pluripotent stem cell (rhiPSC) derived retinal organoids to those derived from human embryonic stem cells (hESCs).

RESULTS: Generation of retinal organoids was achieved from both human and several NHP pluripotent stem cell lines. All rhiPSC lines resulted in retinal differentiation with the formation of optic vesicle-like structures similar to what has been observed in hESC retinal organoids. NHP retinal organoids had laminated structure and were composed of mature retinal cell types including cone and rod photoreceptors. Single-cell RNA sequencing was conducted at …

Gut-Derived Butyrate Suppresses Ocular Surface Inflammation, Laura Schaefer, Humberto Hernandez, Rosalind A Coats, Zhiyuan Yu, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Dry eye is a common ocular inflammatory disorder characterized by tear film instability and reduced tear production. There is increasing evidence that homeostasis of the ocular surface is impacted by the intestinal microbiome. We are interested in investigating the potential role of microbially produced small molecules in mediating the interaction between the intestinal microbiota and the ocular surface. One such molecule is butyrate, a short-chain fatty acid (SCFA) produced by certain members of the gut microbiota through fermentation of dietary fiber. Here we show that SCFA transporter SLC5A8 is expressed in vivo in murine conjunctival and corneal epithelium. Pre-treatment of …

Exaggerated False Positives By Popular Differential Expression Methods When Analyzing Human Population Samples, Yumei Li, Xinzhou Ge, Fanglue Peng, Wei Li, Jingyi Jessica Li

Faculty, Staff and Students Publications

When identifying differentially expressed genes between two conditions using human population RNA-seq samples, we found a phenomenon by permutation analysis: two popular bioinformatics methods, DESeq2 and edgeR, have unexpectedly high false discovery rates. Expanding the analysis to limma-voom, NOISeq, dearseq, and Wilcoxon rank-sum test, we found that FDR control is often failed except for the Wilcoxon rank-sum test. Particularly, the actual FDRs of DESeq2 and edgeR sometimes exceed 20% when the target FDR is 5%. Based on these results, for population-level RNA-seq studies with large sample sizes, we recommend the Wilcoxon rank-sum test.

Genetic Subtyping And Phenotypic Characterization Of The Immune Microenvironment And Myc/Bcl2 Double Expression Reveal Heterogeneity In Diffuse Large B-Cell Lymphoma, Zijun Y Xu-Monette, Li Wei, Xiaosheng Fang, Qingyan Au, Harry Nunns, Máté Nagy, Alexandar Tzankov, Feng Zhu, Carlo Visco, Govind Bhagat, Karen Dybkaer, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Fredrick B Hagemeister, Xiaoping Sun, Xin Han, Heounjeong Go, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Benjamin M Parsons, J Han Van Krieken, Miguel A Piris, Jane N Winter, Yong Li, Bing Xu, Maher Albitar, Hua You, Ken H Young

Faculty, Staff and Students Publications

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is molecularly and clinically heterogeneous, and can be subtyped according to genetic alterations, cell-of-origin, or microenvironmental signatures using high-throughput genomic data at the DNA or RNA level. Although high-throughput proteomic profiling has not been available for DLBCL subtyping, MYC/BCL2 protein double expression (DE) is an established prognostic biomarker in DLBCL. The purpose of this study is to reveal the relative prognostic roles of DLBCL genetic, phenotypic, and microenvironmental biomarkers.

EXPERIMENTAL DESIGN: We performed targeted next-generation sequencing; IHC for MYC, BCL2, and FN1; and fluorescent multiplex IHC for microenvironmental markers in a large cohort of …

Visual Pigment-Deficient Cones Survive And Mediate Visual Signaling Despite The Lack Of Outer Segments, Hui Xu, Nange Jin, Jen-Zen Chuang, Zhao Zhang, Xiaoyue Zhong, Zhijing Zhang, Ching-Hwa Sung, Christophe P Ribelayga, Yingbin Fu

Faculty, Staff and Students Publications

Rhodopsin and cone opsins are essential for light detection in vertebrate rods and cones, respectively. It is well established that rhodopsin is required for rod phototransduction, outer segment disk morphogenesis, and rod viability. However, the roles of cone opsins are less well understood. In this study, we adopted a loss-of-function approach to investigate the physiological roles of cone opsins in mice. We showed that cones lacking cone opsins do not form normal outer segments due to the lack of disk morphogenesis. Surprisingly, cone opsin-deficient cones survive for at least 12 mo, which is in stark contrast to the rapid rod …

Abnormal Perception Of Pattern-Induced Flicker Colors In Subjects With Glaucoma, Padmapriya Ramamoorthy, Nicole L Alexander, Benjamin J Frankfort

Faculty, Staff and Students Publications

Pattern-induced flicker colors (PIFCs) are subjective colors that can be elicited with rotation of an achromatic stimulus such as the Benham disk. The perceptive mechanisms underlying PIFCs are not well-understood, but are thought to be generated primarily by retinal cell types which may be dysfunctional in glaucoma. Using a custom computer-based system, we tested PIFC perception across several Benham disk parameters, including the rates of acceleration and deceleration, rotational direction, and image contrast in both control and glaucoma subjects. We defined the Benham perception limit (BPL) during acceleration as the rotational speed at which PIFCs were first detected (Benham perception …

Review Of Gene Therapies For Age-Related Macular Degeneration, Arshad M Khanani, Mathew J Thomas, Aamir A Aziz, Christina Y Weng, Carl J Danzig, Glenn Yiu, Szilárd Kiss, Nadia K Waheed, Peter K Kaiser

Faculty, Staff and Students Publications

Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for …

Progressive, Long-Term Hearing Loss In Congenital Cmv Disease After Ganciclovir Therapy, Tatiana M Lanzieri, Alison Chantal Caviness, Peggy Blum, Gail Demmler-Harrison

Faculty, Staff and Students Publications

BACKGROUND: Long-term hearing outcomes among children with symptomatic congenital cytomegalovirus (CMV) disease who received 6-week ganciclovir therapy early in life are unknown.

METHODS: Longitudinal study of 76 children with symptomatic congenital CMV disease, born 1983-2005, who were categorized into three groups: group A treated with ganciclovir; group B untreated who had microcephaly, chorioretinitis, or sensorineural hearing loss (SNHL; ≥25 dB) diagnosed in the first month of life (congenital); and group C untreated who did not meet criteria for group B.

RESULTS: Patients in groups A (n = 17), B (n = 27), and C (n = 32) were followed to …

Secretogranin Iii Stringently Regulates Pathological But Not Physiological Angiogenesis In Oxygen-Induced Retinopathy, Chang Dai, Prabuddha Waduge, Liyang Ji, Chengchi Huang, Ye He, Hong Tian, Elizabeth Zuniga-Sanchez, Amit Bhatt, Iok-Hou Pang, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Conventional angiogenic factors, such as vascular endothelial growth factor (VEGF), regulate both pathological and physiological angiogenesis indiscriminately, and their inhibitors may elicit adverse side effects. Secretogranin III (Scg3) was recently reported to be a diabetes-restricted VEGF-independent angiogenic factor, but the disease selectivity of Scg3 in retinopathy of prematurity (ROP), a retinal disease in preterm infants with concurrent pathological and physiological angiogenesis, was not defined. Here, using oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, we quantified an exclusive binding of Scg3 to diseased versus healthy developing neovessels that contrasted sharply with the ubiquitous binding of VEGF. Functional immunohistochemistry visualized …

3’Aqtl-Atlas: An Atlas Of 3’Utr Alternative Polyadenylation Quantitative Trait Loci Across Human Normal Tissues, Ya Cui, Fanglue Peng, Dan Wang, Yumei Li, Jason Sheng Li, Lei Li, Wei Li

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) have identified thousands of non-coding single-nucleotide polymorphisms (SNPs) associated with human traits and diseases. However, functional interpretation of these SNPs remains a significant challenge. Our recent study established the concept of 3' untranslated region (3'UTR) alternative polyadenylation (APA) quantitative trait loci (3'aQTLs), which can be used to interpret ∼16.1% of GWAS SNPs and are distinct from gene expression QTLs and splicing QTLs. Despite the growing interest in 3'aQTLs, there is no comprehensive database for users to search and visualize them across human normal tissues. In the 3'aQTL-atlas (https://wlcb.oit.uci.edu/3aQTLatlas), we provide a comprehensive list of 3'aQTLs containing …