Publications by authors named "Joseph Ryu"

Protein phosphatase 2 regulatory subunit B56δ related neurodevelopmental disorder (PPP2R5D-related NDD) is largely caused by de novo heterozygous missense PPP2R5D variants. We report medical characteristics, longitudinal adaptive functioning, and in-person neurological, motor, cognitive, and electroencephalogram (EEG) activity for PPP2R5D-related NDD. Forty-two individuals (median age 6 years, range = 0.

View Article and Find Full Text PDF

A specific targeting nuclease is a powerful tool for mediating genome alternative expression with high precision. The RNA sequence-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system can be used to facilitate genome engineering in cells by using a 20-nt targeting sequence. In this chapter, we describe a set of tools for Cas9-mediated genome editing via non-homologous end joining (NHEJ) or homology-directed repair (HDR) in the generation of modified cell lines for downstream functional studies.

View Article and Find Full Text PDF

The development of fundus photography and imaging has improved our ability to diagnose and monitor inherited retinal degenerations. Nowadays, color fundus photography has become a staple in evaluating patients with retinitis pigmentosa (RP). Other important multimodal forms of fundus photography used today include red-free fundus photography, short-wavelength autofluorescence, and near-infrared autofluorescence.

View Article and Find Full Text PDF

Background: Inherited retinal dystrophies describe a heterogeneous group of retinal diseases that lead to the irreversible degeneration of rod and cone photoreceptors and eventual blindness. Recessive loss-of-function mutations in Tubulin Tyrosine Ligase Like 5 (TTLL5) represent a recently described cause of inherited cone-rod and cone dystrophy. This study describes the unusual phenotypes of three patients with autosomal recessive mutations in TTLL5.

View Article and Find Full Text PDF

Mutations in rhodopsin (RHO) are the most common causes of autosomal dominant retinitis pigmentosa (adRP), accounting for 20% to 30% of all cases worldwide. However, the high degree of genetic heterogeneity makes development of effective therapies cumbersome. To provide a universal solution to RHO-related adRP, we devised a CRISPR-based, mutation-independent gene ablation and replacement (AR) compound therapy carried by a dual AAV2/8 system.

View Article and Find Full Text PDF

Retinal disorders such as retinitis pigmentosa, age-related retinal degeneration, oxygen-induced retinopathy, and ischemia-reperfusion injury cause debilitating and irreversible vision loss. While the exact mechanisms underlying these conditions remain unclear, there has been a growing body of evidence demonstrating the pathological contributions of oxidative stress across different cell types within the eye. Nuclear factor erythroid-2-related factor (Nrf2), a transcriptional activator of antioxidative genes, and its regulator Kelch-like ECH-associated protein 1 (Keap1) have emerged as promising therapeutic targets.

View Article and Find Full Text PDF
Article Synopsis
  • A nationwide study from Taiwan investigated the link between sleep apnea (SA) and cataract risk, finding a significant association between the two.
  • The study analyzed data from over 6,000 SA patients and 32,000 control participants, revealing that patients with SA had a higher incidence of cataracts after adjusting for various factors.
  • It concluded that sleep apnea is an independent risk factor for cataracts and emphasized the importance for healthcare providers to monitor this potential complication in SA patients.
View Article and Find Full Text PDF
Article Synopsis
  • The early 21st century has seen significant advancements in pharmacochemical and gene-based therapies, particularly for rare genetic diseases.
  • Initial successes with novel genome editing technologies have been applied to inherited retinal dystrophies, showcasing promising treatment outcomes.
  • Current and future clinical trials are focusing on conditions like choroideremia and age-related macular degeneration, with innovative strategies like base and prime editing heralding a new era of precision medicine.
View Article and Find Full Text PDF

Atypical Usher syndrome (USH) is poorly defined with a broad clinical spectrum. Here, we characterize the clinical phenotype of disease caused by variants in , and .Chart review evaluating demographic, clinical, imaging, and genetic findings of 19 patients from 18 families with a clinical diagnosis of retinal disease and confirmed disease-causing variants in , or .

View Article and Find Full Text PDF
Article Synopsis
  • Cone dystrophy with supernormal rod response (CDSRR) is a rare inherited retinal disease that can be misdiagnosed, especially in patients taking hydroxychloroquine (HCQ) for conditions like lupus.
  • A case study of a 38-year-old male revealed unique retinal patterns through various examinations, leading to a diagnosis of CDSRR due to a specific mutation in a gene related to potassium channels.
  • This case highlights the importance of thorough diagnostic methods, such as multimodal imaging and electroretinography, in distinguishing inherited retinal disorders from acquired conditions.
View Article and Find Full Text PDF

Macular degeneration (MD) is characterized by the progressive deterioration of the macula and represents one of the most prevalent causes of blindness worldwide. Abnormal intracellular accumulation of lipid droplets and pericellular deposits of lipid-rich material in the retinal pigment epithelium (RPE) called drusen are clinical hallmarks of different forms of MD including Doyne honeycomb retinal dystrophy (DHRD) and age-related MD (AMD). However, the appropriate molecular therapeutic target underlying these disorder phenotypes remains elusive.

View Article and Find Full Text PDF

Background: To analyze multiple imaging modalities in patients with Bietti crystalline dystrophy (BCD) and to investigate which factors from these modalities are associated with best corrected visual acuity (BCVA).

Methods: In this retrospective study, 40 eyes from 22 patients with BCD were included and were separated into group 1 (BCVA ≤20/200) and group 2 (BCVA > 20/200). Data including BCVA and characteristic findings from near-infrared reflectance (NIR) imaging, fundus autofluorescence (FAF), and spectral domain-optic coherence tomography (SD-OCT) were analyzed and compared.

View Article and Find Full Text PDF

Purpose: The purpose of this paper was to discuss manifestations of primary mitochondrial dysfunctions and whether the retinal pigment epithelium or the photoreceptors are preferentially affected.

Methods: A retrospective analysis was performed of patients with clinically and laboratory confirmed diagnoses of maternally inherited diabetes and deafness (MIDD) or Kearns-Sayre syndrome (KSS). Patients underwent full ophthalmic examination, full-field electroretinogram, and multimodal imaging studies, including short-wavelength autofluorescence, spectral domain-optical coherence tomography, and color fundus photography.

View Article and Find Full Text PDF

Retinitis pigmentosa (RP), the most common form of rod-cone dystrophy, is caused by greater than 3100 mutations in more than 71 genes, many of which are preferentially expressed in rod photoreceptors. Cone death generally follows rod loss regardless of the underlying pathogenic mutation. Preventing the secondary loss of cone photoreceptors would preserve central visual acuity and substantially improve patients' quality of life.

View Article and Find Full Text PDF

Background: Optical coherence tomography (OCT) is a non-invasive imaging test that provides easily obtainable and highly reproducible cross-sectional images of the retina. Improved modalities of the OCT that are capable of providing high quality images of not only the retina, but also the deeper structures and vasculature have been developed, including swept-source OCTs and OCT angiography.

Materials And Methods: Review.

View Article and Find Full Text PDF

Fundus autofluorescence is a valuable imaging tool in the diagnosis of inherited retinal dystrophies. With the advent of gene therapy and the numerous ongoing clinical trials for inherited retinal degenerations, quantifiable and reliable outcome measurements continually need to be identified. In this retrospective analysis, normalized and non-normalized short-wavelength (SW-AF) and near-infrared (NIR-AF) autofluorescence images of ten patients with mutations in visual cycle (VC) genes and nineteen patients with mutations in phototransduction (PT) genes were analyzed.

View Article and Find Full Text PDF

Purpose: To characterize the progression of optical gaps and expand the known etiologies of this phenotype.

Design: Retrospective cohort study.

Methods: Thirty-six patients were selected based on the identification of an optical gap on spectral-domain optical coherence tomography (OCT) from a large cohort of patients (N = 746) with confirmed diagnoses of inherited retinal dystrophy.

View Article and Find Full Text PDF

Purpose: To determine whether there are differences in the prevalence of intraretinal pigment migration (IPM) across ages and genetic causes of inherited retinal dystrophies (IRDs).

Design: Retrospective cohort study.

Methods: Patients were evaluated at a single tertiary referral center.

View Article and Find Full Text PDF

Background: The C677T variant of the MTHFR (5,10-Methylenetetrahydrofolate reductase) gene is associated with increased susceptibility to homocystinuria (OMIM#236250), neural tube defects (OMIM#601634), schizophrenia (OMIM#181500), thromboembolism (OMIM#188050), and vascular diseases. Protein S deficiency is also associated with an increased risk of thromboembolism from reduced thrombin generation. In this report, we describe the case of a patient who presented with multiple retinal vein occlusions likely caused by an underlying combination of a homozygous MTHFR C677T variant and protein S deficiency.

View Article and Find Full Text PDF
Article Synopsis
  • Retinitis pigmentosa (RP) is a serious eye condition affecting over 1.5 million people worldwide, leading to permanent vision loss due to its complex genetic nature.
  • This study explores how targeting pyruvate kinase M2 (PKM2) through metabolic reprogramming can potentially treat RP by promoting photoreceptor survival in a Pde6β preclinical model.
  • Results showed that inhibiting PKM2 led to thicker retinal layers and improved photoreceptor function, suggesting that altering metabolic pathways may offer new therapeutic options for RP.
View Article and Find Full Text PDF

: To evaluate the long-term progression of autosomal recessive retinitis pigmentosa (RP) due to mutations in using multimodal imaging and a quantitative analytical approach.: Whole exome sequencing (WES) and targeted capture sequencing were used to identify mutation. Fundus photography, short-wavelength autofluorescence (SW-AF), spectral-domain optical coherence tomography (SD-OCT) imaging, and electroretinography (ERG) were analyzed.

View Article and Find Full Text PDF

Background: Mutations in the Kelch-like protein 7 (KLHL7) represent a recently described and, to date, poorly characterized etiology of inherited retinal dystrophy. Dominant mutations in KLHL7 are a cause of isolated, non-syndromic retinitis pigmentosa (RP). In contrast, recessive loss-of-function mutations are known to cause Crisponi or Bohring-Opitz like cold induced sweating syndrome-3 (BOS-3).

View Article and Find Full Text PDF

A key challenge for the diagnosis and treatment of complex human diseases is identifying their molecular basis. Here, we developed a unified computational framework, URSA (Unveiling RNA Sample Annotation for Human Diseases), that leverages machine learning and the hierarchy of anatomical relationships present among diseases to integrate thousands of clinical gene expression profiles and identify molecular characteristics specific to each of the hundreds of complex diseases. URSA can distinguish between closely related diseases more accurately than literature-validated genes or traditional differential-expression-based computational approaches and is applicable to any disease, including rare and understudied ones.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessions396kqi1i0h53c65ad9ee7tlduhj6as3): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once