gene therapy eye

PURPOSE: Uveitis is a heterogenous group of inflammatory eye disease for which current cytokine-targeted immune therapies are effective for only a subset of patients. We hypothesized that despite pathophysiologic nuances that differentiate individual disease states, all forms of eye inflammation might share common mechanisms for immune cell recruitment. Identifying these mechanisms is critical for developing novel, broadly acting therapeutic strategies. DESIGN: Experimental study...

PURPOSE: To investigate the effect of rose bengal photodynamic therapy on lipopolysaccharide-induced inflammation in human corneal fibroblasts. Furthermore, to analyze potential involvement of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways in this process. METHODS: Human corneal fibroblast cultures underwent 0-2.0 µg/mL lipopolysaccharide treatment, and 24 h later rose bengal photodynamic therapy (0.001% RB, 565 nm wavelength illumination, 0...

Fibrotic diseases are characterised by myofibroblast differentiation, uncontrolled pathological extracellular matrix accumulation, tissue contraction, scar formation and, ultimately tissue / organ dysfunction. The cornea, the transparent tissue located on the anterior chamber of the eye, is extremely susceptible to fibrotic diseases, which cause loss of corneal transparency and are often associated with blindness. Although topical corticosteroids and antimetabolites are extensively used in the management of corneal fibrosis, they are associated with glaucoma, cataract formation, corneoscleral melting and infection, imposing the need of far more effective therapies...

Virus-like particles (VLP) are a promising tool for intracellular gene delivery, yet their potential in ocular gene therapy remains underexplored. In this study, we bridged this knowledge gap by demonstrating the successful generation and application of vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped mouse PEG10 (MmPEG10)-VLP for intraocular mRNA delivery. Our findings revealed that PEG10-VLP can efficiently deliver GFP mRNA to adult retinal pigment epithelial cell line-19 (ARPE-19) cells, leading to transient expression...

Excessive exposure to blue light can cause retinal damage. Hydrogen-rich saline (HRS), one of the hydrogen therapies, has been demonstrated to be effective in eye photodamage, but the effect on the expression of melanopsin in intrinsically photosensitive retinal ganglion cells (ipRGCs) is unknown. In this study, we used a rat model of light-induced retinal injury to observe the expression of melanopsin after HRS treatment and to determine the effect of HRS on retinal ganglion cell protection. Adult SD rats were exposed to blue light (48 h) and treated with HRS for 0, 3, 7, and 14 days...

Biallelic mutations in the RPE65 gene affect nearly 8% of Leber Congenital Amaurosis and 2% of Retinitis Pigmentosa cases. Voretigene neparvovec (VN) is the first gene therapy approach approved for their treatment. To date, real life experience has demonstrated functional improvements following VN treatment, which are consistent with the clinical trials outcomes. However, there is currently no consensus on the characteristics for eligibility for VN treatment. We reviewed relevant literature to explore whether recommendations on patient eligibility can be extrapolated following VN marketing...

Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions...

While the involvement of thermosensitive transient receptor potential channels (TRPs) in dry eye disease (DED) has been known for years, their expression in the meibomian gland (MG) has never been investigated. This study aims to show their expression and involvement in the lipogenesis of the MG, providing a possible new drug target in the treatment of DED. Our RT-PCR, Western blot and immunofluorescence analysis showed the expression of TRPV1 , TRPV3 , TRPV4 and TRPM8 in the MG at the gene and the protein level...

There is a huge unmet need for new treatment modalities for ocular surface inflammatory disorders (OSIDs) such as dry eye disease and meibomian gland dysfunction. Mesenchymal stem cell therapies may hold the answer due to their potent immunomodulatory properties, low immunogenicity, and ability to modulate both the innate and adaptive immune response. MSC-like cells that can be isolated from the corneal stroma (C-MSCs) offer a potential new treatment strategy; however, an optimized culture medium needs to be developed to produce the ideal phenotype for use in a cell therapy to treat OSIDs...

PURPOSE: Achromatopsia (ACHM) is an autosomal recessive retinal disease associated with reduced or absent cone function. There is debate regarding the extent to which cone structure shows progressive degeneration in patients with ACHM. Here, we used optical coherence tomography (OCT) images to evaluate outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) integrity over time in individuals with ACHM. METHODS: Sixty-three individuals with genetically confirmed ACHM with follow-up ranging from about 6 months to 10 years were imaged using either Bioptigen or Cirrus OCT...

Amidst rapid advancements in ocular gene therapy, understanding patient perspectives is crucial for shaping future treatment choices and research directions. This international cross-sectional survey evaluated knowledge, attitudes, and perceptions of ocular genetic therapies among potential recipients with inherited retinal diseases (IRDs). Survey instruments included the Attitudes to Gene Therapy-Eye (AGT-Eye), EQ-5D-5L, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and Patient Attitudes to Clinical Trials (PACT-22) instruments...

Lowe syndrome, a rare X-linked multisystem disorder presenting with major abnormalities in the eyes, kidneys, and central nervous system, is caused by mutations in OCRL gene (NG_008638.1). Encoding an inositol polyphosphate 5-phosphatase, OCRL catalyzes the hydrolysis of PI(4,5)P2 into PI4P. There are no effective targeted treatments for Lowe syndrome. Here, we demonstrate a novel gene therapy for Lowe syndrome in patient fibroblasts using an adenine base editor (ABE) that can efficiently correct pathogenic point mutations...

BACKGROUND: Frequent anti-vascular endothelial growth factor A (VEGF-A) injections reduce the risk of rapid and severe vision loss in patients with neovascular age-related macular degeneration (nAMD); however, due to undertreatment, many patients lose vision over time. New treatments that provide sustained suppression of VEGF-A are needed. RGX-314 (currently known as ABBV-RGX-314) is an adeno-associated virus serotype 8 vector that expresses an anti-VEGF-A antigen-binding fragment, which provides potential for continuous VEGF-A suppression after a single subretinal injection...

Corneal injury occurs frequently which may lead to serious visual impairment. Rapid and efficient re-epithelialization after corneal epithelial injury is the key issue for maintaining corneal homeostasis. Among various treatment strategies, microRNA (miR)-based therapy shows great potential. However, structural limitations of miRNAs hinder its biomedical functionality. Nucleic acid nanotechnology is an appealing candidate for gene delivery because of its flexible modification and excellent biocompatibility...

Childhood eye cancers, although rare, present substantial health challenges, affecting the pediatric population with a remarkable impact on their lives and families. This comprehensive review provides insights into the various types of ocular tumors, primarily focusing on malignant eye tumors, their genetic predispositions, and advancements in managing these conditions. Understanding the genetic risk factors is crucial for early detection, risk assessment, and the development of targeted therapies. This review discusses genome-wide association (GWAS) and next-generation sequencing (NGS) studies to find common and rare genetic variants...

The cornea is a transparent and vitally multifaceted component of the eye, playing a pivotal role in vision and ocular health. It has primary refractive and protective functions. Typical corneal dysfunctions include opacities and deformities that result from injuries, infections, or other medical conditions. These can significantly impair vision. The conventional challenges in managing corneal ailments include the limited regenerative capacity (except corneal epithelium), immune response after donor tissue transplantation, a risk of long-term graft rejection, and the global shortage of transplantable donor materials...

Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in complement factor H ( CFH ) and age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase-1 ( ARMS2/HTRA1 ). Genetic factors account for up to 70% of disease variability. However, population-based genetic risk scores are generally more helpful for clinical trial design and stratification of risk groups than for individual patient counseling...

Retinoblastoma is the most common primary malignant intraocular tumor in children. Seeding, specifically the dispersion of the tumor into the adjacent compartments, represents a major parameter determining the degree of retinoblastoma according to the International Classification of Retinoblastoma. In this article we focused on vitreous seeding, one of the main limiting factors in the successful "eye preservation treatment" of retinoblastoma. This article presents an overview of the history of vitreous seeding of retinoblastoma, established treatment procedures and new-research modalities...

Genetic diseases affecting the retina can result in partial or complete loss of visual function. Leber's Congenital Amaurosis (LCA) is a rare blinding disease, usually inherited in an autosomally recessive manner, with no cure. Retinal gene therapy has been shown to improve vision in LCA patients caused by mutations in the RPE65 gene (LCA2). However, little is known about how activity in central visual pathways is affected by the disease or by subsequent gene therapy. Functional MRI was used to assess retinal signal transmission in cortical and subcortical visual structures before and one year after retinal intervention...

PURPOSE: Choroidal neovascularization (CNV) accounts for the majority of severe vision loss in neovascular age-related macular degeneration (AMD). Despite therapies that target VEGF, patients are often under-responsive, require frequent eye injections to control disease, and eventually lose some vision despite chronic therapy implicating a multifactorial etiology in treatment response. Genetic studies implicate systemic immunity in AMD and systemic immune cells accumulate within CNV lesions, yet a role for these cells in anti-VEGF response remains undetermined...