Ocular toxicity, distribution, and shedding of intravitreal AAV-eqIL-10 in horses.

Non-infectious uveitis (NIU) is a painful recurrent disease affecting 2%-5% of horses. Current treatments require frequent administration with associated adverse events. In a previous study, intravitreal (IVT) adeno-associated virus (AAV) harboring equine interleukin-10 (eqIL-10) cDNA inhibited experimental uveitis in rats.

Treatment of equine keratomycosis, part 1: selection of appropriate therapy based on clinical presentation and diagnostic testing improves clinical outcomes.

Objective: To determine clinical outcome, treatment costs, and hospitalization duration in horses treated for keratomycosis and identify ophthalmic examination and diagnostic results associated with these outcomes.

Methods: This was a retrospective study of 126 equine keratomycosis cases between 2004 and 2020 with fungal infection confirmed on cytology, culture, and/or histopathology and a minimum of 1-month follow-up. Details of the ophthalmic examination, diagnostic test results, and treatment and cost outcomes were recorded.

Treatment of equine keratomycosis, part 2: reporting common systemic and ocular complications to enhance decision-making for equine clinicians and owners.

Objective: The primary aims were to provide descriptive data on systemic and ocular complications associated with the treatment of equine keratomycosis. The secondary aims were to determine if complication rates differ between treatment types or are related to surgical and anesthetic factors.

Methods: The study was a retrospective evaluation of 126 cases between 2004 and 2020 with confirmed fungal infection and recorded incidence of complications during hospitalization and surgical intervention if pursued.

A chimeric anti-vascularization immunomodulator prevents high-risk corneal transplantation rejection via ex vivo gene therapy.

Corneal blindness affects more than 5 million individuals, with over 180,000 corneal transplantations (CTs) performed annually. In high-risk CTs, almost all grafts are rejected within 10 years. Here, we investigated adeno-associated virus (AAV) ex vivo gene therapy to establish immune tolerance in the corneal allograft to prevent high-risk CT rejection.

Causes, treatment, and outcome of hyphema, fibrin, and vitreal hemorrhage in horses: 219 cases (2012-2023).

Objective: To determine the causes, time to resolution, effect of therapeutics, and ocular sequelae of hyphema, fibrin, and/or vitreal hemorrhage in horses.

Animals: 225 horses (219 eyes) who were diagnosed with hyphema, fibrin, and/or vitreal hemorrhage.

Methods: Records were retrospectively reviewed for the horses.

Current therapy and advancements in the treatment of equine fungal keratitis.

Equine fungal keratitis represents a substantial portion of keratitis cases in horses, with fungal involvement identified in approximately half of all infectious keratitis cases. Despite its prevalence, more comprehensive retrospective analyses are needed to better understand this condition. Outcomes vary, with approximately two-thirds of cases achieving complete healing with retained vision, although enucleation is often necessary.

Cold atmospheric plasma inactivates and biofilms and conidia .

and are common causative pathogens of fungal keratitis (FK), a severe corneal disease associated with significant morbidity and vision loss. Escalating incidence of antifungal resistance to available antifungal drugs poses a major challenge to FK treatment. Cold atmospheric plasma (CAP) is a pioneering nonpharmacologic antimicrobial intervention that has demonstrated potential as a broad-spectrum antifungal treatment.

Ultrasound biomicroscopic imaging parameters associated with outcome in equine infectious ulcerative keratitis and stromal abscesses.

Objective: To determine the predictive value of corneal ultrasound biomicroscopy (UBM) findings for the outcome of equine corneal disease.

Animals: 46 horses with a clinical diagnosis of either infectious ulcerative keratitis or stromal abscess.

Methods: Corneal UBM (VevoMD; UHF70; VisualSonics) of horses with infectious corneal disease presenting to the North Carolina State University Equine Ophthalmology Service from 2019 to 2023 were evaluated.

Phase-Dependent Differential In Vitro and Ex Vivo Susceptibility of and to Azole Antifungals.

Fungal keratitis (FK) is an invasive infection of the cornea primarily associated with and species. FK is treated empirically with a limited selection of topical antifungals with varying levels of success. Though clinical infections are typically characterized by a dense network of mature mycelium, traditional models used to test antifungal susceptibility of FK isolates exclusively evaluate susceptibility in fungal cultures derived from asexual spores known as conidia.

Additional evidence supports GRM6 p.Thr178Met as a cause of congenital stationary night blindness in three horse breeds.

Congenital stationary night blindness (CSNB) is an ocular disorder characterized by nyctalopia. An autosomal recessive missense mutation in glutamate metabotropic receptor 6 (GRM6 c.533C>T, p.

Application of Noggin-Coated Electrospun Scaffold in Corneal Wound Healing.

Purpose: The objective of this study is to develop and characterize electrospun corneal bandage infused with Noggin protein and evaluate its therapeutic potential in the treatment of superficial nonhealing corneal ulceration.

Methods: Electrospun nanofibrous scaffolds were created with different blend ratios of polycaprolactone and gelatin and coated with different concentrations of Noggin protein. Morphologic, mechanical, degradation, and surface chemistry of the developed scaffold was assessed.

Use of Biologics and Stem Cells in Equine Ophthalmology.

Regenerative therapy and biologics have the promise to treat equine ocular surface diseases, including corneal ulceration or immune-mediated keratitis, or intraocular diseases such as uveitis. The use of blood-derived products such as serum or platelet-rich plasma, mesenchymal stem cells, or amniotic membrane grafts may be beneficial for the treatment of ulcerative and chronic keratitis in horses. Furthermore, the use of stem cells or gene therapy has promise for the treatment of Intraocular diseases such as equine recurrent uveitis by providing efficacious, practical, and long-term therapy for these blinding diseases.

Ex vivo analysis of ultraviolet radiation transmission through ocular media and retina in select species.

The aim of this study was to assess the transmission of the ultraviolet (UV) radiation (200-400 nm) through intact enucleated globes of different species (dogs, cats, pigs, rabbits, horses, and humans) using spectrophotometry. Globes of cats (n = 6), dogs (n = 18), pigs (n = 10), rabbits (n = 6), horses (n = 10), and humans (n = 4) were analyzed. A 5-10 mm circular area of sclera and choroid from the posterior aspect of the globe was removed under a surgical microscope, leaving the retina intact in all species except the horse.

Effect of gentamicin on CD3+ T-lymphocyte proliferation for treatment of equine recurrent uveitis: An in vitro study.

Objective: The objective of the study was to determine the effect of gentamicin on CD3+ T-lymphocyte proliferation and cell viability using an in vitro cell culture model as a means of investigating the mechanism of action of low-dose intravitreal gentamicin injection.

Animals Studied: Three adult horses with no evidence of ophthalmic or systemic disease.

Procedure: Peripheral blood lymphocytes were treated with gentamicin at concentrations 37.

AAV-mediated expression of HLA-G for the prevention of experimental ocular graft vs. host disease.

Ocular graft versus host disease (OGvHD) develops after allogeneic hematopoietic stem cell transplantation (HSCT) and manifests as ocular surface inflammatory disease. This study evaluated the efficacy of adeno-associated virus (AAV) gene therapy encoding human leukocyte antigen G (HLA-G) to inhibit OGvHD. A major histocompatibility mismatch chronic OGvHD murine model was evaluated.

Prevalence, differences, and potential correlation to age, sex, breed, coat color, iris color, and geographic location in naturally occurring refractive errors in the normal equine eye from Germany and North Carolina.

Purpose: To evaluate the normal refractive state in horses in NCSU and ECMR and determine the prevalence of naturally occurring refractive errors and their association with breed, age, coat color, iris color, sex, and geographic location.

Methods: Horses from NCSU (January 2009-November 2012) and ECMR (January 2013-September 2016) underwent ophthalmic examination and streak retinoscopy. Location, color, breed, sex, and iris color were recorded.

Developing advanced therapeutics through the study of naturally occurring immune-mediated ocular disease in domestic animals.

This review, which is part of the "Currents in One Health" series, describes the importance of the study of immune-mediated ocular disease in the development of innovative therapeutics, such as cell and gene therapy for the eye. Recent examples of cell and gene therapy studies from the author's laboratory are reviewed to emphasize the importance of One Health initiatives in developing innovative therapies for ocular diseases. Spontaneous immune-mediated corneal disease is common in horses, cats, dogs, and humans.

How study of naturally occurring ocular disease in animals improves ocular health globally.

In this article, which is part of the Currents in One Health series, the role of naturally occurring ocular disease in animals is reviewed with emphasis on how the understanding of these ocular diseases contributes to one health initiatives, particularly the pathogenesis and treatment of ocular diseases common to animals and humans. Animals spontaneously develop ocular diseases that closely mimic those in humans, especially dry eye disease, herpes virus infection (cats), fungal keratitis (horses), bacterial keratoconjunctivitis, uveitis, and glaucoma. Both uveitis and glaucoma are common in domestic animals and humans, and many similarities exist in pathogenesis, genetics, and response to therapy.

Inhibition of experimental autoimmune uveitis by intravitreal AAV-Equine-IL10 gene therapy.

Equine recurrent uveitis (ERU) is a spontaneous, painful, and vision threatening disease affecting up to 25% of equine populations worldwide. Current treatments of ERU are non-specific and have many side effects which limits them to short-term use. In order to develop an effective therapy for ERU, we investigated the use of adeno-associated virus (AAV) gene therapy, exploiting a natural immune tolerance mechanism induced by equine interleukin-10 (Equine-IL10).

Polidocanol monotherapy for a superficial orbital venous malformation in a horse.

Objective: To describe the use of 1% polidocanol as the sole treatment for a superficial orbital venous malformation in a horse.

Animal: A 23-year-old Welsh Cobb cross gelding with a distensible swelling affecting the left lower eyelid, and secondary palpebral margin abnormalities and superficial keratitis.

Procedure: Color flow Doppler ultrasonography revealed non-pulsatile blood flow within the tortuous vascular network most consistent with a superficial orbital venous malformation appearing to involve the lateral palpebral and transverse facial veins.

Therapeutic Applications of Adeno-Associated Virus (AAV) Gene Transfer of HLA-G in the Eye.

The purpose of this paper is to review human leukocyte antigen G (HLA-G) in the eye, its role in immune tolerance, and the potential therapeutic use of AAV gene transfer and expression of HLA-G in various ocular tissues. Several studies are reviewed that demonstrate efficacy in animal models of disease, including intracorneal delivery of AAV-HLA-G to treat corneal inflammation and prevent corneal graft rejection, subconjunctival injection of AAV-HLA-G for ocular graft vs. host disease and potentially dry eye disease, and intravitreal injection of AAV-HLA-G to inhibit uveitis.

Peptide Inhibitors of MARCKS Suppress Endotoxin Induced Uveitis in Rats.

To determine if inhibition of Myristoylated Alanine Rich C Kinase Substrate (MARCKS) protein, using novel MARCKS inhibitor peptides, will reduce the severity of endotoxin-induced uveitis (EIU) in rats. EIU was induced in Lewis rats using subcutaneous administration of lipopolysaccharide. In the first phase of the study, 3 different novel MARCKS inhibitor peptides that mimic the N-terminal region of MARCKS (BIO-11006, or lower molecular weight analogs BIO-91201 or BIO-91202; Biomarck Pharmaceuticals, Ltd.