4.2 Article

Effect of Choroidal Perfusion on Ocular Tissue Distribution After Intravitreal or Suprachoroidal Injection in an Arterially Perfused Ex Vivo Pig Eye Model

Journal

JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
Volume 29, Issue 8, Pages 715-722

Publisher

MARY ANN LIEBERT, INC
DOI: 10.1089/jop.2013.0063

Keywords

-

Ask authors/readers for more resources

Purpose: To compare tissue distribution of dye-drug surrogates after intravitreal (IVT) and suprachoroidal (SCS) delivery to determine the influence of drug lipophilicity and choroidal circulation. Methods: Thirty-two pig eyes were collected immediately after euthanasia. Sixteen eyes were perfused for 30min through one long posterior ciliary artery with nondye containing nutrient media. An IVT or SCS injection was performed with either a 100L balanced salt solution (BSS, n=8), 1% sodium fluorescein (NaF, n=12) or 0.12% lipophilic carbocyanine dye (DiI, n=12). Globes were maintained at 37 degrees C for 15min, and then snap-frozen and dissected. Aqueous extraction and measurement of NaF or DiI concentration was performed using spectrophotometry and spectrofluorometry, respectively. Results: After SCS delivery of NaF scleral, iris-ciliary body, choroidal and vitreous dye levels were higher in nonperfused eyes compared to perfused eyes. After DiI SCS or IVT delivery, no significant differences were found in dye tissue concentrations in perfused eyes compared to nonperfused eyes. Following perfusion, a better and even drug distribution was found in the retinal pigmented epithelium (RPE)-choroid following IVT and SCS delivery of the hydrophilic drug and after IVT injection of the lipophilic drug compared to nonperfused eyes. Conclusions: Choroidal circulation reduces the tissue drug concentration of the hydrophilic drug suggesting an early clearance mechanism after SCS delivery. SCS injections of lipid and hydrophilic drugs allowed direct drug delivery to the retina and RPE-choroid with limited exposition to the anterior segment.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.2
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Veterinary Sciences

Role of Leptospira spp. testing and ocular examination in horses with equine recurrent uveitis: A retrospective study of 63 horses

N. E. Himebaugh, B. C. Gilger

Summary: This retrospective case series study found that positive leptospiral testing results were associated with younger horses and ocular posterior segment clinical disease, leading to poor prognosis for vision in horses with aqueous humour titres to any leptospiral serotype, especially L. bratislava serovar.

EQUINE VETERINARY EDUCATION (2022)

Review Biochemistry & Molecular Biology

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

Brian C. Gilger, Matthew L. Hirsch

Summary: This paper reviews the role of human leukocyte antigen G (HLA-G) in the eye, explores the potential therapeutic applications of AAV gene transfer and expression of HLA-G in different ocular tissues, and discusses the efficacy of these treatments in animal models of various eye diseases. The findings suggest that AAV-HLA-G could be an effective treatment for immune-mediated, inflammatory, and neovascular diseases of the eye.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Veterinary Sciences

Polidocanol monotherapy for a superficial orbital venous malformation in a horse

Tara M. Stonex, Ashley E. Zibura, Michael Andres, Brian C. Gilger, Annie Oh

Summary: This study describes the use of 1% polidocanol as the sole treatment for a superficial orbital venous malformation in a horse. The results show that polidocanol treatment was well tolerated and led to clinical improvement in the horse.

VETERINARY OPHTHALMOLOGY (2022)

Article Agriculture, Dairy & Animal Science

Corynebacterium conjunctivae: A New Corynebacterium Species Isolated from the Ocular Surface of Healthy Horses

Jose F. Fernandez-Garayzabal, Stacey LaFrentz, Almudena Casamayor, Eva Abarca, Haitham H. Mohammed, Rosemary S. Cuming, Cova R. Arias, Lucas Dominguez, Ana Vela

Summary: This study identified and characterized a new commensal species, Corynebacterium conjunctivae, recovered from the conjunctival sac of healthy adult horses. The bacterial isolates displayed specific cellular morphology, biochemical properties, and gene sequences. This research provides important insights into the diversity of commensal bacteria in horse eyes.

ANIMALS (2022)

Article Veterinary Sciences

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

Brian C. Gilger

Summary: This article discusses the importance of studying immune-mediated ocular diseases in the development of innovative therapies, such as cell and gene therapy. Recent studies on cell and gene therapy are reviewed to highlight the significance of One Health initiatives in treating ocular diseases. The results suggest that autologous subconjunctival BM-MSC therapy may be a promising alternative treatment for immune-mediated ocular diseases.

AMERICAN JOURNAL OF VETERINARY RESEARCH (2022)

Article Veterinary Sciences

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

Brian C. Gilger

Summary: This article reviews naturally occurring ocular diseases in animals and emphasizes how understanding these diseases contributes to one health initiatives, particularly in the context of common ocular diseases shared by animals and humans.

JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION (2022)

Article Multidisciplinary Sciences

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

Elizabeth Crabtree, Katy Uribe, Sara M. Smith, Darby Roberts, Jacklyn H. Salmon, Jacquelyn J. Bower, Liujiang Song, Prabhakar Bastola, Matthew L. Hirsch, Brian C. Gilger

Summary: This study investigated the therapeutic efficacy of AAV8-Equine-IL10 gene therapy for the treatment of experimental autoimmune uveitis (EAU) in rats. The results showed that AAV8-Equine-IL10 treatment effectively reduced inflammation and cell counts, indicating its potential as a safe and effective treatment for uveitis.

PLOS ONE (2022)

Editorial Material Veterinary Sciences

Solving an eye condition by looking to the rear

Brian C. Gilger

EQUINE VETERINARY EDUCATION (2023)

Article Ophthalmology

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

Nicole E. Himebaugh, James B. Robertson, Keith Weninger, Brian C. Gilger, Bjorn Ekesten, Annie Oh

Summary: The study aimed to assess the transmission of UV radiation through intact enucleated globes of different species using spectrophotometry. The results showed that cats and dogs allowed the most transmission of UV radiation, while pigs and humans allowed the least. A small amount of transmission was detected in the globes of rabbits and horses. These findings will support further vision research for training companion, working, and service animals.

EXPERIMENTAL EYE RESEARCH (2023)

Article Veterinary Sciences

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

Hannah L. Smith, Alix K. Berglund, James B. Robertson, Lauren V. Schnabel, Richard J. McMullen, Brian C. Gilger, Annie Oh

Summary: The study aimed to investigate the effect of gentamicin on CD3+ T-lymphocyte proliferation and cell viability using an in vitro cell culture model. Three adult horses were used for the experiment. Peripheral blood lymphocytes were treated with different concentrations of gentamicin and stimulated to proliferate. Live cell counts and fluorescent intensity data were collected. Statistical analysis showed no significant differences between gentamicin concentrations or formulations in terms of cell viability and proliferation. The results suggest that low-dose intravitreal gentamicin may not suppress the immune response.

VETERINARY OPHTHALMOLOGY (2023)

Article Medicine, Research & Experimental

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

Jacob P. Nilles, Darby Roberts, Jacklyn H. Salmon, Liujiang Song, Carly O'Dea, Lindsay T. Marjoram, Jacquelyn J. Bower, Matthew L. Hirsch, Brian C. Gilger

Summary: This study evaluated the efficacy of adeno-associated virus (AAV) gene therapy encoding human leukocyte antigen G (HLA-G) to inhibit ocular graft versus host disease (OGvHD). The results showed that eyes treated with AAV had significantly reduced clinical signs of OGvHD and lower limbal mononuclear cell count. These findings support the potential of HLA-G-based gene therapy as an effective treatment for OGvHD.

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT (2023)

Article Veterinary Sciences

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

Elizabeth Esdaile, Kelly E. Knickelbein, Callum G. Donnelly, Michelle Ferneding, Monica J. Motta, Brett D. Story, Felipe Avila, Carrie J. Finno, Brian C. Gilger, Lynne Sandmeyer, Sara Thomasy, Rebecca R. Bellone

Summary: This study identifies the presence of congenital stationary night blindness (CSNB) in multiple horse breeds and identifies the genetic variations associated with this disease. The study also provides recommendations for treatment, emphasizing the importance of genetic testing in horses with the identified genetic variations.

VETERINARY OPHTHALMOLOGY (2023)

Article Microbiology

Phase-Dependent Differential In Vitro and Ex Vivo Susceptibility of Aspergillus flavus and Fusarium keratoplasticum to Azole Antifungals

Darby Roberts, Jacklyn Salmon, Marc A. Cubeta, Brian C. Gilger

Summary: This study aims to explore the differences in fungal response to topical antifungal treatment at different stages of fungal keratitis (FK) development. The results show that fungal development stage is correlated with efficacy, and traditional antifungal susceptibility testing methods are not applicable to more advanced developmental stages. A revised method of antifungal susceptibility testing may better predict fungal response in the clinical setting.

JOURNAL OF FUNGI (2023)

Article Veterinary Sciences

Use of Biologics and Stem Cells in Equine Ophthalmology

Brian Christopher Gilger

VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE (2023)

Article Cell & Tissue Engineering

Induced Pluripotent Stem Cell-Derived Corneal Cells: Current Status and Application

Nasif Mahmood, Taylor Cook Suh, Kiran M. Ali, Eelya Sefat, Ummay Mowshome Jahan, Yihan Huang, Brian C. Gilger, Jessica M. Gluck

Summary: Deficiency and dysfunction of corneal cells can lead to blindness in corneal diseases. However, there is a lack of adequate cell sources for regenerative cell therapies and engineered corneal tissue. The discovery of induced pluripotent stem cells (iPSCs) provides an opportunity to generate corneal cells autologously and in unlimited quantities. iPSCs have advantages over other stem cell sources in terms of differentiation potential and ethical concerns. They have been used to model corneal disorders and diseases, perform drug testing, and explore regenerative medicine. Building stem cell banks with HLA-homozygous cell lines can provide cost- and time-efficient allogeneic alternatives to expensive autologous treatments.

STEM CELL REVIEWS AND REPORTS (2022)

No Data Available