Ophthalmology Commons^™

Drug Delivery To Posterior Intraocular Tissues: Third Annual Arvo/Pfizer Ophthalmics Research Institute Conference, Henry F. Edelhauser, Jeffrey H. Boatright, John M. Nickerson, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

The third Annual ARVO/Pfizer Ophthalmic Research Institute Conference was held Friday and Saturday, May 4 and 5, 2007 at the Fort Lauderdale Grande Hotel and Yacht Club, Fort Lauderdale, Florida. The conference, funded by the ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to develop strategies to address drug delivery to posterior intraocular tissues—a topic of great interest, as the major route of drug delivery is via intravitreous injection.

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …

Epigenetic Modification Prevents Excessive Wound Healing And Scar Formation After Glaucoma Filtration Surgery, Ajay Sharma, Govindaraj Anumanthan, Marcos Reyes, Huiyi Chen, Jason W. Brubaker, Saad Siddiqui, Suneel Gupta, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. The purpose of this study was to determine the efficacy of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi), in prevention of excessive wound healing and scar formation in a rabbit model of glaucoma filtration surgery (GFS).

METHODS. A rabbit model of GFS was used. Rabbits that underwent GFS received balanced salt solution, or SAHA (50 lM), or mitomycin C (0.02%). Clinical scores of IOP, bleb vascularity, and slit-lamp examination were performed. On postoperative day 14, rabbits were killed and the bleb tissues were collected for evaluation of tissue fibrosis with hematoxylin and eosin, Masson trichrome, a-smooth muscle …

Development Of A Novel In Vivo Corneal Fibrosis Model In The Dog, K. M. Gronkiewicz, Elizabeth A. Giuliano, K. Kuroki, F. Bunyak, Ajay Sharma, L. B. C. Teixeira, C. W. Hamm, R. R. Mohan

Pharmacy Faculty Articles and Research

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading …

Characterization Of Inhibitor Of Differentiation (Id) Proteins In Human Cornea, Rajiv R. Mohan, Brandie R. Morgan, Govinduraj Anumanthan, Ajay Sharma, Shyam S. Chaurasia, Frank G. Rieger

Pharmacy Faculty Articles and Research

Inhibitor of differentiation (Id) proteins are DNA-binding transcription factors involved in cellular proliferation, migration, inflammation, angiogenesis and fibrosis. However, their expression and role in the cornea is unknown. The present study was undertaken to characterize the expression of Id proteins and their interactions with the pro-fibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and anti-fibrotic cytokine, bone morphogenic protein 7 (BMP7) in human cornea. Human donor corneas procured from Eye Bank were used. Id proteins were localized in human corneal sections using immunofluorescence. Primary cultures of human corneal fibroblasts (HCF) were established and treated with either TGFβ1 (5 ng/ml) or BMP7 …