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Comparison of the laser-induced choroidal neovascularization model pathology in C57BL/6J mice from different vendors.

1:00 PM – 3:00 PM MDT on Tuesday, May 3 | F0403

Authors: Vähätupa M, Kalesnykas G, Jokinen V, Nevalainen T, Tähtivaara L, Thapa R, Koskenniemi H, Tenhunen A, Lappeteläinen B, Haapaniemi AM, Kvietkauskiene N, Jarutis J, Bijeikis S, Kaja S, Cerrada-Gimenez M

Purpose: The mouse laser-induced choroidal neovascularization (CNV) model is the most popular experimental model to mimic the wet form of age-related macular degeneration (AMD). In this study we aimed to compare the differences in CNV pathology between C57BL/6J mice from different vendors.

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Efficacy of Tandospirone and cytokine production in the mouse Blue Light Damage model of Dry AMD.

3:00 PM – 5:00 PM MDT on Wednesday, May 4 | F0389

Authors: Jamison JA, Ghosh AK, Ogle S, Pappenhagen N, Bacellar-Galdino M, Kaja S

Purpose: Blue light induced photooxidative stress (BLD) is an established model of advanced geographic atrophy observed in patients with dry AMD. 5-HT1A agonists have demonstrated neuroprotection in rat BLD studies and other mouse CNS injury models. The purpose of this work was to evaluate the 5-HT1A agonist tandospirone (tando) to provide protection in the mouse BLD model, and to measure cytokine production in the Balb/C mouse retina at 1-7 days after light exposure.

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Pooled human immune globulins protect against neutrophil activation.

Authors: Rao VR, Mun C, Jain S, Kaja S

Purpose: Our previous studies have demonstrated the presence of anti-citrullinated protein autoantibodies (ACPA) in ocular surface washes from patients with autoimmune dry eye disease (DED). Moreover, autoimmune DED was responsive to treatment with pooled human immune globulin (pooled IgG) eye drops. The purpose of this study was to develop a plate reader-based in vitro assay to evaluate therapeutics targeting neutrophil activation and neutrophil extracellular traps formation (NETosis). Specifically, the efficacy of pooled IgG in preventing neutrophil activation and NETosis were assessed.

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PLL-g-PEG inhibits antibody-drug conjugate uptake into human corneal epithelial cells in vitro.

Authors: Kleinman D, Hakkarainen JJ, Ghosh AK, Ogle S, Sill K, Mendelsohn B, Mitchnick M, Kaja S

Purpose: Corneal toxicity secondary to antibody-drug conjugates (ADCs) is a common and clinically significant adverse event that interferes with ADC dosing and could ultimately affect a patient’s response to ADC therapy. Effective interventions that either prevent or mitigate this drug-induced keratopathy are lacking. Evidence suggests that ADCs can enter corneal epithelial cells or their precursors indirectly through macropinocytosis, often with no involvement of the targeted receptor. Once internalized, the drug is cleaved from the ADC releasing a cytotoxic small molecule. This present study was based on the rationale that preventing the uptake of an ADC into off-target tissue should mitigate toxicity and the knowledge that charge plays an important role in the interaction of immunoconjugates with cell membranes. The hypothesis that locally delivered poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG) can inhibit ADC uptake into human corneal epithelial cells was tested.

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Visual behaviour-based screening of a randomised chemical library identifies small molecules that restore vision.

Authors: Kennedy B, Fehilly J, Cerrada-Gimenez M, Kaja S, Kalesnykas G, Scoffin R, O’Brien J

Purpose: Retinal and macular degenerations are conditions with progressive photoreceptor or retinal pigment epithelium (RPE) dysfunction resulting in blindness. Most patients lack effective treatments to preserve vision. Efficient and effective phenotypic screening of randomised compound libraries can uncover first-in-class drugs. Here, using a bespoke drug discovery workflow we identify drugs rescuing vision.

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Improving the penetration of Dexamethasone to the posterior segment of eye using topically applied penetration enhancing agents.

Authors: Thareja A, Leigh T, Hakkarainen JJ, Alvarez-Lorenzo C, Hughes H, Fernandez-Trillo F, Blanch RJ, Ahmed Z

Purpose: Disease and damage in the posterior segment of the eye are a major global cause of blindness. Topical eye-drop treatments are less effective because therapeutic molecules penetrate ocular tissue barriers poorly. We investigated penetration enhancement of the most commonly used anti-inflammatory drug, dexamethasone sodium phosphate (DSP), after topical delivery with three penetration enhancing agents (PEAs) — an in-house synthesized novel helical polymer and two commonly used cell penetrating peptides (CPPs), TAT and Penetratin.