Table of Contents - WOC 2012

FP-PHA-FR 99 (2)
A New Therapeutic Target for Neovascular Age-Related Macular
Degeneration
Ahmad Iqbal (1)
1. Ophthalmology and Visual Sciences, University of Nebraska Medical Center
Objective/Purpose: Wet age-related macular degeneration (AMD), which
accounts for most of AMD-related vision loss, is characterized by choroidal
neovascularization (CNV). The underlying mechanism involves pathological
recruitment of normal angiogenic signaling pathway such as the VEGF
pathway. Our objective was to characterize the role of another angiogenic
regulator, the Notch signaling, in CNV.
Methods: Choroid sclera complex, after laser-induced CNV in adult rats, were
examined for changes in CNV lesion volume and proangiogenic and
antiangiogenic gene expression after perturbation in Notch signaling.
Results: Activation of the canonical Notch pathway reduced the volume of CNV
lesions, and in contrast, activation of the pathway exacerbated CNV lesions.
Expression analysis identified genes associated with proangiogenesis (e.g.,
Ccr3) and antiangiogenesis (e,g., Vegfr1) as targets of Notch signalingmediated
choroid vascular homoeostasis, the disruption of which might
underlie CNV.
Conclusion: Notch signaling is a key regulator of CNV and thus a molecular
target for therapeutic intervention in wet AMD.
FP-PHA-FR 99 (3)
Topical Cysteamine Depleting Therapy in Patients with Occular
Cystinosis
AlHemidan Amal (1) , Tabbara Khalid (1)
1. King Faisal Specialists Hospital
Background: Ocular cystinosis is a common complication of the lysosomal
storage disease, cystinosis. Corneal cystine crystals may lead to corneal
erosions, epithelial defvects, photophobia and keratopathy. The corneal
crystals are accessible for evaluation and direct examination.
Purpose: To study the effects of topical cysteamine depleting therapy on
cystine crystals in the eye.
Methods: We included a total of 29 patients with nephropathic cystinosis. All
patients had ocular cystinosis. Patients had complete ophthalmologic
examination before and four weeks after treatment with topical cyctemine
0.55% eye drops. Symptoms of photophobia was graded as (0-4) The level of
cystine was recorded in all layers of the cornea. The presence of conjunctival
cystine crystals was also noted as present or absent. In addition, deposits of
cystine crystals in the iris and fundus were noted and the presence of crystals
was recorded. Electroretinogram (ERG) was performed on 8 patients.
Conclusions: Cysteamine 0.55% eye drops applied six times daily dissolved
corneal cystine crystals in the epithelium and superficial stromal layers. Cystine
crystals that were in the deep stromal layers showed no dissolution.
FP-PHA-FR 99 (4)
Development and Characterization of Thalidomide Implants for
Intraocular Application
Fialho Silvia (1) , Pereira Bruno (1) , Silva Luciana (1) , Silva-Cunha Armando (2)
1. Pharmaceutical and Biotechnological Development - Fundação Ezequiel
Dias
2. Faculty of Pharmacy, Federal University of Minas Gerais
Thalidomide can inhibit angiogenesis induced by bFGF and VEGF. Because of
that, interest has been growing in its use as antitumor agent and eye diseases
causing neovascularization. Intraocular implants composed of biodegradable
polymers are promising systems for drug delivery mainly because they can
release the drug for a long period and they do not require surgical removal.
Biodegradable implants containing thalidomide as the drug and PLGA 50:50
as the polymer were prepared by the hot molding technique using different
organic solvents. After, they were characterized using differential scanning
calorimetry, thermogravimetry and stereomicroscopy. The in vitro degradation
of the implants was evaluated using pH 7.0 buffer medium at 37°C under 30
rpm stirring. The thalidomide implant developed presented 1 mm diameter and
4 mm in length, which allows its intraocular application without the need of
surgery. The characterization results showed that the interaction between drug
and polymers, as well as the rate of degradation of the implant are different
when the solvent used in the preparation was modified, but no significant
changes in both polymer and drug were found that could alter thalidomide
delivery to the eye. Further studies are underway to evaluate anti-VEGF
properties and antiinflammatory activity of the implants developed.
WOC2012 Abstract Book
FP-PHA-FR 99 (5)
Memantine for Axonal Loss of Optic Neuritis: A Double Masked
Placebo Controlled Clinical Trial
Riazi Esfahani Mohammad (1) , Alami Zahra (1) , Niikdel Mojgan (1) , Aghsaeefard
Masood (1) , Faghihi Houshang (1)
1. Tehran University of Medical Sciences
Purpose: To determine the effect of memantine on axonal loss and visual
function during the course of optic neuritis (ON).
Methods: Seventy ON patients were randomly assigned to memantine or
placebo groups. For all patients, the following characteristics were recorded
and compared at the initial presentation and three months afterwards: visual
acuity, retinal nerve fiber layer (RNFL) thickness, visual field parameters (mean
deviation and pattern standard deviation), visual evoked potential (VEP), and
contrast sensitivity.
Results: The memantine and placebo groups did not have differences in any of
the measured characteristics at initial presentation except for VEP amplitude.
After three months, the only statistically significant difference between the
two groups was in RNFL thickness. Memantine group subjects had higher
thickness in nasal (p=0.02), superior (0.001), inferior (0.004) quadrants and
average (p=0.01). However, temporal quadrant thickness was not different
between two groups (p=0.19).
Conclusion: Memantine was effective in reduction of RNFL thinning, although
this structural difference was not associated with improved visual function.
FP-PHA-FR 99 (6)
Axitinib Modulates Hypoxia-Induced Blood-Retina Barrier
Permeability and Expression of Growth Factors
Liegl Raffael (1) , Thiele Sarah (1) , Haritoglou Christos (1) , Kampik Anselm (1) ,
Kernt Marcus (1)
1. Department of Ophthalmology, Ludwig-Maximilians-University Munich
Objective: Hypoxia-induced breakdown of the inner/outer blood–retina barrier
and increased expression of growth factors are closely associated with the
development of diabetic macular edema. Hence we investigated the effects
of the multikinase inhibitor axitinib on hypoxia-induced increased tissue
permeability, vascular endothelial growth factor A (VEGF), and platelet-derived
growth factor (PDGF) expression of human retinal pigment epithelial (RPE)
cells and human umbilical vein endothelial cells (HUVECs). Effects of axitinib
on the expression of VEGF receptors 1/2 (VEGFR-1/2) and PDGF receptor
beta (PDGFR-?) were also explored.
Methods: Primary human RPE cells and HUVECs were treated with axitinib
(0.5 µg/mL). Viability and expression of VEGFR-1/2 and PDGFR-?, and their
mRNAs, were investigated by reverse transcription-polymerase chain reaction
(RT-PCR) and immunohistochemistry. Cells were exposed to hypoxia. Viability,
tissue permeability, expression, and secretion of VEGF and PDGF were
determined by RT-PCR and enzyme-linked immunosorbent assays.
Results: Treatment with axitinib reduced expression of VEGFR-1/2 and
PDGFR-?. Hypoxia decreased cell viability and increased tissue permeability,
expression, and secretion of VEGF and PDGF. Axitinib significantly reduced
hypoxia-induced overexpression and secretion of the growth factors and tissue
permeability.
Conclusion: Our in vitro results suggest axitinib may have promising properties
as a potential treatment for diabetic macular edema.
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