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Study on erythropoietin subconjunctival administration in a glaucoma animal model
Publication . Resende, Ana Paula Simões Nunes de; Delgado, Esmeralda Sofia da Costa; São Braz, Berta Maria Fernandes Ferreira
Glaucoma is the number one cause of irreversible vision loss worldwide. Death of retinal ganglion cells (RGC), which results in the progressive loss of visual function, occurs in glaucoma and other ocular diseases caused by hypoxia and ischemia. Although glaucoma is a multifactorial neurodegenerative disease, the only currently method of treatment involves reduction of intraocular pressure and, at the present, there is no effective treatment to prevent RGC apoptosis. Notably, it has been reported that erythropoietin (EPO), a cytokine hormone produced in response to hypoxia, has significant neuroprotective and neuroregenerative properties in several types of ocular disorders. Pre-clinical studies in glaucoma animal models involving EPO have yielded very promising results. All studies involving EPO ocular administrations have used systemic, intravitreal or retrobulbar administration to reach retinal desired EPO concentrations. However, EPO chronic systemic administration can lead to adverse side effects related with haematopoiesis stimulation, while intravitreal or retrobulbar administrations are invasive procedures that can induce several complications such as endophthalmitis, retinal detachment, vitreitis, retinitis, choroiditis or cataracts.
This thesis aims to clarify if EPO’s neuroprotection could be achieved by a non-invasive and safe periocular administration route without adverse effects. Being so, this work evaluates the subconjunctival route as an alternative for EPO administration in glaucoma disease. After the first in vitro study, where the permeation of EPO across the periocular tissues was quantified, all work was developed in in vivo models. EPO’s ocular permeation after subconjunctival administration was tested, both in physiological and glaucomatous conditions. Furthermore, both retinal morphological and physiological effects of EPO administered by this route were assessed in glaucomatous animals.
Results showed that EPO, when administered subconjunctivally, can permeate the main ocular barriers and reach RGC layers, in both physiological and glaucomatous conditions, without significant local or systemic side effects. More than showing that EPO can reach the retina by this route, results also concluded that subconjunctival EPO administration seems to have structural and functional beneficial effects on the retina after glaucoma induction in rats.
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Fundação para a Ciência e a Tecnologia
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SFRH
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SFRH/BD/65793/2009