Intravitreal injection of the synthetic peptide LyeTx I b, derived from a spider toxin, into the rabbit eye is safe and prevents neovascularization in a chorio-allantoic membrane model

Author(s)

da Silva, Flavia Rodrigues ^[1] ; Brandao de Paiva, Mayara Rodrigues ^[1] ; Nunes Dourado, Lays Fernanda ^[1] ; Silva, Rummenigge Oliveira ^[1] ; da Silva, Carolina Nunes ^[1] ; da Costa, Bruna Lopes ^[1] ; Toledo, Cibele Rodrigues ^[1] ; de Lima, Maria Elena ^[2] ; da Silva-Cunha, Armando ^[1]

Affiliation

^[1] Univ Fed Minas Gerais, Fac Farm, Av Antonio Carlos 6627, 2nd Floor, Room 2031, BR-31270901 Belo Horizonte, MG - Brazil

^[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, BR-31270901 Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: Journal of Venomous Animals and Toxins including Tropical Diseases; v. 24, NOV 21 2018.
• Web of Science Citations: 1

Abstract

Background: The great diversity of molecules found in spider venoms include amino acids, polyamines, proteins and peptides, among others. Some of these compounds can interact with different neuronal receptors and ion channels including those present in the ocular system. To study potential toxicity and safety of intravitreal injection in rabbits of LyeTx I b, a synthetic peptide derived from the toxin LyeTx I found in venom from the spider Lycosa eritrognatha and to evaluate the angiogenic activity on a CAM model. Methods: ARPE-19 cells were treated with LyeTx I b (0.36; 0.54; 0.72; 2.89; 4.34 or 9.06 mu M). In this study, New Zealand rabbits were used. LyeTx I b (2.89 mu M) labeled with FITC dissolved in PBS, or only PBS, were injected into vitreous humor. Electroretinogram (ERG) was recorded 1 day before injection and at 7, 14 and 28 days post-injection. Clinical examination of the retina was conducted through tonometer and eye fundus after ERG. Eyes were enucleated and retinas were prepared for histology in order to assess retinal structure. CAMs were exposed to LyeTx I b (0.54; 0.72; 2.17 or 2.89 mu M). Results: ARPE-19 cells exposed to LyeTx I b showed cell viability at the same levels of the control. The fluorescence of LyeTx I b labeled with FITC indicated its retinal localization. Our findings indicate ERG responses from rats injected in the eye with LyeTx I b were very similar to the corresponding responses of those animals injected only with vehicle. Clinical examination found no alterations of intraocular pressure or retinal integrity. No histological damage in retinal layers was observed. CAM presented reduced neovascularization when exposed to LyeTx I b. Conclusions: Intravitreal injection of LyeTx I b is safe for use in the rabbit eye and prevents neovascularization in the CAM model, at Bevacizumab levels. These findings support intravitreal LyeTx I b as a good candidate to develop future alternative treatment for the retina in neovascularization diseases. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants