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

Abstract

BackgroundThe 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.MethodsARPE-19 cells were treated with LyeTx I b (0.36; 0.54; 0.72; 2.89; 4.34 or 9.06 μM). In this study, New Zealand rabbits were used. LyeTx I b (2.89 μM) 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 μM).ResultsARPE-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.ConclusionsIntravitreal 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.

Intravitreal injection of peptides PnPa11 and PnPa13, derivatives of Phoneutria nigriventer spider venom, prevents retinal damage

“…ARPE-19 cells are present in many in vitro protocols that involve the investigation of ocular diseases [25,35]. In our study, we demonstrated that PnPa11 or PnPa13, within the range of tested concentration did not promote significant cytotoxic effects, indicating their safety for retina cells.…”

A New Topical Eye Drop Containing LyeTxI-b, A Synthetic Peptide Designed from A Lycosa erithrognata Venom Toxin, Was Effective to Treat Resistant Bacterial Keratitis

“…Immediately after sacrifice, one part of the cornea was removed and fixed in Davidson solution [16]. Samples were included in paraffin and 4-μm-thick sections of the sagittal plane, to allow dorsal-to-ventral observation of the cornea and retina, were stained with hematoxylin and eosin and were analyzed in unmyelinated areas under light microscopy (Zeiss ® , Model Axio Imager M2, San Diego, California, USA).…”

“…It was very effective in treating in vivo septic arthritis in a mouse model [15]. In addition, this synthetic peptide was not toxic to rabbits’ eyes after intravitreal injection and was able to prevent neovascularization in the chorioallantoic membrane, at Bevacizumab levels [16]. Thus, the main goal of this work was to check the effectiveness of LyeTxI-b to the treat in vivo resistant S. aureus keratitis by topical application.…”

LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model

“…LyeTx I-b was active against diverse bacteria in in vitro and in vivo assays [ 35 , 36 , 37 ] and presented a higher affinity in phospholipid membrane assays compared to LyeTx I [ 38 ]. Furthermore, a previous study conducted by our group showed that intraocular injection of LyeTx I-b suppressed neovascularization in ocular disease using a chorioallantoic membrane model [ 39 ]. LyeTxI-b also showed antibacterial activity against resistant keratitis caused by ocular infection with no sign of toxicity [ 40 ].…”