Neurovespina peptide is a promising new neuroprotective agent for retinal cells after ischemia caused by intraocular pressure (IOP) increase, according to research results published in Neuropeptides. 

Researchers sought to evaluate whether Neurovespina peptide — a short peptide isolated from the venom of the social wasp Polybia occidentalis — might induce neuroprotection in retinal cells. Investigators also examined if this peptide demonstrated antiangiogenic effects in the chicken chorioallantoic membrane (CAM).

Investigators included 24 adult male rats in this animal study. They divided the rats into 4 groups and anesthetized and injected them intravitreally with Neurovespina lyophilized and diluted in 10 µl saline: Group 1 received a final concentration of 24 µg/mL, group 2 received a final concentration of 60 µg/mL, and group 3 receive the same volume of sterile saline. Group 4 was the control group. The investigators induced retinal ischemia one day after injection; they euthanized the rats 15 days later and collected tissue for evaluation. 


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Researchers used a- and b-wave amplitudes to measure retinal response after 7 and 15 days, with cones and rods observed at 0.01 cd.s.m−2. The group treated with the vehicle demonstrated a significant decrease in b-wave amplitude after 0.01 cd.m.s-2 luminous stimulus compared with the control group. Groups treated with Neurovespina exhibited no prominent b-wave amplitude reduction at 7 or 15 days (232.6 ± 76 µV and 301.6 ± 22.7 µV in groups 1 and 2, respectively). At 15 days, group 1 experienced a significant reduction (163.4 ± 16.4 µV); group 2 displayed no significant changes (259.1 ± 62.7 µV) compared with the control group. 

After 0.3 cd.m.s-2 luminous stimulus, investigators detected statistical difference only at day 15 in a-wave amplitudes. The vehicle group demonstrated significant reductions compared with the healthy group, (amplitudes of Neurovespina groups 1 and 2 were -258.3 ± 104.5 µV and -337.2 ± 80.5 µV, respectively). 

Investigators conducted a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay to evaluate the protective effect of Neurovespina in apoptosis after retinal ischemia induction. The vehicle group had a “significant” number of TUNEL-positive cells compared with the healthy group whereas groups 1 and 2 demonstrated that Neurovespina peptide inhibited apoptosis in the ganglion cell layer (44.6 ± 1.8  cells/mm and 25.3±1.1 cells/mm for groups 1 and 2, respectively) and inner nuclear layer (112.8 ± 28.2 cells/mm and 47.7 ± 2.2 cells/mm for each group). 

Investigators then used the CAM assay to evaluate the effect of Neurovespina on angiogenesis. Results demonstrated that in the tested concentrations, Neurovespina significantly reduced the vessel area compared with the control group. In group 2, promoted vessel area reduction was similar to that of bevacizumab (26.8% ± 7.3% vs 25.6 % ± 3.5%). Researchers also noted significant changes in lacunarity. 

“In [a] high IOP-induced ocular ischemia model, Neurovespina was able to minimize the reduction of [electroretinography] waves and to preserve retinal layers’ thickness, mainly in the concentration of 60 µg/mL,” the researchers conclude. “Our findings suggest that Neurovespina presents a neuroprotective effect against retinal ischemia and holds great potential for many ocular disease treatments.”

Future studies are in process to evaluate the mechanistic effect of Neurovespina, as well as its intravitreal bioavailability.

Reference

Dourado LFN, Silva CN, Dos Anjos LC, Mortari MR, Silva-Cunha A, Fialho SL. Ischemia-induced retinal injury is attenuated by Neurovespina, a peptide from the venom of the social wasp Polybia occidentalis. Neuropeptides. 2021;85:102113. doi:10.1016/j.npep.2020.102113.