Damaging Effect of Retrobulbar L‐NAME Application in Rats Counteracted by Stable Gastric Pentadecapeptid BPC 157
Authors: Zlatar Mirna , Kokot Antonio , Vuletic Lovorka Batelja , Kralj Tamara , Drmic Domagoj , Seiwerth Sven , Sikiric Predrag 
Published: November 2023

Aim

In rats, retrobulbar L‐NAME injection produces quickly severe generalized vessel caliber irregularity, leading to moderate to severe atrophic optic disc, poor presentation of the choroidal blood vessels; retinal ischemia and atrophy, and immobile animal behavior. We hypothesize the stable gastric pentadecapeptide BPC 157 as a therapy. BPC 157 already cures ocular tissues. BPC 157 eye drops (ug‐ or ng‐regimen) rescued total debridement of corneal epithelium (Coll Antropol 2005;29(1):321–5), successfully closed perforating corneal incisions in rats (Exp Eye Res 2015;136:9–15), counteracted particular NO‐specific parallel miotic effect of L‐NAME and L‐arginine and atropine‐induced mydriasis in rats and guinea pigs (Eur J Pharmacol 2016;771:211–9). In addition, BPC 157/NO‐relationship is established in various experimental models and species (Curr Pharm Des 2014;20(7):1126–35), providing that it would counteract the damaging effects of retrobulbar NOS‐blockade and L‐NAME application.

Materials and methods

Female Wistar rats, 200g, randomly assigned, were treated retrobulbary with: L‐NAME (0.1ml/0.2mg/eye) and (a) BPC 157 (0.1ml/0.2μg/eye 20 minutes after L‐NAME application); L‐NAME (0.1ml/0.2mg/eye) and BPC 157 (0.1ml/0.2ng/eye 20 minutes after L‐NAME); L‐NAME (0.1ml/0.2 mg/eye) and 0.9% NaCl (0.1ml/eye 20 minutes after L‐NAME appilication), or altenatively, (b) BPC 157 (0.1ml/0.2μg/eye 48 hours after L‐NAME application); or 0.9% NaCl (0.1ml/eye 48 hours after L‐NAME appilication). Control (sham) animals simultaneously received retrobulbar equivolume of 0.9% NaCl.

With a USB microscope camera “Veho discovery VMS‐004 deluxe” and “VOLK” digital wide field loupe for indirect ophthalmoscopy eye fundus was recorded in the following time periods: before retrobulbar application of L‐NAME (or 0.9% NaCl); 20 minutes after L‐NAME (or 0.9% NaCl); again after BPC 157 (or 0.9% NaCl), and 20 minutes after. Furthermore, recording was performed at the post‐application day 1., 2., and 7., 14., 28. (last day, just before the sacrifice).

The fundus were analyzed by photo analysis software and by histopathologic eyeball analysis on standard sections, paraffin embedded and hemalaun‐eosin stained.

The animals behavior was filmed, observing the following parameters: time of immobility (no movement period) and reaction time to viusal stimuli (blue‐green glove).

Results

Interestingly, given either shortly after L‐NAME, or, alternatively, two days later, retrobulbar application of BPC 157 leads to retinal ischemia recovery, prevents its atrophy and restors normal animal behavior (Figure 1, Figure 2).

Conclusion

BPC 157 was originally an anti‐ulcer peptide used in trials for ulcerative colitis and now is in trials for the treatment of multiple sclerosis that largely interacts with NO‐system (Curr Pharm Des. 2014;20(7):1126–35). Thereby, the noted damaging effect of retrobulbar application L‐NAME in rats that was counteracted by pentadecapeptide BPC 157, provides a particular promissing base for further research and application.

Support or Funding Information

Ministry of Science, Education and Sports, Republic of Croatia (grant 108‐1083570‐3635)