In rats and guinea pigs, the peptide BPC‑157 didn’t change normal pupil size, but it could reduce the eye‑wide dilation caused by atropine and altered how other nitric‑oxide drugs (L‑NAME and L‑arginine) affected pupil size. The effects seem to involve nitric‑oxide and cholinergic pathways, but the study was done only in animals and focused on eye responses.

We revealed an immediate and hours-lasting particular NO-specific parallel miotic effect of L-NAME and L-arginine in rats and guinea pigs and a stable gastric pentadecapeptide BPC 157 157-particular effect vs. that of atropine-induced mydriasis while examining the NO system role in the normal pupils responses and pupils with atropine-induced mydriasis. We also assessed the responses to BPC 157 and its possible modulation of the changes caused by L-NAME/L-arginine and atropine. We administered locally (two drops/eye) or systemically (intraperitoneally/kg) [BPC 157 (0.4µg/eye; 10µg, 10ng, 10pg/kg), L-NAME (0.1mg/eye; 5mg/kg), and L-arginine (2mg/eye; 100mg/kg) alone and combined] at 3min prior to assessment (normal pupils) or alternatively at maximal 1% atropine-induced mydriasis (30min after two drops were administered to each eye). L-NAME/L-arginine. Normal pupil. L-NAME-miosis and L-arginine-miosis shortened and attenuated each other's responses when combined (L-NAME+L-arginine) (except with guinea pigs treated locally) and were thereby NO-specific. Atropine-pupil. Both L-NAME and L-arginine counteracted atropine-induced mydriasis. With few exceptions, the atropine+L-NAME+L-arginine-animals showed a consistent shift toward the left. BPC 157. Normal pupil. Always, BPC 157 alone (both species; locally; systemically; all regimens) did not affect normal pupils. Despite specific exceptions, BPC 157 distinctively affects L-arginine-miosis (prolongation) and L-NAME-miosis (shortening). When L-arginine and L-NAME were combined (L-NAME+L-arginine+BPC 157), the effect was less pronounced. Atropine-pupil. BPC 157 alone counteracted atropine-induced mydriasis. With few exceptions (when administered with L-NAME or L-arginine or L-NAME+L-arginine), BPC 157 augments their counteracting effects. Thus, along with its l-NAME/L-arginine effects, BPC 157 participates in ocular control, potentially via NO-mediated and cholinergic mechanisms.