A comparison of the miotic and inflammatory effects of biologically active polypeptides and prostaglandin E 2 on the rabbit eye

Abstract

The ocular effects of some biologically active peptides were studied and compared to those of prostaglandin E 2 (PGE 2) to determine whether the responses of the eye to trauma, characterized by increased intraocular pressure (IOP), the development of anterior chamber flare and partial miosis, might be mediated by such peptides. One to 2 hr after intravitreal injection of 10 μg of PGE 2 into rabbit eyes, ocular hypertension, flare and iridial hyperemia, but only minimal miosis were observed. Maximum miosis developed within 2–3 hr after intravitreal injection of 1·0–100 μg of substance P (SP), SP-octapeptide (SP-8), coherin or eledoisin-related peptide (EDR), while 10–100 μg of vasoactive intestinal polypeptide (VIP), somatostatin or bradykinin (BK) yielded only submaximal miosis and angiotensin II, α-MSH and poly- dl-alanine had little or no miotic effect. None of these peptides caused iridial hyperemia or a cellular invasion of the anterior chamber and only high doses (100 μg) of VIP or BK caused significant increases in the protein concentration of the aqueous humor. Miotic doses of SP, SP-8 or EDR caused a significant increase in IOP in some, but not all, experiments. Thus, PGE 2 can be regarded as a mediator of the ocular irritative response although it may not account for the miosis that is associated with chemical or surgical trauma. However, this autacoid should not be regarded as the mediator of ocular inflammation since it does not elicit a cellular response. In contrast, some polypeptides, particularly SP, SP-8 and EDR are strong miotics and, at least under some circumstances, can act as effective ocular hypertensives, but these peptides do not reproduce any other signs of ocular irritation or inflammation. It is therefore concluded that none of the peptides studied here could, by itself, be the sole mediator of the initial ocular irritative response although some of them may account for the miosis and contribute to the ocular hypertension associated with this response. A combination of some of these peptides together with PGE 2 and/or other PGs may account for all aspects of the ocular irritative response and for most aspects of the ocular inflammatory response.