PAC1 receptor agonist maxadilan alleviates corneal edema and inflammation in LPS-induced murine model

Ocular inflammation, including endogenous endophthalmitis stemming from systemic bacterial infections, is a major global cause of visual impairment and blindness. These conditions pose significant diagnostic and therapeutic challenges due to their systemic origin and impact on multiple ocular structures like the retina and cornea. Current treatments often fall short, highlighting a need for novel anti-inflammatory strategies. Pituitary adenylate cyclase-activating polypeptide (PACAP), acting through its selective PAC1 receptor, has demonstrated potent anti-inflammatory, anti-edema, and regenerative effects in various ocular pathologies, making PAC1 activation a promising therapeutic target.

Researchers investigated the protective role of maxadilan, a selective PAC1 receptor agonist, in a mouse model of lipopolysaccharide (LPS)-induced ocular inflammation. Mice received systemic LPS injections to induce inflammation, followed by intravitreal administration of maxadilan. The study design did not specify the exact dose of maxadilan or the number of animals (n). Animals were monitored in vivo using optical coherence tomography (OCT) for corneal structure and tonometry for intraocular pressure. Post-mortem analyses included cytokine expression profiling and routine corneal histological assessment to evaluate inflammatory markers and tissue integrity.

Maxadilan administration significantly mitigated key inflammatory markers and structural damage in the murine model. OCT imaging revealed significantly reduced corneal edema and improved tissue structure in the maxadilan-treated group compared to controls. Additionally, maxadilan lowered intraocular pressure and reduced inflammatory cell infiltration into the aqueous humor. Cytokine profiling demonstrated decreased expression of critical pro-inflammatory mediators, including GM-CSF, IL-6, MIP-1a, TNF-a, and TREM-1, in the maxadilan-treated animals. Histological analyses further confirmed the protective effects: maxadilan preserved normal corneal architecture and effectively prevented pathological keratinization. These findings collectively underscore the potent anti-inflammatory and tissue-protective capabilities of PAC1 receptor activation.

Maxadilan significantly reduced corneal edema and improved tissue structure, while also lowering intraocular pressure and decreasing multiple pro-inflammatory cytokines.