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Abstract

Glaucoma is the main cause of irreversible blindness. Despite reaching the target level of intraocular pressure (IOP), glaucoma often progresses. This highlights the urgent need for therapy aimed directly at protecting the optic nerve. This study presents the development and comprehensive preclinical evaluation of a novel drug, NEUROSTAT-NP – a dry intranasal powder for direct neuroprotection. The active ingredient, bromocriptine mesylate at an ultra-low dose of 0.3 mg, selectively activates dopamine D₂ receptors and the intracellular JAK/STAT pathway in retinal ganglion cells, suppressing apoptosis. The study, conducted on 90 Long-Evans rats, comprised two blocks: a safety assessment (7-day course) and an efficacy evaluation in a chronic glaucoma model (8 weeks). The drug demonstrated an excellent safety profile: biochemical parameters (ALT, AST, creatinine) and organ histology showed no difference from controls, with only mild local hyperemia observed in 1 out of 6 animals. In the simulated glaucoma model, monotherapy with NEUROSTAT-NP, without lowering IOP (which remained at 19.2 ± 1.0 mm Hg), preserved 69% of the retinal ganglion cell population and 64% of functional activity (pERG; p < 0.05). This was significantly higher than the untreated group (46% and 38%, respectively) and comparable to the results of standard hypotensive therapy with latanoprost (76% and 72%). Combined application demonstrated synergy, increasing cell survival to 88% and function to 82%. Thus, NEUROSTAT-NP represents the first safe and effective intranasal neuroprotector whose action is independent of IOP, opening the door to novel adjuvant glaucoma treatment strategies‎.

Keywords: Glaucoma, Neuroprotection, Intranasal delivery, Bromocriptine, JAK/STAT signaling pathway, Experimental model

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