Atropine Sulfate

Myopia is the most common refractive error worldwide and is projected to affect half of the global population by 2050, with high myopia significantly increasing the risk of vision-threatening complications. While multiple genetic, environmental and lifestyle factors contribute to myopia onset and progression, recent findings suggest a role for vasoactive intestinal peptide (VIP) and its receptor VIPR2 in ocular growth regulation. This review summarizes current knowledge about myopia pathogenesis and the diverse factors involved, focusing on the molecular, genetic, pharmacological, and clinical findings regarding VIP/VIPR2 signaling in the eye. Evidence from animal models reveals a complex interaction between VIP and myopia, with VIP agonists/antagonists either protecting from or promoting myopia depending on model and dosage, VIPR2 knockout mice developing spontaneous myopia, and VIP interacting with circadian rhythms and atropine signaling. Genetic association studies have identified both risk and protective VIPR2 haplotypes, with environmental light exposure modulating their effects. Mechanistic studies suggest that VIP regulates choroidal and scleral remodeling, acting in concert with dopaminergic, cholinergic, and retinoic acid pathways. We propose that VIP/VIPR2 is a key modulator of emmetropization and a promising therapeutic target for myopia, though species-specific effects and context-dependency remain to be resolved.

Preclinical evaluation of oximes as antidotes for organophosphorus nerve agent (OPNAs) poisoning is predominantly based on protection ratio of the antidote against lethal doses. Developing protection indexes involves considerable animal distress and, due to the limited precision, requires large animal cohorts. This study aimed to establish an in vivo model for evaluating new therapeutic substances more aligned with the 3R principles that also enables detailed quantification of specific biological effects to better understand the impact of treatment. Anesthetized Sprague-Dawley rats were tracheostomized and connected to a small animal ventilator allowing simultaneous registration of respiratory function. Rats were exposed to 1xLD₅₀ VX or tabun, and progression of poisoning was monitored in real-time through measurements of respiratory resistance (R_RS) over a 30-min period. Additional assessments included clinical symptoms and acetylcholine esterase (AChE) inhibition in blood. Pre-treatment with oxime (obidoxime, HI-6, RS194B) or atropine were used to validate the model. Exposure to OPNAs resulted in rapid increases in R_RS to 250-300 % above baseline. HI-6 and obidoxime were the most effective treatments, mitigating both respiratory and enzymatic effects of OPNA poisoning, while RS194B treatment delayed onset of symptoms but did not fully reverse toxicity. Tabun-inhibited AChE was generally more resistant to reactivation with oximes than VX- inhibited enzymes. The findings indicate that maintaining AChE activity above 15-20 % is sufficient to restore respiratory function and alleviate symptoms to levels comparable to unexposed controls. This study highlights the value of high-sensitivity, real-time monitoring of physiological metrics like respiratory resistance in evaluating novel antidotes for OPNA poisoning.