Purpose This study aimed to assess the therapeutic efficacy and safety pharmacology of human keratinocyte growth factor-2 (hKGF-2) eye drops for dry eye disease (DED). Methods We assessed the primary pharmacodynamics of hKGF-2 in two animal models of DED: the benzalkonium chloride (BAC)-induced rabbit model and the scopolamine (SCOP)-induced rat model. Three different doses of hKGF-2 eye drops were administered topically and compared with two commercially available medicines as positive controls, including sodium hyaluronate (SH) eye drops and bovine basic fibroblast growth factor (bFGF) eye drops. The primary endpoints included tear secretion measurement, corneal fluorescein staining (CFS), tear film break-up time (TBUT), and histopathologic examination. For the safety pharmacology studies, the effects on the central nervous system (CNS) were determined using the functional observation battery (FOB) in rats. Additionally, the impacts on the cardiovascular and respiratory systems were analyzed in Beagle dogs by monitoring electrocardiogram (ECG), respiration (RESP), and blood pressure (BP). Results Following 21 days of treatment, all topical hKGF-2 dosage groups (50, 100, 200 μg/mL) showed significant therapeutic effects, which were as effective as the bFGF and SH eye drops. The minimum effective dose (MED) of hKGF-2 in this study was 50 μg/mL. These therapeutic benefits included enhancing basal tear secretion and tear film stability, mitigating corneal damage, and promoting the recovery of corneal thickness as well as the restoration of conjunctival goblet cell counts. In safety pharmacology assessments, FOB results demonstrated that hKGF-2 treatment (20, 50, 100 μg per animal) had no adverse effects on the CNS of rats. Meanwhile, topical administration of hKGF-2 (160, 400, 800 μg per dog) did not elicit any adverse reactions in the cardiovascular or respiratory systems of beagles. Conclusion Topical administration of hKGF-2 effectively ameliorated DED symptoms without adverse effects on the CNS, cardiovascular, and respiratory systems. These results indicated that hKGF-2 eye drops have potential as a safe and effective treatment for DED, and provided reliable preclinical evidence for its subsequent clinical trials and translational application.
Li et al. (Wed,) studied this question.