The study investigated effectiveness of a novel PEDF peptide mimetic to alleviate dry eye-like pathologies in a Type I diabetic mouse model established using streptozotocin. Mice were treated topically for 3–6 weeks with Ppx (a 17-mer PEDF mimetic) 2x/day or vehicle. Corneal sensitivity, tear film, epithelial and endothelial injury were measured using Cochet-Bonnet esthesiometer, phenol red cotton thread wetting, fluorescein sodium staining, and ZO1 expression, respectively. Inflammatory and parasympathetic nerve markers and activation of the MAPK/JNK pathways in the lacrimal glands were measured. Diabetic mice exhibited features of dry eye including reduced corneal sensation and tear secretion and increased corneal epithelium injury, nerve degeneration, and edema. Ppx reversed these pathologies and restored ZO1 expression and morphological integrity of the endothelium. Upregulation of IL-1β and TNFα, increased activation of P-38, JNK, and ERK, and higher levels of M3ACHR in diabetic lacrimal glands were also reversed by the peptide treatment. The study demonstrates that topical application of a synthetic PEDF mimetic effectively alleviates diabetes-induced dry eye by restoring corneal sensitivity, tear secretion, and endothelial barrier and lacrimal gland function. These findings have significant implications for the potential treatment of dry eye using a cost-effective and reproducible approach with minimal invasiveness and no obvious side effects.

中文翻译：

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PEDF 肽模拟物通过恢复角膜神经、屏障和泪腺功能，有效缓解糖尿病小鼠模型中的干眼症

该研究调查了新型 PEDF 肽模拟物在使用链脲佐菌素建立的 I 型糖尿病小鼠模型中缓解干眼样病变的有效性。使用 Ppx（一种 17 聚体 PEDF 模拟物）每天 2 次或媒介物对小鼠进行局部治疗 3-6 周。分别使用Cochet-Bonnet感觉计、酚红棉线润湿、荧光素钠染色和ZO1表达来测量角膜敏感性、泪膜、上皮和内皮损伤。测量炎症和副交感神经标记物以及泪腺中 MAPK/JNK 通路的激活。糖尿病小鼠表现出干眼的特征，包括角膜感觉和泪液分泌减少以及角膜上皮损伤、神经变性和水肿增加。 Ppx 逆转了这些病理并恢复了 ZO1 表达和内皮细胞形态完整性。肽治疗还逆转了糖尿病泪腺中 IL-1β 和 TNFα 的上调、P-38、JNK 和 ERK 激活的增加以及 M3ACHR 水平的升高。该研究表明，局部应用合成 PEDF 模拟物可通过恢复角膜敏感性、泪液分泌以及内皮屏障和泪腺功能，有效缓解糖尿病引起的干眼症。这些发现对于使用经济有效、可重复、侵入性最小且无明显副作用的方法治疗干眼具有重要意义。