Sitagliptin eye drops prevent the impairment of retinal neurovascular unit in the new Trpv2 +/- rat model

• Published in: Journal of neuroinflammation 2024-11, Vol.21 (1), p.312-16, Article 312
• Main Authors: Ramos, Hugo, Augustine, Josy, Karan, Burak M, Hernández, Cristina, Stitt, Alan W, Curtis, Tim M, Simó, Rafael
• Format: Article
• Language: English
• Subjects: Animals; Diabetes; Diabetic retinopathy; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - pathology; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Disease Models, Animal; Dosage and administration; DPP-4 inhibitor; Genetically modified mice; Male; Ophthalmic Solutions; Pharmacology, Experimental; Physiological aspects; Prevention; Rats; Rats, Transgenic; Retina - drug effects; Retina - metabolism; Retina - pathology; Retinal diseases; Sitagliptin; Sitagliptin Phosphate - pharmacology; Sitagliptin Phosphate - therapeutic use; Tomography, Optical Coherence; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Trpv2
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-024-03283-5

Impaired function of the retinal neurovascular unit (NVU) is an early event in diabetic retinopathy (DR). It has been previously shown that topical delivery of the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin can protect against diabetes-mediated dysfunction of the retinal NVU in the db/db mouse. The aim of the present study was to examine whether sitagliptin could prevent the DR-like lesions within the NVU of the new non-diabetic model of DR, the Trpv2 knockout rat (Trpv2 ). For that purpose, at 3 months of age, Trpv2 rats were topically treated twice daily for two weeks with sitagliptin or PBS-vehicle eyedrops. Trpv2 rats treated with vehicle served as the control group. Body weight and glycemia were monitored. Optical coherence tomography recordings, fundus images and retinal samples were obtained to evaluate sitagliptin effects. The results revealed that sitagliptin eye drops had no effect on body weight or glycemia. Vehicle-treated Trpv2 rats exhibited retinal thinning and larger diameters of major retinal blood vessels, upregulation of inflammatory factors and oxidative markers, glial activation and formation of acellular capillaries. However, topical administration of sitagliptin significantly prevented all these abnormalities. In conclusion, sitagliptin eye drops exert a protective effect against DR-like lesions in Trpv2 rats. Our results suggest that sitagliptin eye drops carry significant potential to treat not only early-stages of DR but also other diseases with impairment of the NVU unrelated to diabetes.