Topical ocular GLP-1 (FNP120) administration preserves retinal function and morphology in a retinitis pigmentosa mouse model

Abstract

Purpose : Photoreceptor cell degeneration, inflammation, and oxidative stress are commonly associated with retinitis pigmentosa (RP), a retinal degenerative disease. Glucagon-like peptide-1 (GLP-1) is an endogenous neuropeptide synthesized by the retina that has exhibited neuroprotective effects in diabetic retinopathy. Therefore, this work aimed to evaluate a possible neuroprotective effect of a novel GLP-1 eye drop formulation (FNP120) in a mouse model of RP.

Methods : Rd10 mice were used as a model of RP. Topical ocular treatment with GLP-1 or vehicle was administered to rd10 mice from postnatal day 16 to P25 twice a day as eye drops in both eyes (5µL/eye). Three GLP-1 concentrations were tested (1, 2, and 4 mg/mL). Optomotor test and scotopic electroretinography (ERG) were used to evaluate mice retinal function after the treatment. Secondly, retinal cryostat cross-sections were performed to quantify the number of photoreceptor rows throughout the retina. Retinal morphology was analyzed using immunohistochemistry.

Results : Retinal function improved after 10-days of GLP-1 topical ocular administration. Rd10 mice treated with GLP-1 eye drops at a concentration of 2 mg/mL displayed significantly higher scotopic a- and b-wave amplitudes compared to vehicle-treated mice. Optomotor test also showed higher visual acuity found in 2 mg/mL treated rd10 mice. These functional findings correlated with a higher number of photoreceptor rows found in GLP-1 treated rd10 mice retinas. Also, these photoreceptors showed slightly better-preserved morphology and longer outer segments. GLP-1 administered at a concentration of 1 or 4 mg/mL did not achieve significant protective effects.

Conclusions : Topical administration of GLP-1 at 2 mg/mL was able to preserve retinal function loss and photoreceptor cells surviving in the retina of rd10 mice. These data support the view that GLP-1 may emerge as a new therapeutic strategy against retinal neurodegenerative diseases.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.