Topical Porphyrin Antioxidant Protects Against Ocular Surface Pathology in a Novel Rabbit Model for Particulate Matter-Induced Dry Eye Disease.
J Ocul Pharmacol Ther
; 38(4): 294-304, 2022 05.
Article
en En
| MEDLINE
| ID: mdl-35384749
ABSTRACT
Purpose:
Particulate matter (PM) is a primary cause for the development of acute and chronic dry eye disease, especially irritant-induced conjunctivitis. The purpose of the present study was to determine the effects of fine atmospheric PM on the rabbit ocular surface, and determine the protective effects of a synthetic antioxidant, manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin (Mn-TM-2-PyP), in vitro and in vivo.Methods:
Rabbit corneal epithelial cells (SIRC) were exposed to increasing concentrations of PM to determine the effects on cell motility and viability. The in vivo effects of topically instilled PM were tested in New Zealand White rabbits. Comprehensive ophthalmic exams and corneal fluorescein staining were performed.Results:
Exposure to PM resulted in dose-dependent cell death and impaired cellular motility; Mn-TM-2-PyP protected against PM-induced cytotoxicity and significantly increased SIRC cell motility. In vivo, exposure to PM (5 mg/ml, topical, 3 times daily for 7 days) resulted in signs of dry eye, notably hyperemia, increased corneal fluorescein staining, and decreased tear volumes. Mn-TM-2-PyP significantly improved hyperemia and corneal fluorescein readouts but had no effect on tear production. Lifitegrast (Xiidra®) showed similar pharmacologic efficacy to Mn-TM-2-PyP.Conclusion:
Overall, these data provide evidence that PM induces phenotypes of ocular surface disease responsive to antioxidant and immunosuppressant therapy. To our knowledge this is the first report of a large animal model to study PM-induced ocular surface disease. The present work provides standardized experimental paradigms for the comprehensive in vitro and in vivo testing of novel therapeutic approaches targeting PM-induced conjunctivitis and dry-eye.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Porfirinas
/
Síndromes de Ojo Seco
/
Conjuntivitis
/
Hiperemia
Límite:
Animals
Idioma:
En
Revista:
J Ocul Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
OFTALMOLOGIA
/
TERAPEUTICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos