A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study.

Animals Cornea Corneal Diseases Corneal Edema Mustard Gas / toxicity Pilot Projects Rabbits
cornea corneal edema intraocular pressure ocular inflammation sulfur mustard

Journal

Translational vision science & technology
ISSN: 2164-2591
Titre abrégé: Transl Vis Sci Technol
Pays: United States
ID NLM: 101595919

Informations de publication

Date de publication:
11 2020
Historique:
received: 16 07 2020
accepted: 09 09 2020
entrez: 17 11 2020
pubmed: 18 11 2020
medline: 18 11 2020
Statut: epublish

Résumé

This pilot study investigated the in vivo therapeutic potential and tolerability of a multimodal ophthalmic formulation, topical eye drops (TED), for acute mustard gas keratopathy (MGK) using a rabbit model. Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD]) received single sulfur mustard gas (SM) vapor injury, whereas contralateral eyes were left untreated or received TED for tolerabilty evaluation. Two rabbit eyes received no treatment and served as age-matched naive control. The four groups were: Naive (oculus sinister [OS] untreated eyes; n = 9); TED (OS treated only with TED BID for 3 days; n = 9); SM (OD exposed to SM vapor; n = 9); and SM+TED (OD exposed to SM+TED BID for 3 days; n = 9). Ocular examination in live rabbits were performed utilizing slit-lamp biomicroscopy, Fantes grading system, fluorescein staining, Schirmer's tests, pachymetry, and applanation tonometry. Cellular and molecular changes in rabbit corneas were assessed after humane euthanasia on day-3 and day-7 with histopathological and real-time polymerase chain reaction PCR techniques. TED to rabbit eyes was found tolerable in vivo. SM-exposed eyes showed significant increase in Fantes scores, central corneal thickness (CCT), Schirmer's test, epithelium-stroma separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer's test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factor-TGF-β1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity. The developed multimodal eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo. TED is effective against MGK.

Identifiants

DOI: 10.1167/tvst.9.12.6 PMID: 33200047 PMC: PMC7645241
pubmed: 33200047
doi: 10.1167/tvst.9.12.6
pii: TVST-20-2844
pmc: PMC7645241
doi:

Substances chimiques

Mustard Gas T8KEC9FH9P

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Pagination

6

Subventions

Organisme : NEI NIH HHS
ID : R01 EY030774
Pays : United States
Organisme : BLRD VA
ID : IK6 BX005646
Pays : United States
Organisme : NEI NIH HHS
ID : U01 EY031650
Pays : United States
Organisme : BLRD VA
ID : I01 BX000357
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY017294
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY030234
Pays : United States

Informations de copyright

Copyright 2020 The Authors.

Déclaration de conflit d'intérêts

Disclosure: R. Tripathi, None; P.K. Balne, None; N.R. Sinha, None; L.M. Martin, None; S. Kamil, None; J.R. Landreneau, None; S. Gupta, None; J.T. Rodier, None; P.R. Sinha, None; N.P. Hesemann, None; A.C. Hofmann, None; M.K. Fink, None; S.S. Chaurasia, None; R.R. Mohan, None

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Auteurs

Ratnakar Tripathi (R)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Praveen K Balne (PK)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Nishant R Sinha (NR)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Lynn M Martin (LM)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Sabeeh Kamil (S)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

James R Landreneau (JR)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA.

Suneel Gupta (S)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Jason T Rodier (JT)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA.

Prashant R Sinha (PR)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Nathan P Hesemann (NP)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA.

Alexandria C Hofmann (AC)

One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA.

Michael K Fink (MK)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Shyam S Chaurasia (SS)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.

Rajiv R Mohan (RR)

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.
One-Health Vision Research Program, Departments of Veterinary Medicine and Surgery and Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA.

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