Ocular penetration of anti-herpes simplex virus type 1 anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in an animal model

T. P. O'Brien, T. K. Chan, K. B. Kim, S. A. Kipp, S. A. Lesko, P. S. Miller

Research output: Contribution to journalArticle

Abstract

Purpose. To demonstrate the ocular penetration of anti-herpes simplex virus type 1 (HSV-1) anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in a rabbit model. Previous studies have shown this d-OMP to selectively inhibit HSV-1 replication in virus infected cells. Methods. A 50 μM solution containing a d-OMP whose structure is complementary to the splice junction of HSV-1 immediate early pre-mRNA 4 and 5 was administered topically in rabbit eyes. The d-OMP had been tagged with a fluorescent marker, a BODIPY (bordifluoropyrromethene) derivative. The d-OMP was instilled into the NZW rabbit eyes at 5 minute intervals for a total of 3 doses (35 μl per dose). Fellow eyes of rabbits which received only topical saline in a similar fashion, served as controls. Animals were sacrificed at 15 minutes, 30 minutes, and 45 minutes respectively after the first dosing and their corneas removed for frozen section. The frozen sections were then immediately examined under an epifluorescent microscope. Results. A layer of fluorescence was observed in the superficial epithelium as early as 15 minutes after the first dose of d-OMP. This fluorescent layer was still present in the corneal epithelium at 30 minutes. 45 minutes after the first dosing, the penetration of fluorescence had increased, although the total fluorescence appeared less intense and more diffuse in the deeper layers of epithelium. No fluorescence was observed in frozen sections of control eyes. Conclusion. This suggests that d-OMP penetrates fairly rapidly into the rabbit cornea when administered topically. d-OMP at the active site may have a potentially useful role as an antiviral agent for the clinical treatment of herpes simplex epithelial keratitis.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

Fingerprint

Human Herpesvirus 1
Animal Models
Rabbits
Frozen Sections
Fluorescence
Cornea
Epithelium
Herpetic Keratitis
Corneal Epithelium
RNA Precursors
Virus Replication
Antiviral Agents
Catalytic Domain
dideoxyribonucleoside methylphosphonates
Viruses

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Ocular penetration of anti-herpes simplex virus type 1 anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in an animal model. / O'Brien, T. P.; Chan, T. K.; Kim, K. B.; Kipp, S. A.; Lesko, S. A.; Miller, P. S.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996.

Research output: Contribution to journalArticle

@article{7f213afe510941769dd5d02bf870e2a3,
title = "Ocular penetration of anti-herpes simplex virus type 1 anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in an animal model",
abstract = "Purpose. To demonstrate the ocular penetration of anti-herpes simplex virus type 1 (HSV-1) anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in a rabbit model. Previous studies have shown this d-OMP to selectively inhibit HSV-1 replication in virus infected cells. Methods. A 50 μM solution containing a d-OMP whose structure is complementary to the splice junction of HSV-1 immediate early pre-mRNA 4 and 5 was administered topically in rabbit eyes. The d-OMP had been tagged with a fluorescent marker, a BODIPY (bordifluoropyrromethene) derivative. The d-OMP was instilled into the NZW rabbit eyes at 5 minute intervals for a total of 3 doses (35 μl per dose). Fellow eyes of rabbits which received only topical saline in a similar fashion, served as controls. Animals were sacrificed at 15 minutes, 30 minutes, and 45 minutes respectively after the first dosing and their corneas removed for frozen section. The frozen sections were then immediately examined under an epifluorescent microscope. Results. A layer of fluorescence was observed in the superficial epithelium as early as 15 minutes after the first dose of d-OMP. This fluorescent layer was still present in the corneal epithelium at 30 minutes. 45 minutes after the first dosing, the penetration of fluorescence had increased, although the total fluorescence appeared less intense and more diffuse in the deeper layers of epithelium. No fluorescence was observed in frozen sections of control eyes. Conclusion. This suggests that d-OMP penetrates fairly rapidly into the rabbit cornea when administered topically. d-OMP at the active site may have a potentially useful role as an antiviral agent for the clinical treatment of herpes simplex epithelial keratitis.",
author = "O'Brien, {T. P.} and Chan, {T. K.} and Kim, {K. B.} and Kipp, {S. A.} and Lesko, {S. A.} and Miller, {P. S.}",
year = "1996",
month = "2",
day = "15",
language = "English (US)",
volume = "37",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "3",

}

TY - JOUR

T1 - Ocular penetration of anti-herpes simplex virus type 1 anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in an animal model

AU - O'Brien, T. P.

AU - Chan, T. K.

AU - Kim, K. B.

AU - Kipp, S. A.

AU - Lesko, S. A.

AU - Miller, P. S.

PY - 1996/2/15

Y1 - 1996/2/15

N2 - Purpose. To demonstrate the ocular penetration of anti-herpes simplex virus type 1 (HSV-1) anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in a rabbit model. Previous studies have shown this d-OMP to selectively inhibit HSV-1 replication in virus infected cells. Methods. A 50 μM solution containing a d-OMP whose structure is complementary to the splice junction of HSV-1 immediate early pre-mRNA 4 and 5 was administered topically in rabbit eyes. The d-OMP had been tagged with a fluorescent marker, a BODIPY (bordifluoropyrromethene) derivative. The d-OMP was instilled into the NZW rabbit eyes at 5 minute intervals for a total of 3 doses (35 μl per dose). Fellow eyes of rabbits which received only topical saline in a similar fashion, served as controls. Animals were sacrificed at 15 minutes, 30 minutes, and 45 minutes respectively after the first dosing and their corneas removed for frozen section. The frozen sections were then immediately examined under an epifluorescent microscope. Results. A layer of fluorescence was observed in the superficial epithelium as early as 15 minutes after the first dose of d-OMP. This fluorescent layer was still present in the corneal epithelium at 30 minutes. 45 minutes after the first dosing, the penetration of fluorescence had increased, although the total fluorescence appeared less intense and more diffuse in the deeper layers of epithelium. No fluorescence was observed in frozen sections of control eyes. Conclusion. This suggests that d-OMP penetrates fairly rapidly into the rabbit cornea when administered topically. d-OMP at the active site may have a potentially useful role as an antiviral agent for the clinical treatment of herpes simplex epithelial keratitis.

AB - Purpose. To demonstrate the ocular penetration of anti-herpes simplex virus type 1 (HSV-1) anticode oligodeoxyribonucleoside methylphosphonate (d-OMP) in a rabbit model. Previous studies have shown this d-OMP to selectively inhibit HSV-1 replication in virus infected cells. Methods. A 50 μM solution containing a d-OMP whose structure is complementary to the splice junction of HSV-1 immediate early pre-mRNA 4 and 5 was administered topically in rabbit eyes. The d-OMP had been tagged with a fluorescent marker, a BODIPY (bordifluoropyrromethene) derivative. The d-OMP was instilled into the NZW rabbit eyes at 5 minute intervals for a total of 3 doses (35 μl per dose). Fellow eyes of rabbits which received only topical saline in a similar fashion, served as controls. Animals were sacrificed at 15 minutes, 30 minutes, and 45 minutes respectively after the first dosing and their corneas removed for frozen section. The frozen sections were then immediately examined under an epifluorescent microscope. Results. A layer of fluorescence was observed in the superficial epithelium as early as 15 minutes after the first dose of d-OMP. This fluorescent layer was still present in the corneal epithelium at 30 minutes. 45 minutes after the first dosing, the penetration of fluorescence had increased, although the total fluorescence appeared less intense and more diffuse in the deeper layers of epithelium. No fluorescence was observed in frozen sections of control eyes. Conclusion. This suggests that d-OMP penetrates fairly rapidly into the rabbit cornea when administered topically. d-OMP at the active site may have a potentially useful role as an antiviral agent for the clinical treatment of herpes simplex epithelial keratitis.

UR - http://www.scopus.com/inward/record.url?scp=33750191951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750191951&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33750191951

VL - 37

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 3

ER -