Effective treatment of ocular HSK with a human apolipoprotein E mimetic peptide in a mouse eye model.
OBJECTIVE
To evaluate efficacy of the small apolipoprotein E (apoE) mimetic dimer peptide (apoEdp) in the treatment of herpetic stromal keratitis in a mouse ocular model and determine its therapeutic effects against HSV-1-induced inflammatory cytokines.


METHODS
Female C57Bl/6 mice were corneally infected with HSV-1 strain KOS-GFP; topical treatment was initiated 24 hours after infection and continued for 10 consecutive days. Treatment groups were 1% apoEdp, 1% trifluorothymidine (TFT), and phosphate-buffered saline (PBS). The incidence and severity of stromal keratitis were monitored by slit lamp examination in a masked fashion. Infectious HSV-1 titer in eye swabs and alteration in inflammatory cytokines were determined in the early postinfection period by real-time RT-PCR.


RESULTS
One percent apoEdp treatment, which significantly reduced the incidence and severity of HSK, was equal to the effect of 1% TFT; both groups had significantly lower incidence and severity than the placebo treatment group. The in vivo mouse ocular model results of apoEdp therapy correlated with accelerated clearance of virus from eye swabs. Topical 1% apoEdp treatment in mice significantly downregulated gene expression of mouse proinflammatory cytokines.


CONCLUSIONS
These results suggest that topical treatment with apoE peptide has efficacy against HSK through anti-HSV-1 and anti-inflammatory activities.
Departments of Ophthalmology, School of Public Health, LouisianaState University Health Sciences Center, New Orleans, Louisiana 70112, USA. pbhatt@lsuhsc.edu
Partha S
PS
Bhattacharjee
Donna M
DM
Neumann
Timothy P
TP
Foster
Christian
C
Clement
Gyanendra
G
Singh
Hilary W
HW
Thompson
Herbert E
HE
Kaufman
James M
JM
Hill
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000737:chemistry / Q000627:therapeutic use*; D003319:Corneal Stroma / Q000378:metabolism / Q000821:virology*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000302:isolation & purification; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014271:Trifluridine / Q000627:therapeutic use
D000998:Antiviral Agents; D001057:Apolipoproteins E; D016207:Cytokines; D010446:Peptide Fragments; D012333:RNA, Messenger; D014271:Trifluridine