In the 21st century, adenovirus (Ad) ocular infections remain a significant worldwide problem for which there are no antiviral treatment options. One long term objective is to develop an effective topical antiviral to treat adenoviral ocular infections. In this competing renewal, we will evaluate several promising antivirals (ddC, NCT, CPE-C) in vitro and in our rabbit ocular model and determine the best candidate for clinical development. The issue of emerging resistance to candidate antivirals will be addressed and the possibility of clinically-significant cross resistance among antivirals will be assessed following the determination of their respective molecular mechanisn(s) of inhibitory action. Finally, we will characterize the role of local innate immunity that initially protects the eye from infection by adenovirus. Specifically, we will evaluate the role of defensin-like compounds including alpha and beta defensins, defensin-like chemokines (CXCL 10 and CXCL 11), and cathelicidins. The results of these pathogenesis studies will advance our knowledge of how adenovirus overcomes host defenses to successfully establish eye infections. In summary, the development of an effective antiviral treatment should lessen patient misery, limit epidemics, and reduce economic, educational and other societal losses from absenteeism. Furthermore, a better understanding of antiviral resistance and the innate immune host defenses will enable us to optimize our therapeutic options against this significant ocular pathogen.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-VISA (01))
Program Officer
Shen, Grace L
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University of Pittsburgh
Schools of Medicine
United States
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Kowalski, Regis P; Romanowski, Eric G; Mah, Francis S et al. (2010) Topical levofloxacin 1.5% overcomes in vitro resistance in rabbit keratitis models. Acta Ophthalmol 88:e120-5
Gordon, Y Jerold; Romanowski, Eric G; Shanks, Robert M Q et al. (2009) CAP37-derived antimicrobial peptides have in vitro antiviral activity against adenovirus and herpes simplex virus type 1. Curr Eye Res 34:241-9
Romanowski, Eric G; Yates, Kathleen A; Gordon, Y Jerold (2009) The in vitro and in vivo evaluation of ddC as a topical antiviral for ocular adenovirus infections. Invest Ophthalmol Vis Sci 50:5295-9
Nwanegbo, Edward C; Romanowski, Eric G; Gordon, Y Jerold et al. (2007) Efficacy of topical immunoglobulins against experimental adenoviral ocular infection. Invest Ophthalmol Vis Sci 48:4171-6
Romanowski, Eric G; Yates, Kathleen A; Teuchner, Barbara et al. (2006) N-chlorotaurine is an effective antiviral agent against adenovirus in vitro and in the Ad5/NZW rabbit ocular model. Invest Ophthalmol Vis Sci 47:2021-6
Gordon, Y Jerold; Romanowski, Eric G; McDermott, Alison M (2005) A review of antimicrobial peptides and their therapeutic potential as anti-infective drugs. Curr Eye Res 30:505-15
Romanowski, Eric G; Pless, Patricia; Yates, Kathleen A et al. (2005) Topical cyclosporine A inhibits subepithelial immune infiltrates but also promotes viral shedding in experimental adenovirus models. Cornea 24:86-91
Harvey, Stephen A K; Romanowski, Eric G; Yates, Kathleen A et al. (2005) Adenovirus-directed ocular innate immunity: the role of conjunctival defensin-like chemokines (IP-10, I-TAC) and phagocytic human defensin-alpha. Invest Ophthalmol Vis Sci 46:3657-65
Kinchington, Paul R; Romanowski, Eric G; Jerold Gordon, Y (2005) Prospects for adenovirus antivirals. J Antimicrob Chemother 55:424-9
Gordon, Y Jerold; Huang, Ling C; Romanowski, Eric G et al. (2005) Human cathelicidin (LL-37), a multifunctional peptide, is expressed by ocular surface epithelia and has potent antibacterial and antiviral activity. Curr Eye Res 30:385-94

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