| Daniel Biros, D.V.M.
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Chronic, uncontrolled uveitis often leads
to intraocular adhesions and irreversible retinal damage.
The long-term objective of my research is to reestablish ocular
immune privilege to the uveitic eye by reimposing expression
of the immunomodulating factor alpha-melanocyte stimulating
hormone (a-MSH) in the ocular microenvironment. It has been
shown that the normal but not uveitic aqueous humor contains
a-MSH and other factors which are known to suppress immunogenic
inflammation. The first specific aim of my research studies
the effects of a-MSH injected into eyes of mice with experimental
autoimmune uveitis (EAU). Experiments have been designed to
monitor the clinical course of disease as well as objectively
evaluate histopathology of treated and untreated tissue. Cytokine
assays of treated and untreated aqueous humor, immunohistochemistry,
and experiments testing for immunosuppressive activity of
aqueous humor of treated mice will also characterize the effects
of local a-MSH injections. The second aim of my research examines
the effects of the gene encoding a-MSH transfected into uveitic
eyes. Viral and non-viral vectors encoding the gene for a-MSH
will be tested. Preliminary data suggest that subconjunctival
injections of naked DNA plasmid vectors expressing a-MSH suppress
the severity and incidence of EAU. This aim involves experiments
demonstrating suppression of EAU following vector transfection.
Aqueous humor from transfected eyes will be characterized
to show reexpression of immunosuppressive factors by cytokine
analysis and aqueous humor suppression of activated T cells
in vitro. Confirmation of transfection will be accomplished
by fluorescent microscopy of ocular tissue transfected with
vectors labeled with GFP. Clinical disease monitoring and
ocular histopathology will also be examined. Discovering specific
effects of a-MSH on EAU will assist in identifying its role
in restoration of ocular immune privilege and expand on the
basic knowledge in the field of gene therapy.
Publications
Biros DJ, Brooks DE, Brown MP, Merritt
KA, Kubilis PS.Regional and Zonal Variations in the Sulfation
Patterns of Chondroitin Sulfate in the Normal Equine Corneal
Stroma. American Journal of Veterinary Research.
2002;63:143-147.
Gelatt KN, van der Woerdt A, Ketring KL,
Andrew SE, Brooks DE, Biros DJ, Denis DM, Cutler TJ. Enrofloxacin-associated
retinal degeneration in cats. Veterinary Ophthalmology.
2001;4:2 99-106.
Brooks DE, Andrew SE, Biros DJ, Denis HM,
Cutler TJ, Strubbe DT, Gelatt KN.Ulcerative keratitis caused
by beta-hemolytic Streptococcus in eleven horses. Veterinary
Ophthalmology. 2000;3:121-126.
Andrew SE, Brooks DE, Biros DJ, Denis HM,
Cutler TJ, Gelatt KN. Posterior lamellar keratoplasty for
treatment of deep stromal abscesses in nine horses. Veterinary
Ophthalmology. 2000;3:99-104.
Brooks DE, Andrew SE, Denis HM, Strubbe
DT, Biros DJ, Cutler TJ, Samuelson DA, Gelatt KN. Rose Bengal
positive epithelial microerosions as a manifestation of equine
keratomycosis. Veterinary Ophthalmology. 2000;3:
83-86.
Cutler TJ, Brooks DE, Andrew SE, Denis HM,
Biros DJ, Gelatt KN, Kom–romy AM, Kållberg M. Disease of the
equine posterior segment. Veterinary Ophthalmology.
2000;3:73-82.
Biros DJ, Gelatt KN, Brooks DE, Kubilis
PS, Andrew SE, Strubbe DT, Whigham HM. Development of glaucoma
after cataract surgery in dogs: 220 cases (1987-1998). Journal
of the American Veterinary Medical Association, 2000;
216: 1780-1786.
Whigham HM, Brooks DE, Andrew SE, Gelatt
KN, Strubbe DT, Biros DJ. Treatment of equine glaucoma by
transscleral Nd:YAG laser cytophotocoagulation: a retrospective
study
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