This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To determine the effects of vitamin D on intraocular pressure (IOP) in monkeys in vivo. To utilize the monkey anterior segment in organ culture (MOCAS) to investigate the effects of gene therapy and other molecules on trabecular outflow which may also be important for glaucoma therapy. Over expression of proteins that alter aqueous humor outflow may lead to intraocular pressure reduction that is important for glaucoma therapy. Alternatively, elevation of intraocular pressure may lead to a new glaucoma model. DESCRIPTION: Monkey eyes in vivo were treated topically with Vitamin D and the effects on IOP were determined. Over-expression of the protein cochlin, which is elevated only in human glaucoma, increases intraocular pressure (IOP) and decreases trabecular outflow. Treatment of MOCAS with TGFb2 induces cochlin production. The role of cochlin in the IOP elevation induced by TGFb2 will be determined by silencing cochlin expression with shRNA for cochlin during TGFb2 treatment. Adeno viral vectors expressing caldesmon or C3 have been shown to decrease IOP in MOCAS. F I V vectors expressing caldesmon or C3 are being tested in MOCAS before injection into monkey eyes in vivo. MOCAS were treated with the HepII domain of fibronectin in order to evaluate the morphology of the trabecular meshwork during IOP reduction. PROGRESS: Topical treatment of monkey eyes in vivo with vitamin D decreases IOP. The mechanism for this effect is under investigation. There does not seem to be any effect on uveoscleral outflow or aqueous humor formation. Treatment of MOCAS with VitD did not have any effect on IOP suggesting trabecular outflow is not affected. MOCAS were treated with H I V vectors expressing shRNA cochlin or the negative control. There was no effect out intraocular pressure or outflow facility of the vectors alone. TGFb2 induced IOP elevation in MOCAS was not consistent enough between paired MOCAS to determine the effects of silencing cochlin expression on TGFb2 induced IOP elevation. Additional experiments will be conducted with adeno vectors over-expressing cochlin. Treatment of MOCAS with F I V vectors expressing caldesmon or C3 did not lower IOP. The possibility that previous results with adeno viral vectors may, in part, be due to augmentation of the caldesmon or C3 response by adeno vector interaction with integrins is being investigated. Cell soluble C3 also did not decrease IOP in MOCAS. The TAT sequence on commercially available C3 may have caused endocytosis into vesicles sequestering the C3 from its target. HepII treatment of MOCAS resulted in expansion of the space between the inner wall of Schlemm's canal and the trabecular collagen beams compared to control. This research used WNPRC Animal and Pathology Services. PUBLICATION: *Schwinn MK, Gonzalez JM Jr, Gabelt BT, Sheibani N, Kaufman PL, Peters DM: Heparin II domain of fibronectin mediates contractility through an alpha4beta1co-signaling pathway. Exp Eye Res, 316:1500-1512, 2010. PMID: 20302860, PMCID2871963.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000167-50
Application #
8358194
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$53,198
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Ellis, Amy; Balgeman, Alexis; Rodgers, Mark et al. (2017) Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques. Infect Immun 85:
Mattison, Julie A; Colman, Ricki J; Beasley, T Mark et al. (2017) Caloric restriction improves health and survival of rhesus monkeys. Nat Commun 8:14063
Buechler, Connor R; Bailey, Adam L; Lauck, Michael et al. (2017) Genome Sequence of a Novel Kunsagivirus (Picornaviridae: Kunsagivirus) from a Wild Baboon (Papio cynocephalus). Genome Announc 5:
Rodrigues, Michelle A (2017) Female Spider Monkeys (Ateles geoffroyi) Cope with Anthropogenic Disturbance Through Fission-Fusion Dynamics. Int J Primatol 38:838-855
Wu, Hong; Whritenour, Jessica; Sanford, Jonathan C et al. (2017) Identification of MHC Haplotypes Associated with Drug-induced Hypersensitivity Reactions in Cynomolgus Monkeys. Toxicol Pathol 45:127-133
Shackman, A J; Fox, A S; Oler, J A et al. (2017) Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology. Mol Psychiatry 22:724-732
Kalin, Ned H (2017) Mechanisms underlying the early risk to develop anxiety and depression: A translational approach. Eur Neuropsychopharmacol 27:543-553
Singaravelu, Janani; Zhao, Lian; Fariss, Robert N et al. (2017) Microglia in the primate macula: specializations in microglial distribution and morphology with retinal position and with aging. Brain Struct Funct 222:2759-2771
Feltovich, Helen (2017) Cervical Evaluation: From Ancient Medicine to Precision Medicine. Obstet Gynecol 130:51-63
Sutton, Matthew S; Burns, Charles M; Weiler, Andrea M et al. (2016) Vaccination with Live Attenuated Simian Immunodeficiency Virus (SIV) Protects from Mucosal, but Not Necessarily Intravenous, Challenge with a Minimally Heterologous SIV. J Virol 90:5541-8

Showing the most recent 10 out of 523 publications