This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. However, treatments are lacking, particularly for the more common 'dry' form of this disease, which is characterized by progressive atrophy of the macula and loss of visual acuity. The goal of this translational research program is to protect and restore vision in these diseases using cell replacement therapy. We propose to use human embryonic stem cell-derived cell lines to preserve function and to restore photoreceptors and retinal pigment epithelial (RPE) cells in rodent and primate models.
Specific Aim 1 is to culture and characterize four cell types: a) forebrain-derived human neural stem cells, b) human neural stem cells modified to secrete specific neuroprotective factors, including glial derived growth factor, c) human Schwann cells, and d) human embryonic stem cells isolated at multiple developmental stages along the photoreceptor lineage.
Specific Aim 2 is to transplant these cells to the eyes of rodent models with retinal degenerations to test donor cell survival, evidence of functional and morphological rescue and risk of treatment complications.
Specific Aim 3 is to define and optimize the cell delivery procedure, dosage, safety and biodistribution in rhesus monkeys. Normal eyes will be studied first, followed by a test of efficacy in our unique rhesus monkey model of age-related macular degeneration. Successful completion of this research will pave the way towards human clinical trials that could have considerable impact on the clinical outcomes for this major blinding condition.
|Okoye, Afam A; Hansen, Scott G; Vaidya, Mukta et al. (2018) Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound. Nat Med 24:1430-1440|
|Jensen, Jeffrey T; Hanna, Carol; Mishler, Emily et al. (2018) Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons. J Med Primatol 47:40-45|
|Toro, C A; Aylwin, C F; Lomniczi, A (2018) Hypothalamic epigenetics driving female puberty. J Neuroendocrinol 30:e12589|
|Bulgarelli, Daiane L; Ting, Alison Y; Gordon, Brenda J et al. (2018) Development of macaque secondary follicles exposed to neutral red prior to 3-dimensional culture. J Assist Reprod Genet 35:71-79|
|Prola-Netto, Joao; Woods, Mark; Roberts, Victoria H J et al. (2018) Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure. Radiology 286:122-128|
|Moccetti, Federico; Brown, Eran; Xie, Aris et al. (2018) Myocardial Infarction Produces Sustained Proinflammatory Endothelial Activation in Remote Arteries. J Am Coll Cardiol 72:1015-1026|
|Blue, Steven W; Winchell, Andrea J; Kaucher, Amy V et al. (2018) Simultaneous quantitation of multiple contraceptive hormones in human serum by LC-MS/MS. Contraception 97:363-369|
|Jeon, Sookyoung; Li, Qiyao; Rubakhin, Stanislav S et al. (2018) 13C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study. Nutr Res :|
|Slayden, Ov Daniel; Friason, Francis Kathryn E; Bond, Kise Rosen et al. (2018) Hormonal regulation of oviductal glycoprotein 1 (OVGP1; MUC9) in the rhesus macaque cervix. J Med Primatol 47:362-370|
|Dissen, G A; Adachi, K; Lomniczi, A et al. (2017) Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update. Reprod Domest Anim 52 Suppl 2:354-358|
Showing the most recent 10 out of 492 publications