The ocular vascular resistance of the ciliary choroidal network has been investigated on measurements of pulse amplitude(PA). The ocular pulse is derived from the ciliary choroidal blood flow which account for more than 90% of the total ocular blood flow(OBF). In 5 normal Cynomolgus monkeys with topical application(50 micro l) of 2% epinephrine, the PA revealed a significant reduction(0.32 +/- 0.06mmHg, mean +/- SEM, p<0.01). In the other 5 normal Cynormlgus monkeys with 4% pilocarpine, the PA revealed no significant increment(0.32 +/- 0.15mmHg, mean +/- SEM, p<0.10) by the OBF system. These results suggest that topical application of epinephrine produces a significant reduction of OBR but pilocarpine produces a mild increment of OBF.
Choroid ; Epinephrine* ; Haplorhini ; Macaca fascicularis ; Pilocarpine* ; Vascular Resistance

The ocular vascular resistance of the ciliary choroidal network has been investigated on measurements of pulse amplitude(PA). The ocular pulse is derived from the ciliary choroidal blood flow which account for more than 90% of the total ocular blood flow(OBF). In 5 normal Cynomolgus monkeys with topical application(50 micro l) of 2% epinephrine, the PA revealed a significant reduction(0.32 +/- 0.06mmHg, mean +/- SEM, p<0.01). In the other 5 normal Cynormlgus monkeys with 4% pilocarpine, the PA revealed no significant increment(0.32 +/- 0.15mmHg, mean +/- SEM, p<0.10) by the OBF system. These results suggest that topical application of epinephrine produces a significant reduction of OBR but pilocarpine produces a mild increment of OBF.
Choroid ; Epinephrine* ; Haplorhini ; Macaca fascicularis ; Pilocarpine* ; Vascular Resistance

The cholinergic and adrenergic nerve innervation and nerve endings of the iris muscle in Cynomolgus monkey eye is studied by electron microscopy. In the iris, the sphincter muscle reveals nerve terminals containing small empty vesicle which is said to be cholinergic in a greater number (about 85% of nerve terminals) and those containing small cored vericles which is said to be adrenergic in a fewer number (about 15% of nerve terminals) and the latter are more frequently found in the region of peripheral one third of the sphincter muscle then the rest two thirds. In the dilator muscle 65% of the nerve terminals is found to be adrenergic and 35% cholinergic. A dual innervation, adrenergic and cholinergic nerves in both the iris dilator and the sphincter muscle, is not clearly explained in their functions, that is, how influence two nerves one another in addition to the effector cells. A single or double layer of basement membrane lies between the nerve terminals and adjacent muscle in the stromal site of iris muscle. In part the close apposition of the nerve with muscle membrane is seperated by an intercellular space of about 200 A, which is much more in the muscle bundles than in the peripheral portion of the sphincter muscle, however a few in the dilator muscle. The two or three adrenergic and cholinergic axons or terminals in the iris muscle are often closely adjacent to one another, which nerve terminals are not clarified, whether two nerves is motor, or afferent and efferent nerve unit.
Axons ; Basement Membrane ; Extracellular Space ; Haplorhini* ; Iris* ; Macaca fascicularis ; Membranes ; Microscopy, Electron ; Nerve Endings*

BACKGROUND: A crucial limitation of DNA vaccines is its weak immunogenicity, especially in terms of eliciting antibody responses in non-human primates or humans; therefore, it is essential to enhance immune responses to vaccination for the development of successful DNA vaccines for humans. METHODS: Here, we approached this issue by evaluating interleukin-7 (IL-7) as a genetic adjuvant in cynomolgus monkeys immunized with multigenic HCV DNA vaccine. RESULTS: Codelivery of human IL-7 (hIL-7)-encoding DNA appeared to increase DNA vaccine-induced antibody responses specific for HCV E2 protein, which plays a critical role in protecting from HCV infection. HCV-specific T cell responses were also significantly enhanced by codelivery of hIL-7 DNA. Interestingly, the augmentation of T cell responses by codelivery of hIL-7 DNA was shown to be due to the enhancement of both the breadth and magnitude of immune responses against dominant and subdominant epitopes. CONCLUSION: Taken together, these findings suggest that the hIL-7-expressing plasmid serves as a promising vaccine adjuvant capable of eliciting enhanced vaccine-induced antibody and broad T cell responses.
Antibody Formation ; DNA ; Humans ; Interleukin-7 ; Macaca fascicularis ; Plasmids ; Primates ; Vaccination ; Vaccines, DNA

This study was performed to investigate the expression of two porcine endogenous retrovirus (PERV) elements, PERV gag and full-length conserved PERV, in blood cells collected periodically from organ-recipient monkeys that underwent pig to non-human primate xenotransplantation. The heart and kidney-respectively acquired from alpha-1,3-galactosyltransferase knockout (GT-KO) pigs that survived for24 and 25 days-were xenografted into cynomolgus monkeys. The two PERV elements expressed in the xenografted GT-KO pig organs were not present in the blood cells of the recipient monkeys. In the present study, we deduced that PERVs are not transmitted during GT-KO pig to monkey xenotransplantation.
Blood Cells ; Endogenous Retroviruses* ; Haplorhini* ; Heart ; Heterografts ; Macaca fascicularis ; Primates ; Swine ; Transplantation, Heterologous*

Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.
Bacteroidetes ; Diet ; Environment, Controlled ; Firmicutes ; Gastrointestinal Microbiome ; Haplorhini ; Macaca fascicularis ; Methods ; Microbiota ; Obesity ; Prevotella ; Primates ; Spirochaetales

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.
Animals ; Disease Models, Animal ; Female ; Gene Editing ; Humans ; Lamin Type A/metabolism* ; Macaca fascicularis ; Progeria/pathology*

Aging/metabolism* ; Animals ; Gene Expression Regulation ; Macaca fascicularis ; Retina/metabolism* ; Single-Cell Analysis

Many researchers are using viruses to deliver genes of interest into the brains of laboratory animals. However, certain target brain cells are not easily infected by viruses. Moreover, the differential tropism of different viruses in monkey brain is not well established. We investigated the cellular tropism of lentivirus and adeno-associated virus (AAV) toward neuron and glia in the brain of cynomolgus monkeys (Macaca fascularis). Lentivirus and AAV were injected into putamen of the monkey brain. One month after injection, monkeys were sacrificed, and then the presence of viral infection by expression of reporter fluorescence proteins was examined. Tissues were sectioned and stained with NeuN and GFAP antibodies for identifying neuronal cells or astrocytes, respectively, and viral reporter GFP-expressing cells were counted. We found that while lentivirus infected mostly astrocytes, AAV infected neurons at a higher rate than astrocytes. Moreover, astrocytes showed reactiveness when cells were infected by virus, likely due to virus-mediated neuroinflammation. The Sholl analysis was done to compare the hypertrophy of infected and uninfected astrocytes by virus. The lentivirus infected astrocytes showed negligible hypertrophy whereas AAV infected astrocytes showed significant changes in morphology, compared to uninfected astrocytes. In the brain of cynomolgus monkey, lentivirus shows tropism for astrocytes over neurons without much reactivity in astrocytes, whereas AAV shows tropism for neurons over glial cells with a significant reactivity in astrocytes. We conclude that AAV is best-suited for gene delivery to neurons, whereas lentivirus is the best choice for gene delivery to astrocytes in the brain of cynomolgus monkeys.
Animals, Laboratory ; Antibodies ; Astrocytes ; Brain* ; Dependovirus* ; Fluorescence ; Haplorhini ; Hypertrophy ; Lentivirus* ; Macaca fascicularis* ; Neuroglia ; Neurons ; Putamen ; Tropism*

OBJECTIVETo investigate the expression and the role of nitric oxide synthase (NOS) in the testis and epididymis of macaca fascicularis.

METHODSThe immunohistochemical ABC method was used to observe the localization of nitric oxide synthase in the testis and epididymis of the macaca fascicularis.

RESULTS(1) nNOS immunoreactivity was found in the spermatogenic cells of seminiferous tubules, the epithelia of epididymal efferent ducts, sperm and the endothelia of blood vessels; (2) iNOS was expressed in the epididymal efferent duct, the sperm inside the duct, and the myoid cells and endothelia of blood vessels; (3) eNOS immunoreactivity was detected in the interstitial cells of the testis, the epididymal efferent duct, the sperm inside the duct, and the myoid cells and endothelia of blood vessels.

CONCLUSIONNOS is extensively expressed in the testis and epididymis of the macaca fascicularis and it may play an important role in such processes as spermatogenesis, sperm maturation and testosterone secretion.

Animals ; Epididymis ; metabolism ; Immunohistochemistry ; Macaca fascicularis ; Male ; Nitric Oxide Synthase ; biosynthesis ; physiology ; Testis ; metabolism