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1.  Chapter 39 Measuring Cone Density in a Japanese Macaque (Macaca fuscata) Model of Age-Related Macular Degeneration with Commercially Available Adaptive Optics 
The aim of this study was to assess the feasibility of using a commercially available high-resolution adaptive optics (AO) camera to image the cone mosaic in Japanese macaques (Macaca fuscata) with dominantly inherited drusen. The macaques examined develop drusen closely resembling those seen in humans with age-related macular degeneration (AMD). For each animal, we acquired and processed images from the AO camera, montaged the results into a composite image, applied custom cone-counting software to detect individual cone photoreceptors, and created a cone density map of the macular region. We conclude that flood-illuminated AO provides a promising method of visualizing the cone mosaic in nonhuman primates. Future studies will quantify the longitudinal change in the cone mosaic and its relationship to the severity of drusen in these animals.
doi:10.1007/978-1-4614-3209-8_39
PMCID: PMC4332712  PMID: 24664712
Cone density imaging; adaptive optics; flood-illuminated adaptive optics; AMD
2.  Safety and Effects of the Vector for the Leber Hereditary Optic Neuropathy Gene Therapy Clinical Trial 
JAMA ophthalmology  2014;132(4):409-420.
IMPORTANCE
We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene.
OBJECTIVE
To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial.
DESIGN AND SETTING
In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON.
EXPOSURE
Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene.
MAIN OUTCOMES AND MEASURES
Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4.
RESULTS
We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3 months had no serious adverse reactions.
CONCLUSIONS AND RELEVANCE
Expression of our allotopic ND4 vector in the ex vivo human eye, safety of the test article, rescue of the LHON mouse model, and the severe irreversible loss of visual function in LHON support clinical testing with mutated G11778A mitochondrial DNA in our patients.
doi:10.1001/jamaophthalmol.2013.7630
PMCID: PMC4266107  PMID: 24457989
3.  Dietary Omega-3 Fatty Acids Modulate Large-Scale Systems Organization in the Rhesus Macaque Brain 
The Journal of Neuroscience  2014;34(6):2065-2074.
Omega-3 fatty acids are essential for healthy brain and retinal development and have been implicated in a variety of neurodevelopmental disorders. This study used resting-state functional connectivity MRI to define the large-scale organization of the rhesus macaque brain and changes associated with differences in lifetime ω-3 fatty acid intake. Monkeys fed docosahexaenoic acid, the long-chain ω-3 fatty acid abundant in neural membranes, had cortical modular organization resembling the healthy human brain. In contrast, those with low levels of dietary ω-3 fatty acids had decreased functional connectivity within the early visual pathway and throughout higher-order associational cortex and showed impairment of distributed cortical networks. Our findings illustrate the similarity in modular cortical organization between the healthy human and macaque brain and support the notion that ω-3 fatty acids play a crucial role in developing and/or maintaining distributed, large-scale brain systems, including those essential for normal cognitive function.
doi:10.1523/JNEUROSCI.3038-13.2014
PMCID: PMC3913863  PMID: 24501348
brain organization; DHA; functional connectivity; macaque development; omega-3 fatty acids; visual pathway
4.  Changes in spontaneous activity assessed by accelerometry correlate with extent of cerebral ischemia-reperfusion injury in the nonhuman primate 
Translational stroke research  2012;3(4):442-451.
The use of accelerometry to monitor activity in human stroke patients has revealed strong correlations between objective activity measurements and subjective neurological findings. The goal of our study was to assess the applicability of accelerometry-based measurements in experimental animals undergoing surgically-induced cerebral ischemia. Using a nonhuman primate cortical stroke model, we demonstrate for the first time that monitoring locomotor activity prior to and following cerebrovascular ischemic injury using an accelerometer is feasible in adult male rhesus macaques and that the measured activity outcomes significantly correlate with severity of brain injury. The use of accelerometry as an unobtrusive, objective preclinical efficacy determinant could complement standard practices involving subjective neurological scoring and magnetic resonance imaging in nonhuman primates. Similar activity monitoring devices to those employed in this study are currently in use in human clinical studies, underscoring the feasibility of this approach for assessing the clinical potential of novel treatments for cerebral ischemia.
doi:10.1007/s12975-012-0191-8
PMCID: PMC3619447  PMID: 23580904
accelerometer; actigraphy; ischemia; nonhuman primate; rhesus macaque; stroke
5.  Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates 
Nutritional neuroscience  2012;16(1):10.1179/1476830512Y.0000000024.
Objectives
Xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain tissue. The objective of the study was to evaluate the relationship between retinal and brain levels of these xanthophylls in non-human primates.
Methods
Study animals included rhesus monkeys reared on diets devoid of xanthophylls that were subsequently fed pure lutein or pure zeaxanthin (both at 3.9 μmol/kg*d, n=6/group) and normal rhesus monkeys fed a stock diet (0.26 μmol/kg*d lutein and 0.24 μmol/kg*d zeaxanthin, n=5). Retina (4 mm macular punch, 4-8 mm annulus and periphery) and brain tissue (cerebellum, frontal cortex, occipital cortex and pons) from the same animals were analyzed by reverse phase HPLC.
Results
Lutein in the macula and annulus were significantly related to lutein levels in the cerebellum, occipital cortex and pons, both in bivariate analysis and after adjusting for age, sex and n–3 fatty acid status. In the frontal cortex the relationship was marginally significant. Macular zeaxanthin was significantly related to zeaxanthin in the cerebellum and frontal cortex, while the relationship was marginally significant in the occipital cortex and pons in a bivariate model.
Discussion
An integrated measure of total macular pigment optical density, which can be measured noninvasively, has the potential to be used as a biomarker to assess brain lutein and zeaxanthin status.
doi:10.1179/1476830512Y.0000000024
PMCID: PMC3824968  PMID: 22780947
brain; cognition; lutein; macula; zeaxanthin
6.  Animal models of age related macular degeneration 
Molecular aspects of medicine  2012;33(4):487-509.
Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.
doi:10.1016/j.mam.2012.06.003
PMCID: PMC3770531  PMID: 22705444
7.  Accelerated immune senescence and reduced response to vaccination in ovariectomized female rhesus macaques 
Age  2010;33(3):275-289.
Aging is associated with a general dysregulation in immune function, commonly referred to as “immune senescence”. Several studies have shown that female sex steroids can modulate the immune response. However, the impact of menopause-associated loss of estrogen and progestins on immune senescence remains poorly understood. To help answer this question, we examined the effect of ovariectomy on T-cell homeostasis and function in adult and aged female rhesus macaques. Our data show that in adult female rhesus macaques, ovariectomy increased the frequency of naïve CD4 T cells. In contrast, ovariectomized (ovx) aged female rhesus macaques had increased frequency of terminally differentiated CD4 effector memory T cells and inflammatory cytokine-secreting memory T cells. Moreover, ovariectomy reduced the immune response (T-cell cytokine and IgG production) following vaccination with modified vaccinia ankara in both adult and aged female rhesus macaques compared to ovary-intact age-matched controls. Interestingly, hormone therapy (estradiol alone or in conjunction with progesterone) partially improved the T-cell response to vaccination in aged ovariectomized female rhesus macaques. These data suggest that the loss of ovarian steroids, notably estradiol and progesterone, may contribute to reduced immune function in post-menopausal women and that hormone therapy may improve immune response to vaccination in this growing segment of the population.
doi:10.1007/s11357-010-9178-0
PMCID: PMC3168610  PMID: 20814751
Aging; Immune senescence; Ovariectomy; T cells; Vaccine; Estrogen; Progestin
8.  Metabolism of Lutein and Zeaxanthin in Rhesus Monkeys: Identification of (3R,6′R)- and (3R,6′S)-3′-Dehydro-lutein as Common Metabolites and Comparison to Humans 
Lutein and zeaxanthin are xanthophylls that can be found highly concentrated in the macula of the retina. They are thought to protect the macula through their role as blue-light filters and because of their antioxidant and singlet oxygen quenching properties. Examination of metabolites unique to lutein and zeaxanthin such as 3′-dehydro-lutein, and of their stereochemistry may provide insight to the mechanism by which they are formed and by which they exert protection. To evaluate the formation of such metabolites, eleven monkeys were raised on a xanthophyll-free diet, and supplemented with pure lutein or pure zeaxanthin (2.2 mg/kg body weight/d). The period of supplementation ranged between 12 to 92 weeks. At study start and throughout the study, serum samples were taken and analyzed for xanthophylls using different HPLC systems. Xanthophyll metabolites were identified using UV/VIS and HR-MS detection. Lutein and zeaxanthin metabolites were found in detectable amounts with 3′-dehydro-lutein being a common metabolite of both. Using chiral-phase HPLC, two diastereomers, (3R,6′R)-3′-dehydro-lutein and (3R,6′S)-3′-dehydro-lutein, were identified and shown to be present in nearly equimolar amounts. A pathway for their formation from either lutein or zeaxanthin is proposed. These finding were comparable to results obtained with human plasma.
doi:10.1016/j.cbpb.2008.05.014
PMCID: PMC3419355  PMID: 18582588
Chiral analysis; 3′-Dehydro-lutein; Human plasma; Lutein; Rhesus monkey serum; Serum metabolites; Zeaxanthin
9.  Nutritional Manipulation of Primate Retinas, V: Effects of Lutein, Zeaxanthin, and n–3 Fatty Acids on Retinal Sensitivity to Blue-Light–Induced Damage 
Acute foveal blue-light–induced damage was greater in monkeys fed xanthophyll-free diets and lacking macular pigment than in normal monkeys, but decreased to normal after supplementation with lutein or zeaxanthin. Monkeys that were also deficient in n-3 fatty acids had greater damage in the parafovea. These findings support both nutrients' protective role in macular disease.
Purpose.
Blue-light photooxidative damage has been implicated in the etiology of age-related macular degeneration (AMD). The macular pigment xanthophylls lutein (L) and zeaxanthin (Z) and n–3 fatty acids may reduce this damage and lower the risk of AMD. This study investigated the effects of the lifelong absence of xanthophylls followed by L or Z supplementation, combined with the effects of n–3 fatty acid deficiency, on acute blue-light photochemical damage.
Methods.
Subjects included eight rhesus monkeys with no lifelong intake of xanthophylls and no detectable macular pigment. Of these, four had low n–3 fatty acid intake and four had adequate intakes. Control subjects had typical L, Z, and n–3 fatty acid intake. Retinas received 150-μm-diameter exposures of low-power 476-nm laser light at 0.5 mm (∼2°) eccentricity, which is adjacent to the macular pigment peak, and parafoveally at 1.5 mm (∼6°). Exposures of xanthophyll-free animals were repeated after supplementation with pure L or Z for 22 to 28 weeks. Ophthalmoscopically visible lesion areas were plotted as a function of exposure energy, with greater slopes of the regression lines indicating greater sensitivity to damage.
Results.
In control animals, the fovea was less sensitive to blue-light–induced damage than the parafovea. Foveal protection was absent in xanthophyll-free animals but was evident after supplementation. In the parafovea, animals low in n–3 fatty acids showed greater sensitivity to damage than animals with adequate levels.
Conclusions.
After long-term xanthophyll deficiency, L or Z supplementation protected the fovea from blue light–induced damage, whereas adequate n–3 fatty acid levels reduced the damage in the parafovea.
doi:10.1167/iovs.10-5898
PMCID: PMC3175953  PMID: 21245404
10.  Age-Related Decline in Rod Phototransduction Sensitivity in Rhesus Monkeys Fed an n-3 Fatty Acid Deficient Diet 
Purpose
Docosahexaenoic acid (DHA), an n-3 fatty acid is the major polyunsaturate in rod outer segments. The effect of long term n-3 fatty acid deficiency on rod and cone phototransduction was investigated in the rhesus monkey.
Methods
From birth to ≅ 9 years rhesus monkeys were fed an n-3 deficient diet (n=9) known to reduce retinal DHA by 80%. Monkeys in the control group (n=12) received either 8% α-linolenic acid (ALA) or 0.6% DHA both of which support normal retinal DHA levels. None of the diets contained carotenoids. Photoactivation kinetics were assessed from the rate of increase, and a P3 model fit of the ERG a-wave. Maximal cone amplitude and sensitivity were measured from the cone a-wave at 4 ms. The rod photoresponse and rod recovery were derived using a paired flash method.
Results
Rod sensitivity was reduced by 40% in the n-3 deficient monkeys at 9 but not 4.5 years. The onset of the rising phase of the photoresponse was significantly delayed (p<0.004) at 9 years. Rod recovery was delayed by 20% in n-3 deficient monkeys at both ages, but only for bright saturating flashes. Cone phototransduction was not altered by n-3 deficiency
Conclusions
Long-term dietary n-3 deficiency in the rhesus monkey was associated with two changes in retinal function. First, there was a delay in rod recovery that has remained relatively constant throughout life. Second, there was an age dependent loss in rod phototransduction sensitivity; the lack of dietary carotenoids may have contributed to this decline.
doi:10.1167/iovs.09-3640
PMCID: PMC2824542  PMID: 19369246
11.  Subretinal Transplantation of Forebrain Progenitor Cells in Non-human Primates: Survival and Intact Retinal Function 
Purpose
Cell-based therapy rescues retinal structure and function in rodent models of retinal disease, but translation to clinic will require more information about consequences of transplantation in an eye closely resembling the human eye. Therefore we explored donor cell behavior using human cortical neural progenitor cells (hNPCctx) introduced into the subretinal space of normal rhesus macaques.
Methods
hNPCctx transduced with Green Fluorescent Protein (hNPCctx-GFP) were delivered bilaterally into the subretinal space of six normal adult rhesus macaques under conditions paralleling those of the human operating room. Outcome measures included clinical parameters of surgical success, multifocal electroretinogram (mfERG) and histopathological analyses performed between 3 and 39 days post-engraftment. To test the effects of GFP transduction on cell bioactivity, hNPCctx –GFP from the same batch were also injected into RCS rats and compared with non-labeled hNPCctx.
Results
Studies using RCS rats indicated that GFP transduction did not alter the ability of the cells to rescue vision. After cells were introduced into the monkey subretinal space by a pars plana transvitreal approach, the resulting detachment was rapidly resolved and retinal function showed little or no disturbance in mfERG recordings. Retinal structure was unaffected and no signs of inflammation or rejection were seen. Donor cells survived as a single layer in the subretinal space and no cells migrated into the inner retina.
Conclusions
Human neural progenitor cells can be introduced into a primate eye without complication, using an approach that would be suitable for extrapolation to human patients.
doi:10.1167/iovs.08-2908
PMCID: PMC2826708  PMID: 19234356
12.  Rhesus monkeys and humans share common susceptibility genes for age-related macular disease 
Human Molecular Genetics  2008;17(17):2673-2680.
Age-related macular degeneration (AMD), a complex multigenic disorder and the most common cause of vision loss in the elderly, is associated with polymorphisms in the LOC387715/ARMS2 and HTRA1 genes on 10q26. Like humans, macaque monkeys possess a macula and develop age-related macular pathologies including drusen, the phenotypic hallmark of AMD. We genotyped a cohort of 137 unrelated rhesus macaques with and without macular drusen. As in humans, one variant within LOC387715/ARMS2 and one in HTRA1 were significantly associated with affected status. HTRA1 and the predicted LOC387715/ARMS2 gene were both transcribed in rhesus and human retina and retinal pigment epithelium. Among several primate species, orthologous exons for the human LOC387715/ARMS2 gene were present only in Old World monkeys and apes. In functional analyses, the disease-associated HTRA1 polymorphism resulted in a 2-fold increase in gene expression, supporting a role in pathogenesis. These results demonstrate that two genes associated with AMD in humans are also associated with macular disease in rhesus macaques and that one of these genes is specific to higher primates. This is the first evidence that humans and macaques share the same genetic susceptibility factors for a common complex disease.
doi:10.1093/hmg/ddn167
PMCID: PMC2733804  PMID: 18535016
13.  Serum lutein concentrations in healthy term infants fed human milk or infant formula with lutein 
European Journal of Nutrition  2009;49(1):45-51.
Background
Lutein is a carotenoid that may play a role in eye health. Human milk typically contains higher concentrations of lutein than infant formula. Preliminary data suggest there are differences in serum lutein concentrations between breastfed and formula-fed infants.
Aim of the study
To measure the serum lutein concentrations among infants fed human milk or formulas with and without added lutein.
Methods
A prospective, double-masked trial was conducted in healthy term formula-fed infants (n = 26) randomized between 9 and 16 days of age to study formulas containing 20 (unfortified), 45, 120, and 225 mcg/l of lutein. A breastfed reference group was studied (n = 14) and milk samples were collected from their mothers. Primary outcome was serum lutein concentration at week 12.
Results
Geometric mean lutein concentration of human milk was 21.1 mcg/l (95% CI 14.9–30.0). At week 12, the human milk group had a sixfold higher geometric mean serum lutein (69.3 mcg/l; 95% CI 40.3–119) than the unfortified formula group (11.3 mcg/l; 95% CI 8.1–15.8). Mean serum lutein increased from baseline in each formula group except the unfortified group. Linear regression equation indicated breastfed infants had a greater increase in serum lutein (slope 3.7; P < 0.001) per unit increase in milk lutein than formula-fed infants (slope 0.9; P < 0.001).
Conclusions
Breastfed infants have higher mean serum lutein concentrations than infants who consume formula unfortified with lutein. These data suggest approximately 4 times more lutein is needed in infant formula than in human milk to achieve similar serum lutein concentrations among breastfed and formula fed infants.
doi:10.1007/s00394-009-0047-5
PMCID: PMC2801838  PMID: 19672550
Lutein; Human milk; Infant formula; Serum; Bioavailability
14.  Effect of optimal dietary therapy upon visual function in children with long-chain 3-hydroxyacyl CoA dehydrogenase and trifunctional protein deficiency 
Molecular genetics and metabolism  2005;86(1-2):124-133.
The objective of this prospective cohort study was to determine if dietary therapy including docosahexaenoic acid (DHA; C22:6ω-3) supplementation prevents the progression of the severe chorioretinopathy that develops in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency. Physical, biochemical, and ophthalmological evaluations, including electroretinogram (ERG) and visual acuity by evoked potential (VEP), were performed at baseline and annually following the initiation of 65–130 mg/day DHA supplementation and continued treatment with a low-fat diet. Fourteen children with LCHAD or TFP deficiency, 1–12 years of age at enrollment, were followed for 2–5 years. Three subjects with TFP β-subunit mutations had normal appearance of the posterior pole of the ocular fundi at enrollment and no changes over the course of the study. Eleven subjects who were homozygote and heterozygote for the common mutation, c.1528G > C, had no change to severe progression of atrophy of the choroid and retina with time. Of these, four subjects had marked to severe chorioretinopathy associated with high levels of plasma hydroxyacylcarnitines and decreased color, night and/or central vision during the study. The plasma level of long-chain 3-hydroxyacylcarnitines, metabolites that accumulate as a result of LCHAD and TFP deficiency, was found to be negatively correlated with maximum ERG amplitude (Rmax) (p=0.0038, R2=0.62). In addition, subjects with sustained low plasma long-chain 3-hydroxyacylcarnitines maintained higher ERG amplitudes with time compared to subjects with chronically high 3-hydroxyacylcarnitines. Visual acuity, as determined with the VEP, appeared to increase with time on DHA supplementation (p=0.051) and there was a trend for a positive correlation with plasma DHA concentrations (p=0.075, R2=0.31). Thus, optimal dietary therapy as indicated by low plasma 3-hydroxyacylcarnitine and high plasma DHA concentrations was associated with retention of retinal function and visual acuity in children with LCHAD or TFP deficiency.
doi:10.1016/j.ymgme.2005.06.001
PMCID: PMC2694051  PMID: 16040264
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency; Trifunctional protein deficiency; Hydroxyacylcarnitines; Docosahexaenoic acid; Chorioretinopathy
15.  Drusenoid maculopathy in rhesus monkeys: Autofluorescence, lipofuscin and drusen pathogenesis 
Purpose
To examine patterns of retinal pigment epithelial autofluorescence and lipofuscin accumulation in relation to drusen and to explore the pathogenesis of drusen in rhesus monkeys.
Methods
The macular areas of six rhesus monkeys, euthanized at 19 to 28 years of age, were studied by bright field and fluorescence light microscopy and transmission electron microscopy.
Results
There was strong autofluorescence in the retinal epithelium which tended to diminish over drusen. Electron microscopy revealed that all retinal epithelial cells had large concentrations of lipofuscin bodies. The epithelial cells overlying drusen, however, tended to have less lipofuscin than epithelial cells not associated with drusen. Electron microscopy revealed that the epithelial cells overlying drusen were losing segments of cytoplasm containing lipofuscin bodies. Macrophage-like cells were consistently present in Bruch’s membrane microns away from this lipofuscin-containing cytoplasmic material.
Conclusions
Retinal epithelial cells overlying drusen have less lipofuscin than neighboring epithelial cells. The loss of lipofuscin seems due to a loss of cytoplasm containing lipofuscin that contributes to drusen formation. Macrophages in Bruch’s membrane may be responsible for removing this lipofuscin debris. The results support in vivo studies showing reduced autofluorescence over drusen and support the “budding” of epithelial cytoplasm as a source of drusen material.
doi:10.1007/s00417-008-0911-7
PMCID: PMC2562037  PMID: 18696097
macula; age-related macular degeneration; drusen; lipofuscin; autofluorescence; monkey
16.  Drusenoid maculopathy in rhesus monkeys (Macaca mulatta): Effects of age and gender 
Purpose
To compare drusenoid maculopathy in monkeys with human age-related macular degeneration and evaluate the influence of age, gender and caloric restriction.
Methods
Examination by indirect ophthalmoscopy, slit lamp biomicroscopy and fundus photography, including in some cases fluorescein angiography, was performed on 61 male and 60 female rhesus macaques of ages 10-39 years. Fifty-four of the monkeys were maintained on a calorically restricted diet (approximately 30% lower than control levels) and 67 on an approximately ad libitum diet for 2-19 years, with all other environmental factors held constant. Maculopathies were graded on a 5-point scale and the effects of age, sex, and diet on prevalence and severity were examined. The retinas of 6 monkeys with macular drusen, 19-28 years old, were examined histologically.
Results
Rhesus monkeys showed a high prevalence (61 %) of drusenoid maculopathy. The prevalence and severity of the maculopathy increased with age (p =0.012). Fully half of all monkeys aged 10-12 years had some detectable degree of drusen. This high prevalence in young adulthood indicates that drusen develop much earlier in rhesus monkeys than in humans, who develop early maculopathy most rapidly at 50-60 years of age, even when correcting for the 3-fold difference in lifespan. No neovascularization or geographic atrophy was found. Females had a higher prevalence and severity than males (p=0.019). Calorically restricted monkeys had a slightly lower prevalence and severity at 10-12 years than controls, but the difference was not statistically significant. This is an on-going project and differences between the caloric restricted and ad-lib groups may emerge as the animals age. Some monkeys developed severe maculopathy in their 20s with others unaffected in their 30s. The histology of drusen resembled those in human retina.
Conclusion
Drusenoid maculopathy is common in rhesus monkeys even in young adult life. Half of the rhesus monkeys examined have drusen at a much younger age than in humans. Severity of maculopathy was greater in female monkeys, a gender difference not consistently found in humans. No differences were detected due to caloric restriction, but a definitive test of this intervention will require a larger sample, longer period of observation, and/or an earlier institution of caloric restriction. Genetic factors are implied because with similar environments, some monkeys are affected at an early age, while older ones are not.
doi:10.1007/s00417-008-0910-8
PMCID: PMC2562342  PMID: 18709381
macula; age-related macular degeneration; drusen; caloric restriction; diet; monkey

Results 1-16 (16)