Drusenoid maculopathy in rhesus monkeys (Macaca mulatta): Effects of age and gender

Peter Gouras, Lena Ivert, Noelle Landauer, Julie A. Mattison, Donald K. Ingram, Martha Neuringer

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    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 six 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.

    Original languageEnglish (US)
    Pages (from-to)1395-1402
    Number of pages8
    JournalGraefe's Archive for Clinical and Experimental Ophthalmology
    Volume246
    Issue number10
    DOIs
    StatePublished - 2008

    Fingerprint

    Macaca mulatta
    Haplorhini
    Caloric Restriction
    Diet
    Retina
    Geographic Atrophy
    Ophthalmoscopy
    Fluorescein Angiography
    Photography
    Macular Degeneration
    Young Adult
    Histology
    Observation

    Keywords

    • Age-related macular degeneration
    • Caloric restriction
    • Diet
    • Drusen
    • Macula
    • Monkey

    ASJC Scopus subject areas

    • Ophthalmology

    Cite this

    Drusenoid maculopathy in rhesus monkeys (Macaca mulatta) : Effects of age and gender. / Gouras, Peter; Ivert, Lena; Landauer, Noelle; Mattison, Julie A.; Ingram, Donald K.; Neuringer, Martha.

    In: Graefe's Archive for Clinical and Experimental Ophthalmology, Vol. 246, No. 10, 2008, p. 1395-1402.

    Research output: Contribution to journalArticle

    Gouras, Peter ; Ivert, Lena ; Landauer, Noelle ; Mattison, Julie A. ; Ingram, Donald K. ; Neuringer, Martha. / Drusenoid maculopathy in rhesus monkeys (Macaca mulatta) : Effects of age and gender. In: Graefe's Archive for Clinical and Experimental Ophthalmology. 2008 ; Vol. 246, No. 10. pp. 1395-1402.
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    abstract = "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 six 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.",
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    AU - Ivert, Lena

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    AU - Mattison, Julie A.

    AU - Ingram, Donald K.

    AU - Neuringer, Martha

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    N2 - 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 six 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.

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    KW - Drusen

    KW - Macula

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