Measuring Cone Density in a Japanese Macaque (Macaca fuscata) Model of Age-Related Macular Degeneration with Commercially Available Adaptive Optics

Pennesi, Mark E.; Garg, Anupam; Feng, Shu; Michaels, Keith V.; Smith, Travis B.; Fay, Jonathan; Weiss, Alison R.; Renner, Lauren; Hurst, Sawan; McGill, Trevor J.; Cornea, Anda; Rittenhouse, Kay D.; Sperling, Marvin; Fruebis, Joachim; Neuringer, Martha

doi:10.1007/978-1-4614-3209-8_39

Cited by 8 publications

(6 citation statements)

References 11 publications

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“…Thus, developing nonhuman primate models with more advanced stages of AMD may require long-term dietary and environmental modifications that better represent human behavior. Interestingly, Japanese macaques (Macaca fuscata) have an early-onset form of drusen with a dominant mode of inheritance 42 . Cynomologus macaques (Macaca fascicularis) also develop drusen in an age-dependent manner with a potential link to hematologic markers 43 .…”

Section: Discussionmentioning

confidence: 99%

In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques

Yiu

Tieu

Munevar

et al. 2017

Sci Rep

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Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes – 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruch’s membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates.

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Section: Discussionmentioning

confidence: 99%

In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques

Yiu

Tieu

Munevar

et al. 2017

Sci Rep

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“…Early studies reported a high prevalence of drusenoid pathology (30%-74%) in free-ranging rhesus macaques (Macaca mulatta) from Cayo Santiago in Puerto Rico, [8][9][10][11] whereas other colonies within the continental United States have shown variable prevalences (5%-47%), likely due to differences in environmental conditions, diet, and genetic background. [12][13][14][15] Cynomolgus and Japanese macaques (Macaca fascicularis and Macaca fuscata) also exhibit an early onset form of the disease with a dominant mode of inheritance, [16][17][18][19][20][21] but the precise genetic basis remains unclear. 20 Rhesus monkeys with drusenoid lesions share genetic polymorphisms in the age-related maculopathy susceptibility 2 (ARMS2) locus with human patients with AMD [22][23][24] and demonstrate similar protein components within the drusen lesions, 19 suggesting common mechanisms between drusen formation in humans and nonhuman primates.…”

mentioning

confidence: 99%

Long-term Evolution and Remodeling of Soft Drusen in Rhesus Macaques

Yiu

Chung

Mollhoff

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To characterize the evolution and structure of soft drusen in aged rhesus macaques using in vivo multimodal retinal imaging and ex vivo histologic and ultrastructural analyses as a nonhuman primate model of early age-related macular degeneration (AMD). METHODS.Multimodal imaging including fundus photography, spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were used to characterize and track individual drusen lesions in 20 aged rhesus macaques (mean age 23.3 ± 2.7 years) with drusenoid lesions over 2 years, followed by semithin histologic analysis and transmission electron microscopy (TEM). RESULTS.Although most drusen gradually increased in size, a portion spontaneously regressed or collapsed over 2 years. Histologic analyses showed that soft drusen exhibit hypertrophy and dysmorphia of overlying retinal pigment epithelium (RPE), as seen in early and intermediate AMD, but do not exhibit RPE atrophy, RPE migration, or photoreceptor degeneration characteristic of advanced AMD. Ultrastructure of soft drusen showed abundant lipid particles within Bruch's membrane and AMD-related basal linear deposits (BlinD) resembling those in human drusen. CONCLUSIONS.The dynamic remodeling, histologic findings, and ultrastructural features of soft drusen in aged rhesus macaques support nonhuman primates as an animal model of early AMD and reveal important insights into drusen biogenesis and AMD development.

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“…The concept of a visual fovea is well known. The density of cones in the retina of the eye peaks as we approach the center of the back of the eye [5,33,42]. This foveation gives us high acuity in our central vision.…”

Section: Biological Inspiration Foveation In Visionmentioning

confidence: 99%

A customizable artificial auditory fovea

Casebeer

Snider

2018

The Journal of the Acoustical Society of America

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Neuroscience shows that auditory neurons extract a variety of specific signal parameters such as frequency, amplitude modulation, frequency modulation, and onsets. Furthermore, biology gives us examples of auditory foveae in bats and owls where there is overrepresentation of behaviorally relevant signal parameters. This shows that biology finds nuances of these parameters to be more important than compact coding considerations such as orthonormal basis functions. In contrast to typical spectrogram approaches where a specific time window is chosen and where the Fast Fourier Transform provides non-overlapping orthogonal rectangular tilings, we start with the smallest tiling possible. The uncertainty principle gives us this tiling as the Gaussian modulated sinusoid. We can rotate this tiling in the time-frequency plane, which gives us a chirplet. We then construct many chirplets (a chirplet set) centered at the same time-frequency point. We then find the chirplet that best matches the signal at this point. Our ability to sample at arbitrary locations in the time-frequency plane with different chirplet sets gives us the ability to create customizable artificial auditory foveae. We use this chirplet front-end for a classification task of identifying Marmoset vocalizations and comparisons to typical spectrogram methods for audio classification are made.

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Measuring Cone Density in a Japanese Macaque (Macaca fuscata) Model of Age-Related Macular Degeneration with Commercially Available Adaptive Optics

Cited by 8 publications

References 11 publications

In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques

In Vivo Multimodal Imaging of Drusenoid Lesions in Rhesus Macaques

Long-term Evolution and Remodeling of Soft Drusen in Rhesus Macaques

A customizable artificial auditory fovea

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