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A comparison of some organizational characteristics of the mouse central retina and the human macula.

Volland S, Esteve-Rudd J, Hoo J, Yee C, Williams DS - PLoS ONE (2015)

Bottom Line: Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons.As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human.Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

View Article: PubMed Central - PubMed

Affiliation: Departments of Ophthalmology and Neurobiology, Stein Eye Institute, Molecular Biology Institute, Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.

ABSTRACT
Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

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Comparison of photoreceptor distribution in mouse and human retinas.(A) Graph showing the photoreceptor density per mm2 in mouse and human. Data from the visual angles of 0°, 20° and 40° were collected at distances of 0, 0.6 and 1.2 mm, respectively, from the center of the mouse retina, along the dorso-ventral axis (shown left to right; ON indicates the location of the optic nerve head, which is just ventral from the center). Data from the visual angles of 75° and 82° were collected from regions centered at distances of 250 and 50 μm from the ora serrata, which approximated to 2.3 and 2.5 mm from the center. Error bars indicate SEM. Inset shows a low power micrograph of a dorso-ventral section passing through the optic nerve head and the center of the retina (0°); scale bar = 0.3 mm. The human data are from temporal to nasal, as reported by Osterberg [38]. Visual angles of 20°, 40°, 60° and 70° correspond to distances of 6, 12, 18 and 20 mm from the fovea. (B-J) Representative light microscopic images of the regions sampled along the dorsoventral axis of the mouse retinas. Examples from both the BALB/C and C57BL/6J strains are included. (B) 82° dorsal, (C) 75° dorsal, (D) 40° dorsal, (E) 20° dorsal, (F) center, (G) 20° ventral, (H) 40° ventral, (I) 75° ventral, (J) 82° ventral. Scale bar = 25 μm.
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pone.0125631.g001: Comparison of photoreceptor distribution in mouse and human retinas.(A) Graph showing the photoreceptor density per mm2 in mouse and human. Data from the visual angles of 0°, 20° and 40° were collected at distances of 0, 0.6 and 1.2 mm, respectively, from the center of the mouse retina, along the dorso-ventral axis (shown left to right; ON indicates the location of the optic nerve head, which is just ventral from the center). Data from the visual angles of 75° and 82° were collected from regions centered at distances of 250 and 50 μm from the ora serrata, which approximated to 2.3 and 2.5 mm from the center. Error bars indicate SEM. Inset shows a low power micrograph of a dorso-ventral section passing through the optic nerve head and the center of the retina (0°); scale bar = 0.3 mm. The human data are from temporal to nasal, as reported by Osterberg [38]. Visual angles of 20°, 40°, 60° and 70° correspond to distances of 6, 12, 18 and 20 mm from the fovea. (B-J) Representative light microscopic images of the regions sampled along the dorsoventral axis of the mouse retinas. Examples from both the BALB/C and C57BL/6J strains are included. (B) 82° dorsal, (C) 75° dorsal, (D) 40° dorsal, (E) 20° dorsal, (F) center, (G) 20° ventral, (H) 40° ventral, (I) 75° ventral, (J) 82° ventral. Scale bar = 25 μm.

Mentions: Rod and cone photoreceptor cell nuclei were counted at locations along the dorso-ventral axis of mouse retinas. These locations were specified based on their distances from the center of the retina, and their corresponding angle from the optical axis. The center was identified by the peak in photoreceptor cell density, and was thus found at a distance of 400 μm dorsal from the center of the optic nerve head (Fig 1A). This point coincides with that reported to lie on the optical axis of the mouse eye [35]. Cone nuclei were distinguished from rod nuclei by their distal location and chromatin distribution [36, 37].


A comparison of some organizational characteristics of the mouse central retina and the human macula.

Volland S, Esteve-Rudd J, Hoo J, Yee C, Williams DS - PLoS ONE (2015)

Comparison of photoreceptor distribution in mouse and human retinas.(A) Graph showing the photoreceptor density per mm2 in mouse and human. Data from the visual angles of 0°, 20° and 40° were collected at distances of 0, 0.6 and 1.2 mm, respectively, from the center of the mouse retina, along the dorso-ventral axis (shown left to right; ON indicates the location of the optic nerve head, which is just ventral from the center). Data from the visual angles of 75° and 82° were collected from regions centered at distances of 250 and 50 μm from the ora serrata, which approximated to 2.3 and 2.5 mm from the center. Error bars indicate SEM. Inset shows a low power micrograph of a dorso-ventral section passing through the optic nerve head and the center of the retina (0°); scale bar = 0.3 mm. The human data are from temporal to nasal, as reported by Osterberg [38]. Visual angles of 20°, 40°, 60° and 70° correspond to distances of 6, 12, 18 and 20 mm from the fovea. (B-J) Representative light microscopic images of the regions sampled along the dorsoventral axis of the mouse retinas. Examples from both the BALB/C and C57BL/6J strains are included. (B) 82° dorsal, (C) 75° dorsal, (D) 40° dorsal, (E) 20° dorsal, (F) center, (G) 20° ventral, (H) 40° ventral, (I) 75° ventral, (J) 82° ventral. Scale bar = 25 μm.
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pone.0125631.g001: Comparison of photoreceptor distribution in mouse and human retinas.(A) Graph showing the photoreceptor density per mm2 in mouse and human. Data from the visual angles of 0°, 20° and 40° were collected at distances of 0, 0.6 and 1.2 mm, respectively, from the center of the mouse retina, along the dorso-ventral axis (shown left to right; ON indicates the location of the optic nerve head, which is just ventral from the center). Data from the visual angles of 75° and 82° were collected from regions centered at distances of 250 and 50 μm from the ora serrata, which approximated to 2.3 and 2.5 mm from the center. Error bars indicate SEM. Inset shows a low power micrograph of a dorso-ventral section passing through the optic nerve head and the center of the retina (0°); scale bar = 0.3 mm. The human data are from temporal to nasal, as reported by Osterberg [38]. Visual angles of 20°, 40°, 60° and 70° correspond to distances of 6, 12, 18 and 20 mm from the fovea. (B-J) Representative light microscopic images of the regions sampled along the dorsoventral axis of the mouse retinas. Examples from both the BALB/C and C57BL/6J strains are included. (B) 82° dorsal, (C) 75° dorsal, (D) 40° dorsal, (E) 20° dorsal, (F) center, (G) 20° ventral, (H) 40° ventral, (I) 75° ventral, (J) 82° ventral. Scale bar = 25 μm.
Mentions: Rod and cone photoreceptor cell nuclei were counted at locations along the dorso-ventral axis of mouse retinas. These locations were specified based on their distances from the center of the retina, and their corresponding angle from the optical axis. The center was identified by the peak in photoreceptor cell density, and was thus found at a distance of 400 μm dorsal from the center of the optic nerve head (Fig 1A). This point coincides with that reported to lie on the optical axis of the mouse eye [35]. Cone nuclei were distinguished from rod nuclei by their distal location and chromatin distribution [36, 37].

Bottom Line: Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons.As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human.Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

View Article: PubMed Central - PubMed

Affiliation: Departments of Ophthalmology and Neurobiology, Stein Eye Institute, Molecular Biology Institute, Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America.

ABSTRACT
Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

Show MeSH
Related in: MedlinePlus