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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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RPE cell size and relative abundance of binucleate RPE cells across the mouse and human retina.(A-C) Confocal images of a flatmount of a BALB/C mouse RPE, showing cells at retinal eccentricities of 0° (A), 40° (B), and 75° (C). Scale bar = 50 μm. (D) Graph of RPE cell cross-sectional area in relation to eccentricity in the mouse and human retinas. RPE cell size was significantly different between eccentricities in both mouse strains (P < 0.0001; Tukey’s test). (E) Graph of RPE cell density in relation to eccentricity in the mouse retinas, illustrating the proportion of binucleate cells, which was different between eccentricities in both mouse strains (P < 0.0001; Tukey’s test). Error bars in D and E indicate SEM. The human data are from Ts’o and Friedman [39].
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pone.0125631.g002: RPE cell size and relative abundance of binucleate RPE cells across the mouse and human retina.(A-C) Confocal images of a flatmount of a BALB/C mouse RPE, showing cells at retinal eccentricities of 0° (A), 40° (B), and 75° (C). Scale bar = 50 μm. (D) Graph of RPE cell cross-sectional area in relation to eccentricity in the mouse and human retinas. RPE cell size was significantly different between eccentricities in both mouse strains (P < 0.0001; Tukey’s test). (E) Graph of RPE cell density in relation to eccentricity in the mouse retinas, illustrating the proportion of binucleate cells, which was different between eccentricities in both mouse strains (P < 0.0001; Tukey’s test). Error bars in D and E indicate SEM. The human data are from Ts’o and Friedman [39].

Mentions: RPE wholemounts were prepared from 5 mice of each strain, and the central, mid-peripheral, and peripheral regions of the retina, corresponding approximately to visual angles of 0°, 40°, and 75°, respectively, were imaged (Fig 2A–2C) and measured. A clear difference was observed in the cross-sectional areas between the central and peripheral RPE cells. RPE cell area was 1.7 times larger in the central area than in the periphery of BALB/C mice, while the difference in C57BL/6J mice was somewhat smaller (Fig 2D). In contrast, human data show the opposite trend [39], where RPE cells have a significantly smaller cross-sectional area in the center of the retina than in the periphery (Fig 2D). The apical to basal depth of the RPE is fairly constant across both the mouse and human [39] retinas at ~5 and ~7 μm, respectively.


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)

RPE cell size and relative abundance of binucleate RPE cells across the mouse and human retina.(A-C) Confocal images of a flatmount of a BALB/C mouse RPE, showing cells at retinal eccentricities of 0° (A), 40° (B), and 75° (C). Scale bar = 50 μm. (D) Graph of RPE cell cross-sectional area in relation to eccentricity in the mouse and human retinas. RPE cell size was significantly different between eccentricities in both mouse strains (P < 0.0001; Tukey’s test). (E) Graph of RPE cell density in relation to eccentricity in the mouse retinas, illustrating the proportion of binucleate cells, which was different between eccentricities in both mouse strains (P < 0.0001; Tukey’s test). Error bars in D and E indicate SEM. The human data are from Ts’o and Friedman [39].
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4414478&req=5

pone.0125631.g002: RPE cell size and relative abundance of binucleate RPE cells across the mouse and human retina.(A-C) Confocal images of a flatmount of a BALB/C mouse RPE, showing cells at retinal eccentricities of 0° (A), 40° (B), and 75° (C). Scale bar = 50 μm. (D) Graph of RPE cell cross-sectional area in relation to eccentricity in the mouse and human retinas. RPE cell size was significantly different between eccentricities in both mouse strains (P < 0.0001; Tukey’s test). (E) Graph of RPE cell density in relation to eccentricity in the mouse retinas, illustrating the proportion of binucleate cells, which was different between eccentricities in both mouse strains (P < 0.0001; Tukey’s test). Error bars in D and E indicate SEM. The human data are from Ts’o and Friedman [39].
Mentions: RPE wholemounts were prepared from 5 mice of each strain, and the central, mid-peripheral, and peripheral regions of the retina, corresponding approximately to visual angles of 0°, 40°, and 75°, respectively, were imaged (Fig 2A–2C) and measured. A clear difference was observed in the cross-sectional areas between the central and peripheral RPE cells. RPE cell area was 1.7 times larger in the central area than in the periphery of BALB/C mice, while the difference in C57BL/6J mice was somewhat smaller (Fig 2D). In contrast, human data show the opposite trend [39], where RPE cells have a significantly smaller cross-sectional area in the center of the retina than in the periphery (Fig 2D). The apical to basal depth of the RPE is fairly constant across both the mouse and human [39] retinas at ~5 and ~7 μm, respectively.

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