Aging and degeneration of the human macula. 1. Outer nuclear layer and photoreceptors.

Abstract

SUMMARY In a light microscopic study of the macula of 104 human eyes obtained at necropsy of patients aged 3 to 96 we found: (1) Displacement of nuclei from the outer nuclear layer into the outer plexiform layer occurred in small numbers early in life and markedly increased after age 30.(2) Displacement of nuclei from the outer nuclear layer to the layer of rods and cones was rare in early life but increased considerably after age 40. (3) Displacement of nuclei is probably secondary to shrinkage of their attached fibres and is associated with aging. (4) Displaced nuclei apparently undergo changes in size, shape, and chromatin content and may go on to necrosis. (5) Twenty-four of the 104 eyes studied had an obvious reduction in the numbers of nuclei in the outer nuclear layer and their photoreceptors in the macular zone. All were in eyes from patients over age 40. No concomitant defect was found in the subjacent pigment epithelium, Bruch's membrane, or the choriocapillaris. The loss of nuclei of the outer nuclear layer appears to be a primary retinal disorder associated with aging.We found in the macula a loss of nuclei from the outer nuclear layer (ONL) which increased with age. This loss apparently starts with displacement or migration of nuclei from the ONL into the outer plexiform layer (OPL) and into the layer of rods and cones. This observation has received little or no attention and we could not find any previous systematic study in the literature. Material and methodsOne-hundred-and-four eyes obtained at necropsy from patients aged 3 to 96 were selected for study because sections included the macular region. Fiftytwo of these eyes had sections through the fovea. Only eyes without significant inflammatory or degenerative disease or trauma were studied. Eyes with disciform degeneration or with pigment migration into the retina were excluded. The eyes were opened in the horizontal meridian so that sections included the disc and macula. They were prepared with celloidin embedding cut 14 rum thick and stained with haematoxylin and eosin. The macula includes the fovea and parafoveal zone. Its outer boundary was the point where the ganglion cell layer was less than 2 cells thick. Sections were examined by light microscopy and the total numbers of displaced nuclei in the macula counted for each section. At least 3 slides of each eye were examined and the results averaged. The data were graphed ( Figs. 1 and 2). ResultsThe normal nuclei in the ONL appear uniform with a circular or slightly ovoid shape and contain many fine chromatin granules. Several layers of cone nuclei are concentrated at the fovea. Elsewhere in the macula cone nuclei are near the external limiting membrane and appear slightly larger and paler than the rod nuclei.

Age‐dependent normative values for differential luminance sensitivity in automated static perimetry using the Octopus 101

“…Marshall et al (1979) demonstrated a change with ageing in human photoreceptors, starting at the age of 40 years. Gartner & Henkind (1981) found that nuclei of photoreceptors from the outer nuclear layer were displaced into both the outer plexiform layer (increasing after 30 years of age and most pronounced after 50 years of age), and the layer of rods and cones (after 40 years of age and most commonly after 50 years of age). van Norren & van Meel (1985), who investigated the density of human cone pigments as a function of age, could not find any significant change in density up to 50 years of age.…”

“…Weale (1963), who originally ascribed the major portion of age-related VF DLS loss to preretinal factors, later suggested that the cell loss within the central optic pathway is the major factor in the age-related decline in sensitivity (Weale 1983). Many histological studies have shown that age-related reductions in photoreceptor density (Marshall et al 1979;Gartner & Henkind 1981;Dorey et al 1989;Gao & Hollyfield 1992;Curcio et al 1993), photopigment density (van Norren & van Meel 1985;Kilbride et al 1986), the number and morphology of optic nerve axons (Dolman et al 1980;Balazsi et al 1984;Sommer et al 1984;Repka & Quigley 1989) and the population density of neurons in the visual cortex (Devaney & Johnson 1980) do exist. Several studies have assumed a linear decrease in threshold values with age (Drance et al 1967a(Drance et al , 1967bEgge 1984;Flammer 1985;Brenton & Phelps 1986;Haas et al 1986;Jaffe et al 1986;Heijl et al 1987;Zulauf et al 1994a;Koller et al 2001;Okuyama et al 2001;Heijl 2005), whereas many authors have described a non-linear mathematical model or found a change point, demonstrating an increasing loss of sensitivity at a specific age (Derefeldt et al 1979;Iwase et al 1988;Vivell et al 1992;Lachenmayr et al 1994Lachenmayr et al , 2001Adams et al 1999;Lorch et al 2001;…”

Cone- and rod-mediated multifocal electroretinogram in early age-related maculopathy

“…Earlier histopathologic studies in ageing eyes also indicated preferential rod damage with elongation and nuclear displacement starting at age 40 years. 5,6 Holopigian et al 7 investigated the peripheral cone and rod function in subjects with early ARM by obtaining dark-adaptation curves, electro-oculograms (EOG), and full-field electroretinograms (ERG). They found no difference for the cones compared to agematched controls but abnormal absolute thresholds and cone-rod break times as well as impaired electroretinographic measures in the full-field ERG for the rod system.…”

Assessment of the Optical Contributions to the Age‐related Deterioration in Vision

“…In the retina, loss and displacement of photoreceptor cell nuclei occur (Gartner & Henkind, 1981) together with convolution of the outer portion of rod photoreceptor outer segments (Marshall, Grindle, Ansell & Borwein, 1979). Morphological changes in cone photoreceptor cells which subserve high acuity vision do not appear to have been studied except for dark-adaptation thresholds of cones which rise threefold from ages 20 to 80 years (Gunkel & Gouras, 1963).…”