Modeling the role of salience in the allocation of overt visual attention.

• We examined the histologic structure of the optic nerve head in 15 eyes of nine persons with a known glaucoma history. All had been seeing eyes, varying from normal visual acuity and visual field to advanced glaucoma damage. The site of damage to nerve fibers is the scleral lamina cribrosa, where there is local blockage of axonal transport. Early cup size increase prior to definite field loss results from loss of nerve fibers, not from damage to astrocytic glial cells of the nerve head. No selective damage to nerve head capillaries is seen in mildly damaged specimens. Scanning electron microscopic analysis suggests that the structure of the lamina cribrosa is an important determinant of the degree of susceptibility to damage by elevated intraocular pressure.

Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage.

Receptor-effector coupling by G proteins

Human colour vision depends on three classes of receptor, the short- (S), medium- (M), and long- (L) wavelength-sensitive cones. These cone classes are interleaved in a single mosaic so that, at each point in the retina, only a single class of cone samples the retinal image. As a consequence, observers with normal trichromatic colour vision are necessarily colour blind on a local spatial scale1. The limits this places on vision depend on the relative numbers and arrangement of cones. Although the topography of human S cones is known2,3, the human L- and M-cone submosaics have resisted analysis. Adaptive optics, a technique used to overcome blur in ground-based telescopes4, can also overcome blur in the eye, allowing the sharpest images ever taken of the living retina5. Here we combine adaptive optics and retinal densitometry6 to obtain what are, to our knowledge, the first images of the arrangement of S, M and L cones in the living human eye. The proportion of L to M cones is strikingly different in two male subjects, each of whom has normal colour vision. The mosaics of both subjects have large patches in which either M or L cones are missing. This arrangement reduces the eye's ability to recover colour variations of high spatial frequency in the environment but may improve the recovery of luminance variations of high spatial frequency.

The arrangement of the three cone classes in the living human eye

Visual perception in a blind subject with a chronic microelectronic retinal prosthesis

Objective: To determine the extent of preservation in the inner retina in retinitis pigmentosa (RP). Methods: We analyzed sectioned maculae of 21 postmortem eyes with RP and 19 age-matched, normal, postmortem eyes. Eyes were divided into 2 groups: severe and moderate RP. Cell nuclei were counted in the outer nuclear, inner nuclear, and ganglion cell layers within thirty 100-μm intervals from the foveola to 1500-μm eccentricity. Results: Statistically significant (P≤.05) loss of both the outer nuclear and ganglion cell layers was present in the groups with moderate and severe RP when compared with the control groups. However, even in the group with severe RP, 30% of the ganglion cells were histologically intact. Similarly, 78% and 88% of the inner nuclear layer cells were preserved in the groups with severe and moderate RP, respectively. Different inheritance modes showed no statistically significant differences in any of the retinal layers. Conclusions: Despite a statistically significant (P≤.05) loss of cells found in all retinal layers, a large percentage of the inner retinal neurons remained histologically intact. Current experimental therapies, such as photoreceptor transplantation and implantation of a visual prosthesis, are based on the premise that some inner retinal neurons are preserved after death of photoreceptors in RP. Our observations support this assumption.

Preservation of the Inner Retina in Retinitis Pigmentosa: A Morphometric Analysis

Primate cones maximally sensitive to short wavelength light (blue cones) have been previously identified by using indirect methods. We stained 7 wholemounted human retinas obtained from 6 female donors, using an affinity purified antibody to a 19 amino acid peptide sequence at the N-terminus of blue opsin (Lerea et al., '89: Neuron 3:367-376), standard PAP immunocytochemistry, and controls. Cones were counted where all outer segments could be traced to inner segments and were measured where cells were well aligned vertically. We find that: (1) 7% of cones within 4 mm of the foveal center are labeled by antiblue opsin; (2) compared to neighboring red/green cones, blue cone inner segments are 10% taller, have a larger cross-sectional diameter near the junction with the outer segment, and a smaller diameter near the external limiting membrane, resulting in a more cylindrical shape, (3) foveal blue cones are sparse, irregularly spaced, and missing in a zone about 100 microns (0.35 degrees) in diameter near the site of peak cone density, (4) the highest densities of blue cones (greater than 2,000 cells/mm2) are found in a ring at 0.1-0.3 mm eccentricity, and (5) the shortest distances between neighboring cones are between blue and red/green cones, and the blue and red/green mosaics are statistically independent. These findings are consistent with psychophysical reports of foveal tritanopia and maximum sensitivity to blue light at 1 degree eccentricity. Blue cone spacing may limit resolution of the blue channel out to 20-30 degrees eccentricity. The blue and red/green mosaics appear to be formed by separate processes.

Distribution and morphology of human cone photoreceptors stained with anti-blue opsin.

Transducin is a guanyl nucleotide-binding protein that couples rhodopsin photolysis to hydrolysis of guanosine 3',5'-monophosphate in rod photoreceptor cells of vertebrate retinas. Several complementary DNA clones encoding transducin subunits have recently been characterized. One clone, isolated from a bovine retina complementary DNA library, encodes a previously unidentified polypeptide with an amino acid sequence 78% identical to the sequence of the alpha subunit of bovine rod outer segment transducin. Antibodies to a synthetic peptide with amino acid sequence derived specifically from this novel polypeptide recognize a 41-kilodalton polypeptide in homogenates of bovine retina. Localization of this polypeptide in bovine retina by indirect immunofluorescence demonstrates that it is expressed only in cone outer segments. Antibodies to specific sequences found only in the rod transducin alpha subunit recognize a polypeptide localized only in the rod outer segment. Therefore, bovine rod and cone cells each express structurally related yet significantly different forms of transducin.

https://science.sciencemag.org/content/sci/234/4772/77.full.pdf

Identification of Specific Transducin α Subunits in Retinal Rod and Cone Photoreceptors

Radioautographic and cytochemical studies were performed at the ultrastructural level on the optic nerve heads of 21 Macaca fascicularis eyes with normal, elevated, or decreased intraocular pressures (IOP). Orthograde axoplasmic transport was labeled in all eyes by intravitreal injec- tions of a tritiated amino acid (leucine or proline) from 4 hr to 6 days before sacrifice. Retro- grade axoplasmic transport was labeled in most of the same eyes by injection of horseradish peroxidase (HRP) into one or both optic tracts and/or dorsal lateral geniculate nuclei (dLGN) from 12 to 24 hr before sacrifice. Electron microscopic studies were concentrated in the lamina scleralis (LS). Tritiated leucine was confined to axons in the nerve head in both normal and pathologic eyes. In hypertensive eyes both orthograde and retrograde transport appeared blocked initially in the posterior LS, then with increasing severity of injury appeared blocked and intermixed throughout the LS. In hypertensive eyes, collections of HRP were especially prominent within peripherally lying axons in bundles in the LS and on the posterior side of glial-scleral trabeculae in the LS. Hypotensive eyes (with papilledema) had similar, but much less severe, intra-axonal alterations of morphology and also demonstrated accumulations' of HRP in the LS. The morphologic alterations and blockage of axoplasmic transport within the LS in both hypertensive and hypotensive eyes appear to have resulted from mechanical com- pression of axonal bundles.

Radioautographic and cytochemical ultrastructural studies of axoplasmic transport in the monkey optic nerve head

Purpose. In an unpublished study, the authors found that immunoreactivity for basic fibroblast growth factor (bFGF) is increased in rod photoreceptors adjacent to long-standing laser burns in human diabetic retinas. The goal of this study was to determine whether laser photocoagulation produces a similar increase in photoreceptor bFGF and promotes survival of these cells in dystrophic rodent retinas. METHODS. Threshold (whitening) and subthreshold (nonwhitening) laser bums were made in retinas of normal and Royal College of Surgeons (RCS) rats and normal and rds mice. The retinas were processed for immunocytochemical and morphometric analyses. REsults. In nonlasered normal rat and mouse retinas, bFGF immunoreactivity was prominent in the nuclei of Muller cells and astrocytes. Photoreceptors were bFGF negative except for a zone of bFGF-immunoreactive rods near the ora serrata. Some photoreceptors in nonlasered retinas of RCS rats and rds mice became bFGF immunoreactive. After laser treatment, hFGF immunoreactivity was markedly increased in all photoreceptors flanking the threshold burns and within the subthreshold burns in normal and mutant rats and mice. In RCS rat retinas, photoreceptor bFGF immunoreactivity remained elevated within subthreshold burns and flanking the threshold burns, and photoreceptor survival was prolonged. In rds mouse retinas, increased bFGF immunoreactivity in photoreceptors was not sustained and their degeneration was not retarded. Conclusions. Laser treatment of RCS rat retinas produced a sustained increase in bFGF immunorcactivity in photoreceptors and prolonged their survival, but laser treatment of rds mouse retinas did not have a long-term effect on photoreceptor bFGF immunoreactivity or survival. Although species differences in laser effects on photoreceptor bFGF and survival are apparent, the finding that rods flanking laser burns in human retinas have sustained increases in hFGF immunoreactivity suggests that laser treatment may be useful for prolonging survival of mutant photoreceptors in retinas of patients with retinitis pigmentosa.

Ingrid B. Klock

Papers

Preservation of the Inner Retina in Retinitis Pigmentosa: A Morphometric Analysis

Distribution and morphology of human cone photoreceptors stained with anti-blue opsin.

Identification of Specific Transducin α Subunits in Retinal Rod and Cone Photoreceptors

Radioautographic and cytochemical ultrastructural studies of axoplasmic transport in the monkey optic nerve head

Effects of retinal laser photocoagulation on photoreceptor basic fibroblast growth factor and survival.