Contribution of parasol-magnocellular pathway ganglion cells to foveal retina in macaque monkey.

Parasol-magnocellular pathway ganglion cells form an important output stream of the primate retina and make a major contribution to visual motion detection. They are known to comprise ON and OFF type response polarities but the relative numbers of ON and OFF parasol cells, and the overall contribution of parasol cells to high-acuity foveal vision are not well understood. Here we use antibodies against carbonic anhydrase 8 (CA8) and intracellular injections of the liphilic dye DiI to show that CA8 selectively labels OFF parasol cells in macaque retina. By combined labeling with CA8 antibodies and a previously-described marker for parasol cells (GABAA receptor antibodies), we show that ON and OFF parasol cells each comprise âˆ¼ 6% of all ganglion cells in central retina (each peak density âˆ¼ 3000 cells/mm2 at 5 deg.), and each population comprises âˆ¼ 10% of all ganglion cells in peripheral temporal retina. Thus, the spatial density of parasol cells in central retina is greater than reported by previous anatomical studies, and the central-peripheral gradient in parasol cell density is shallower than previously reported. The data nevertheless predict decline in spatial acuity with visual field eccentricity for both midget-parvocellular pathway and parasol-magnocellular pathway mediated visual functions. The spatial resolving power of the OFF parasol array (peak âˆ¼ 7 cpd) falls short of macaque behavioral grating acuity by at least a factor of three throughout the retina.

Retinal ganglion cells expressing CaM kinase II in human and nonhuman primates.

Immunoreactivity for calcium-/calmodulin-dependent protein kinase II (CaMKII) in the primate dorsal lateral geniculate nucleus (dLGN) has been attributed to geniculocortical relay neurons and has also been suggested to arise from terminals of retinal ganglion cells. Here, we combined immunostaining with single-cell injections to investigate the expression of CaMKII in retinal ganglion cells of three primate species: macaque (Macaca fascicularis, M. nemestrina), human, and marmoset (Callithrix jacchus). We found that in all species, about 2%-10% of the total ganglion cell population expressed CaMKII. In all species, CaMKII was expressed by multiple types of wide-field ganglion cell including large sparse, giant sparse (melanopsin-expressing), broad thorny, and narrow thorny cells. Three other ganglion cells types, namely, inner and outer stratifying maze cells in macaque and tufted cells in marmoset were also found. Double labeling experiments showed that CaMKII-expressing cells included inner and outer stratifying melanopsin cells. Nearly all CaMKII-expressing ganglion cell types identified here are known to project to the koniocellular layers of the dLGN as well as to the superior colliculus. The best characterized koniocellular projecting cell type-the small bistratified (blue ON/yellow OFF) cell-was, however, not CaMKII-positive in any species. Our results indicate that the pattern of CaMKII expression in retinal ganglion cells is largely conserved across different species of primate suggesting a common functional role. But the results also show that CaMKII is not a marker for all koniocellular projecting retinal ganglion cells.

Satb1 expression in retinal ganglion cells of marmosets, macaques, and humans.

Recent advances in single-cell RNA sequencing have enabled the molecular distinction of ganglion cell populations in mammalian retinas. Here we used antibodies against the transcription factor special AT-rich binding protein 1 (Satb1, a protein which is expressed by on-off direction-selective ganglion cells in mouse retina) to study Satb1 expression in the retina of marmosets (Callithrix jacchus), macaques (Macaca fascicularis), and humans. In all species, Satb1 was exclusively expressed in retinal ganglion cells. The Satb1 cells made up ∼2% of the ganglion cell population in the central retina of all species, rising to a maximum ∼7% in peripheral marmoset retina. Intracellular injections in marmoset and macaque retinas revealed that most Satb1 expressing ganglion cells are widefield ganglion cells. In marmoset, Satb1 cells have a densely branching dendritic tree and include broad and narrow thorny, recursive bistratified, and parasol cells, all of which show some costratification with the outer or inner cholinergic amacrine cells. The recursive bistratified cells showed the strongest costratification but did not show extensive cofasciculation as reported for on-off direction-selective ganglion cells in rabbit and rodent retinas. In macaque, Satb1 was not expressed in recursive bistratified cells, but in large sparsely branching cells. Our findings further support the idea that the expression of transcription factors in retinal ganglion cells is not conserved across Old World (human and macaque) and New World (marmoset) primates and provides a further step to link a molecular marker with specific cell types.

Identification of retinal ganglion cell types expressing the transcription factor Satb2 in three primate species.

In primates, the retinal ganglion cells contributing to high acuity spatial vision (midget cells and parasol cells), and blue-yellow color vision (small bistratified cells) are well understood. Many other ganglion cell types with large dendritic fields (named wide-field ganglion cells) have been identified, but their spatial density and distribution are largely unknown. Here we took advantage of the recently established molecular diversity of ganglion cells to study wide-field ganglion cell populations in three primate species. We used antibodies against the transcription factor Special AT-rich binding protein 2 (Satb2) to explore its expression in macaque (Macaca fascicularis, M. nemestrina), human and marmoset (Callithrix jacchus) retinas. In all three species, Satb2 cells make up a low proportion (1.5-4%) of the ganglion cell population, with a slight increase from central to peripheral retina. Intracellular dye injections revealed that in macaque and human retinas, the large majority (over 80%) of Satb2 cells are inner and outer stratifying large sparse cells. By contrast, in marmoset retina the majority (over 60%) of Satb2 expressing cells were broad thorny cells, with smaller proportions of recursive bistratified (putative direction-selective), large bistratified, and outer stratifying narrow thorny cells. Our findings imply that Satb2 expression has undergone rapid species specific adaptations during primate evolution, because expression is not conserved across Old World (macaque, human) and New World (marmoset) suborders.

Melanopsin-expressing ganglion cells in human retina: Morphology, distribution, and synaptic connections.

Melanopsin-expressing retinal ganglion cells are intrinsically photosensitive cells that are involved in non-image forming visual processes such as the pupillary light reflex and circadian entrainment but also contribute to visual perception. Here we used immunohistochemistry to study the morphology, density, distribution, and synaptic connectivity of melanopsin-expressing ganglion cells in four post mortem human donor retinas. Two types of melanopsin-expressing ganglion cells were distinguished based on their dendritic stratification near either the outer or the inner border of the inner plexiform layer. Outer stratifying cells make up on average 60% of the melanopsin-expressing cells. About half of the melanopsin-expressing cells (or 80% of the outer stratifying cells) have their soma displaced to the inner nuclear layer. Inner stratifying cells have their soma exclusively in the ganglion cell layer and include a small proportion of bistratified cells. The dendritic field diameter of melanopsin-expressing cells ranges from 250 (near the fovea) to 1,000 µm in peripheral retina. The dendritic trees of outer stratifying cells cover the retina independent of soma location. The dendritic fields of both outer and inner stratifying cells show a high degree of overlap with a coverage factor of approximately two. Melanopsin-expressing cells occur at an average peak density of between ∼20 and ∼40 cells/mm2 at about 2 mm eccentricity, the density drops to below ∼10 cells/mm2 at about 8 mm eccentricity. Both the outer and inner stratifying dendrites express postsynaptic density (PSD95) immunoreactive puncta suggesting that they receive synaptic input from bipolar cells.

The eye in CHD.

In recent years, there has been a rise in the number patients with CHD surviving into adulthood. Many have complications related to their CHD or its treatments, outside the heart, including ocular abnormalities. The objective of this review is to highlight the ocular abnormalities that occur in adults with CHD, either from their condition or related to the common drugs prescribed to manage it. In particular, we reviewed the effects of cyanosis, coarctation of the aorta, endocarditis, and the side effects of Sildenafil and Amiodarone. A change in the retinal vasculature is a common observation with cyanosis or coarctation of the aorta. Occlusion of the retinal vessels may also be observed in cyanotic patients, as well as those with infectious endocarditis. Sildenafil has established ocular side effects; here they are explored in the context of therapy for pulmonary hypertension. Similarly, Amiodarone has established ocular risks, which are summarised. The high prevalence of ocular consequences in adult CHD patients reinforces the need for knowledge of the risks involved and for frequent ophthalmological screening where appropriate.

Management errors in adults with congenital heart disease: prevalence, sources, and consequences.

Aims: Improved survival has resulted in increasing numbers and complexity of adults with congenital heart disease (ACHD). International guidelines recommend specialized care but many patients are still not managed at dedicated ACHD centres. This study analysed referral sources and appropriateness of management for patients referred to our tertiary ACHD Centre over the past 3 years. Methods and results: We compared differences in care between patients referred from paediatric/ACHD-trained vs. general adult cardiologists, according to Adherence (A) or Non-Adherence (NA) with published guidelines. Non-Adherent cases were graded according to the severity of adverse outcome or risk of adverse outcome. Of 309 consecutively referred patients (28 ± 14 years, 51% male), 134 (43%) were from general cardiologists (19% highly complex CHD) and 115 (37%) were from paediatric cardiology or ACHD specialists (33% highly complex CHD). Sixty referrals (20%) were from other medical teams and of those, 31 had been lost to follow-up. Guideline deviations were more common in referrals from general compared to CHD-trained cardiologists (P < 0.001). Of general cardiology referrals, 49 (37%) were NA; 18 had catastrophic or major complications (n = 2, 16 respectively). In contrast, only 12 (10%) of the paediatric/ACHD referrals were NA, but none of these were catastrophic and only 3 were major. Simple, moderate, and highly complex CHD patients were at increased risk of adverse outcome when not under specialized CHD cardiology care (P = 0.04, 0.009, and 0.002, respectively). Conclusion: Non-adherence with guidelines was common in the ACHD population, and this frequently resulted in important adverse clinical consequences. These problems were more likely in patients who had not been receiving specialized CHD care. Configuring healthcare systems to optimize 'whole of life' care for this growing population is essential.