Publications by authors named "Sammy Lee"

Background: Genetic biocontrol interventions targeting mosquito-borne diseases require the release of male mosquitoes exclusively, as only females consume blood and transmit pathogens. Releasing only males eliminates the risk of increasing mosquito bites and spreading pathogens while enabling effective population control. The aim of this study is to develop robust sex-sorting methods for early larval stages in mosquitoes, enabling scalable male-only releases for genetic biocontrol interventions.

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Article Synopsis
  • The transcription factors Foxp1 and Foxp2 are found in small subgroups of retinal ganglion cells in marmoset monkeys, similar to their expression in mice.
  • DiI injections showed that these cells comprise different types, including tufted and thorny cells; tufted cells were most common among Foxp2-expressing ones.
  • Only a small number of these Foxp-expressing cells also express calretinin, indicating a distinction between these markers in marmoset retinal ganglion cells.
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Genetic biocontrol interventions targeting mosquito-borne diseases require the release of male mosquitoes exclusively, as only females consume blood and transmit human pathogens. This reduces the risk of spreading pathogens while enabling effective population control. Robust sex sorting methods to enable early larval sorting in mosquitoes need to be developed to allow for scalable sex sorting for genetic biocontrol interventions.

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The loss or dysfunction of human corneal endothelial cells (hCEnCs) is a leading cause of blindness due to corneal failure. Corneal transplantation with a healthy donor cornea has been the only available treatment for corneal endothelial disease. However, the need for way to regenerate the CEnCs has been increased due to the global shortage of donor corneas.

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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.

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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).

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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.

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Purpose: The purpose of this study was to measure the composition of the inner nuclear layer (INL) in the central and peripheral human retina as foundation data for interpreting INL function and dysfunction.

Methods: Six postmortem human donor retinas (male and female, aged 31-56 years) were sectioned along the temporal horizontal meridian. Sections were processed with immunofluorescent markers and imaged using high-resolution, multichannel fluorescence microscopy.

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We determined the retinal ganglion cell types projecting to the medial subdivision of inferior pulvinar (PIm) and the superior colliculus (SC) in the common marmoset monkey, Callithrix jacchus. Adult marmosets received a bidirectional tracer cocktail into the PIm (conjugated to Alexa fluor 488), and the SC (conjugated to Alexa fluor 594) using an MRI-guided approach. One SC injection included the pretectum.

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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.

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In primate retina, the calcium-binding protein calbindin is expressed by a variety of neurons including cones, bipolar cells, and amacrine cells but it is not known which type(s) of cell express calbindin in the ganglion cell layer. The present study aimed to identify calbindin-positive cell type(s) in the amacrine and ganglion cell layer of human and marmoset retina using immunohistochemical markers for ganglion cells (RBPMS and melanopsin) and cholinergic amacrine (ChAT) cells. Intracellular injections following immunolabeling was used to reveal the morphology of calbindin-positive cells.

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Purpose: The objective of this study was to map the distribution and density of the three major components of the classical scotopic "night vision" pathway (rods, rod bipolar, and AII amacrine cells) in postmortem human retinas.

Methods: Four postmortem donor eyes (male and female, aged 44-56 years) were used to cut vertical sections through the temporal horizontal meridian. The sections were processed for immunohistochemistry and imaged using high-resolution multichannel confocal microscopy.

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Purpose: Particle-mediated gene transfer has been used in animal models to study the morphology and connectivity of retinal ganglion cells. The aim of the present study was to apply this method to transfect ganglion cells in postmortem human retina.

Methods: Postmortem human eyes from male and female donors aged 40 to 76 years old were obtained within 15 hours after death.

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The primate visual brain possesses a myriad of pathways, whereby visual information originating at the retina is transmitted to multiple subcortical areas in parallel, before being relayed onto the visual cortex. The dominant retinogeniculostriate pathway has been an area of extensive study, and Vivien Casagrande's work in examining the once overlooked koniocellular pathway of the lateral geniculate nucleus has generated interest in how alternate subcortical pathways can contribute to visual perception. Another subcortical visual relay center is the inferior pulvinar (PI), which has four subdivisions and numerous connections with other subcortical and cortical areas and is directly recipient of retinal afferents.

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In primates, over 17 morphological types of retinal ganglion cell have been distinguished by their dendritic morphology and stratification, but reliable markers for specific ganglion cell populations are still rare. The calcium binding protein calretinin is known to be expressed in the inner nuclear and the ganglion cell layer of marmoset retina, however, the specific cell type(s) expressing calretinin in the ganglion cell layer are yet to be determined. Here, we identified calretinin positive retinal ganglion cells in the common marmoset Callithrix jacchus.

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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.

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Retinal bipolar cells spread their dendritic arbors to tile the retinal surface, extending them to the tips of the dendritic fields of their homotypic neighbors, minimizing dendritic overlap. Such uniform nonredundant dendritic coverage of these populations would suggest a degree of spatial order in the properties of their somal distributions, yet few studies have examined the patterning in retinal bipolar cell mosaics. The present study examined the organization of two types of cone bipolar cells in the mouse retina, the Type 2 cells and the Type 4 cells, and compared their spatial statistical properties with those of the horizontal cells and the cholinergic amacrine cells, as well as to random simulations of cells matched in density and constrained by soma size.

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Antibodies against calretinin are markers for one type of rod pathway interneuron (AⅡ amacrine cell) in the retina of some but not all mammalian species. The AⅡ cells play a crucial role in night-time (scotopic) vision and have been proposed as a target for optogenetic restoration of vision in retinal disease. In the present study we aimed to characterize the AⅡ cells in human retina.

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Amacrine cells comprise ∼ 30 morphological types in the mammalian retina. The synaptic connectivity and function of a few γ-aminobutyric acid (GABA)ergic wide-field amacrine cells have recently been studied; however, with the exception of the rod pathway-specific AII amacrine cell, the connectivity of glycinergic small-field amacrine cells has not been investigated in the mouse retina. Here, we studied the morphology and connectivity pattern of the small-field A8 amacrine cell.

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The retina consists of ordered arrays of individual types of neurons for processing vision. Here, we show that such order is necessary for intrinsically photosensitive retinal ganglion cells (ipRGCs) to function as irradiance detectors. We found that during development, ipRGCs undergo proximity-dependent Bax-mediated apoptosis.

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Individual types of retinal neurons are distributed to minimize proximity to neighboring cells. Many of these same cell types extend dendrites to provide coverage of the retinal surface. These two cardinal features of retinal mosaics are disrupted, for certain cell types, in mice deficient for the Down syndrome cell adhesion molecule, Dscam, exhibiting an aberrant clustering of somata and fasciculation of dendrites.

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The establishment of neuronal circuitry during development relies upon the action of cell-intrinsic mechanisms that specify neuronal form as well as plastic processes that require the transmission of neural activity between afferents and their targets. Here, we examine the role of interactions between neighboring like-type cells within the mouse retina upon neuronal differentiation and circuit formation. Two different genetically modified mouse models were used to modulate the density of homotypic neighbors, the Type 7 cone bipolar cells, without affecting the density of their afferents, the cone photoreceptors.

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Developing retinal neurons differentiate their distinctive dendritic morphologies through cell-intrinsic instructions and cellular interactions within the local environment. This review examines the contributions of interactions with afferents and with homotypic neighbors upon the dendritic morphogenesis of retinal bipolar cells in four different mouse models that modulate the frequency of these interactions. Comparisons with horizontal cell differentiation are discussed, and differences between the dendritic plasticity within the outer versus inner plexiform layers are highlighted.

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Two morphological types of melanopsin-expressing ganglion cells have been described in primate retina. Both types show intrinsic light responses as well as rod- and cone-driven ON-type responses. Outer stratifying cells have their dendrites close to the inner nuclear layer (OFF sublamina); inner stratifying cells have their dendrites close to the ganglion cell layer (ON sublamina).

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The midget-parvocellular pathway in foveal retina of primates shows a "private line" (one-to-one) connectivity with cone photoreceptors. The connectivity of this pathway outside the fovea is not well understood. Here, we studied the population of OFF midget bipolar cells across the retinae of marmoset monkeys (Callithrix jacchus) by using light microscopy.

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