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Assessment of Different Sampling Methods for Measuring and Representing Macular Cone Density Using Flood-Illuminated Adaptive Optics
摘要： PURPOSE. To describe a standardized flood-illuminated adaptive optics (AO) imaging protocol suitable for the clinical setting and to assess sampling methods for measuring cone density. METHODS. Cone density was calculated following three measurement protocols: 50 × 50-μm sampling window values every 0.5° along the horizontal and vertical meridians (fixed-interval method), the mean density of expanding 0.5°-wide arcuate areas in the nasal, temporal, superior, and inferior quadrants (arcuate mean method), and the peak cone density of a 50 × 50-μm sampling window within expanding arcuate areas near the meridian (peak density method). Repeated imaging was performed in nine subjects to determine intersession repeatability of cone density. RESULTS. Cone density montages could be created for 67 of the 74 subjects. Image quality was determined to be adequate for automated cone counting for 35 (52%) of the 67 subjects. We found that cone density varied with different sampling methods and regions tested. In the nasal and temporal quadrants, peak density most closely resembled histological data, whereas the arcuate mean and fixed-interval methods tended to underestimate the density compared with histological data. However, in the inferior and superior quadrants, arcuate mean and fixed-interval methods most closely matched histological data, whereas the peak density method overestimated cone density compared with histological data. Intersession repeatability testing showed that repeatability was greatest when sampling by arcuate mean and lowest when sampling by fixed interval. CONCLUSIONS. We show that different methods of sampling can significantly affect cone density measurements. Therefore, care must be taken when interpreting cone density results, even in a normal population.
关键词： cone photoreceptor density,retina,adaptive optics
更新于2025-09-23 15:23:52
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Photoreceptor Progenitors Depend Upon Coordination of <i>gdf6a</i> , <i>thrβ</i> , and <i>tbx2b</i> to Generate Precise Populations of Cone Photoreceptor Subtypes
摘要： PURPOSE. Replacing cone photoreceptors, the units of the retina necessary for daytime vision, depends upon the successful production of a full variety of new cones from, for example, stem cells. Using genetic experiments in a model organism with high cone diversity, zebrafish, we map the intersecting effects of cone development factors gdf6a, tbx2b, and thrb. METHODS. We investigated these genes of interest by using genetic combinations of mutants, gene knockdown, and dominant negative gene expression, and then quantified cone subtype outcomes (which normally develop in tightly regulated ratios). RESULTS. Gdf6a mutants have reduced blue cones and, discovered here, reduced red cones. In combined gdf6a/tbx2b disruption, the loss of gdf6a in heterozygous tbx2b mutants reduced UV cones. Intriguingly, when we disrupted thrb in gdf6a mutants by using a thrb morpholino, their combined early disruption revealed a lamination phenotype. Disrupting thrb activity via expression of a dominant negative thrb (dnthrb) at either early or late retinal development had differential outcomes on red cones (reduced abundance), versus UV and blue cones (increased abundance). By using dnthrb in gdf6a mutants, we revealed that disrupting thrb activity did not change gdf6a mutant cone phenotypes. CONCLUSIONS. Gdf6a loss directly affects blue and red cones and indirectly affects UV cones by increasing sensitivity to additional disruption, such as reduced tbx2b, resulting in fewer UV cones. The effects of thrb change through photoreceptor development, first promoting red cones and restricting UV cones, and later restricting UV and blue cones. The effects of gdf6a on UV, blue, and red cone development overlap with, but likely supersede, those of thrb.
关键词： BMP signaling,progenitor,color vision,retinal lamination,thyroid signaling,zebrafish,retinal development,determination,regeneration,cone photoreceptor
更新于2025-09-19 17:15:36
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Induction of rod versus cone photoreceptor-specific progenitors from retinal precursor cells
摘要： During development, multipotent progenitors undergo temporally-restricted differentiation into post-mitotic retinal cells; however, the mechanisms of progenitor division that occurs during retinogenesis remain controversial. Using clonal analyses (lineage tracing and single cell cultures), we identify rod versus cone lineage-specific progenitors derived from both adult retinal stem cells and embryonic neural retinal precursors. Taurine and retinoic acid are shown to act in an instructive and lineage-restricted manner early in the progenitor lineage hierarchy to produce rod-restricted progenitors from stem cell progeny. We also identify an instructive, but lineage-independent, mechanism for the specification of cone-restricted progenitors through the suppression of multiple differentiation signaling pathways. These data indicate that exogenous signals play critical roles in directing lineage decisions and resulting in fate-restricted rod or cone photoreceptor progenitors in culture. Additional factors may be involved in governing photoreceptor fates in vivo.
关键词： Retina,Rod photoreceptor,Cone photoreceptor,Stem cell,Progenitors
更新于2025-09-09 09:28:46
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Signal transmission at invaginating cone photoreceptor synaptic contacts following deletion of the presynaptic cytomatrix protein Bassoon in mouse retina
摘要： A key feature of the mammalian retina is the segregation of visual information in parallel pathways, starting at the photoreceptor terminals. Cone photoreceptors establish synaptic contacts with On bipolar and horizontal cells at invaginating, ribbon-containing synaptic sites, whereas Off bipolar cells form flat, non-ribbon-containing contacts. The cytomatrix protein Bassoon anchors ribbons at the active zone, and its absence induces detachment of ribbons from the active zone. In this study we investigate the impact of a missing Bassoon on synaptic transmission at the first synapse of the visual system. Release properties of cone photoreceptors were studied in wild-type and mutant mouse retinae with a genetic disruption of the presynaptic cytomatrix protein Bassoon using whole-cell voltage-clamp recordings. Light and electron microscopy revealed the distribution of Ca2+ channels and synaptic vesicles, respectively, in both mouse lines. Whole-cell recordings from postsynaptic horizontal cells of the two mouse lines showed that the presence of Bassoon (and a ribbon) enhanced the rate of exocytosis during tonic and evoked release by increasing synaptic vesicle pool size and replenishment rate, while at the same time slowing synaptic vesicle release. Furthermore, the number of Cav1.4 channels and synaptic vesicles was significantly higher at wild-type than at Bassoon mutant synaptic sites. The results of our study demonstrate that glutamate release from cone photoreceptor terminals can occur independent of a synaptic ribbon, but seems restricted to active zones, and they show the importance of a the synaptic ribbon in sustained and spatially and temporally synchronized neurotransmitter release.
关键词： signal transmission,retina,cone photoreceptor,horizontal cell,ribbon synapse,Bassoon
更新于2025-09-09 09:28:46