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Lack of cone mediated retinal function increases susceptibility to form-deprivation myopia in mice
摘要： Retinal photoreceptors are important in visual signaling for normal eye growth in animals. We used Gnat2 cplf3/cplf3 (Gnat2-/-) mice, a genetic mouse model of cone dysfunction to investigate the influence of cone signaling in ocular refractive development and myopia susceptibility in mice. Refractive development under normal visual conditions was measured for Gnat2-/- and age-matched Gnat2+/+ mice, every 2 weeks from 4 to 14 weeks of age. Weekly measurements were performed on a separate cohort of mice that underwent monocular form-deprivation (FD) in the right eye from 4 weeks of age using head-mounted diffusers. Refraction, corneal curvature, and ocular biometrics were obtained using photorefraction, keratometry and optical coherence tomography, respectively. Retinas from FD mice were harvested, and analyzed for dopamine (DA) and 3,4-dihydroxyphenylacetate (DOPAC) using high-performance liquid chromatography. Under normal visual conditions, Gnat2+/+ and Gnat2-/- mice showed similar refractive error, axial length, and corneal radii across development (p>0.05), indicating no significant effects of the Gnat2 mutation on normal ocular refractive development in mice. Three weeks of FD produced a significantly greater myopic shift in Gnat2-/- mice compared to Gnat2+/+ controls (-5.40 ± 1.33 D vs -2.28 ± 0.28 D, p=0.042). Neither the Gnat2 mutation nor FD altered retinal levels of DA or DOPAC. Our results indicate that cone pathways needed for high acuity vision in primates are not as critical for normal refractive development in mice, and that both rods and cones contribute to visual signalling pathways needed to respond to FD in mammalian eyes.
关键词： mouse,form-deprivation,dopamine,Gnat2,Refractive error,cone photoreceptors
更新于2025-09-23 15:23:52
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Localizing proton-mediated inhibitory feedback at the retinal horizontal cell-cone synapse with genetically-encoded pH probes
摘要： Lateral inhibition in the vertebrate retina depends on a negative feedback synapse between horizontal cells (HCs) and rod and cone photoreceptors. A change in pH is thought to be the signal for negative feedback, but its spatial profile in the synaptic cleft is unknown. Here we use 3 different membrane proteins, each fused to the same genetically-encoded pH-sensitive GFP (pHluorin), to probe synaptic pH in retina from transgenic zebrafish (Danio rerio) of either sex. We used the cone transducin promoter to express SynaptopHluorin (pHluorin on VAMP2) or CalipHluorin (pHluorin on an L-type Ca2+ channel) and the HC-specific connexin-55.5 promoter to express AMPApHluorin (pHluorin on an AMPA receptor). Stimulus light led to increased fluorescence of all three probes, consistent with alkalinization of the synaptic cleft. The receptive field size, sensitivity to surround illumination, and response to activation of an alien receptor expressed exclusively in HCs, are consistent with lateral inhibition as the trigger for alkalinization. However, SynaptopHluorin and AMPApHluorin, which are displaced farther from cone synaptic ribbons than CalipHlourin, reported a smaller pH change. Hence, unlike feed-forward glutamatergic transmission, which spills over to allow cross-talk between terminals in the cone network, the pH change underlying HC feedback is compartmentalized to individual synaptic invaginations within a cone terminal, consistent with private line communication.
关键词： lateral inhibition,zebrafish,cone photoreceptors,pHluorin,horizontal cells,synaptic pH,retina
更新于2025-09-11 14:15:04
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Endogenous Fluorophores Enable Two-Photon Imaging of the Primate Eye
摘要： Noninvasive two-photon imaging of a living mammalian eye can reveal details of molecular processes in the retina and RPE. Retinyl esters and all-trans-retinal condensation products are two types of retinoid fluorophores present in these tissues. We measured the content of these two types of retinoids in monkey and human eyes to validate the potential of two-photon imaging for monitoring retinoid changes in human eyes.
关键词： primate retina,retinoid cycle,two-photon microscopy,rod photoreceptors,cone photoreceptors
更新于2025-09-09 09:28:46