Search

Measuring the color tuning of visual neurons is important for understanding the neural basis of vision, but it is challenging because of the inherently three-dimensional nature of color. Color tuning cannot be represented by a one-dimensional curve, and measuring three-dimensional tuning curves is difficult. One approach to addressing this challenge is to analyze neuronal color tuning data through the lens of mathematical models that make assumptions about the shapes of tuning curves. In this paper, we discuss the linear-nonlinear cascade model as a platform for measuring neuronal color tuning. We compare fitting this model by three techniques: two using response-weighted averaging and one using numerical optimization of likelihood. We highlight the advantages and disadvantages of each technique and emphasize the effects of the stimulus distribution on color tuning measurements., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Chromaticity type horizontal cells (C-type HCs) are the first retinal neurons exhibiting spectral information processing in cold-blooded vertebrates. The simple input of hyperpolarizing responses of cone photoreceptors is transformed in the C-type HCs into spectral opponent output. Nitric oxide (NO), a known background neuromodulator in the distal retina, was tested here for its effects upon spectral information processing by C-type HCs in the retina of turtle. Photoresponses were intracellularly recorded from C-type HCs, using light stimuli of different wavelength, applied over backgrounds of different wavelengths, and changing retinal NO level. Raising retinal level of NO in darkness by adding the precursor for its synthesis (l-Arginine) augmented the depolarizing photoresponses elicited by long-wavelength light stimuli, and reduced the hyperpolarizing photoresponses elicited by short-wavelength light stimuli. Lowering retinal level of NO by l-NAME, an inhibitor of NO synthesis, induced the opposite effects. However, the total voltage range of operation remained constant regardless of the level of NO. Qualitatively similar effects were observed under background illuminations regardless of background strength and wavelength. Altering retinal level of NO exerted a small effect upon the null wavelength. Our findings are consistent with the known effects of NO upon turtle distal retinal neurons, with the addition of NO strengthening the negative feedback pathway from L-type horizontal cells onto medium-wavelength cones., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Müller glia (MG) are major retinal supporting cells that participate in retinal metabolism, function, maintenance, and protection. During the pathogenesis of diabetic retinopathy (DR), a neurovascular disease and a leading cause of blindness, MG modulate vascular function and neuronal integrity by regulating the production of angiogenic and trophic factors. In this article, I will (1) briefly summarize our work on delineating the role and mechanism of MG-modulated vascular function through the production of vascular endothelial growth factor (VEGF) and on investigating VEGF signaling-mediated MG viability and neural protection in diabetic animal models, (2) explore the relationship among VEGF and neurotrophins in protecting Müller cells in in vitro models of diabetes and hypoxia and its potential implication to neuroprotection in DR and hypoxic retinal diseases, and (3) discuss the relevance of our work to the effectiveness and safety of long-term anti-VEGF therapies, a widely used strategy to combat DR, diabetic macular edema, neovascular age-related macular degeneration, retinopathy of prematurity, and other hypoxic retinal vascular disorders., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The complex pathology of diabetic retinopathy (DR) affects both vascular and neural tissue. The characteristics of neurodegeneration are well-described in animal models but have more recently been confirmed in the clinical setting, mostly by using non-invasive imaging approaches such as spectral domain optical coherence tomography (SD-OCT). The most frequent observations report loss of tissue in the nerve fiber layer and inner plexiform layer, confirming earlier findings from animal models. In several cases the reduction in inner retinal layers is reported in patients with little evidence of vascular lesions or macular edema, suggesting that degenerative loss of neural tissue in the inner retina can occur after relatively short durations of diabetes. Animal studies also suggest that neurodegeneration leading to retinal thinning is not limited to cell death and tissue loss but also includes changes in neuronal morphology, reduced synaptic protein expression and alterations in neurotransmission, including changes in expression of neurotransmitter receptors as well as neurotransmitter release, reuptake and metabolism. The concept of neurodegeneration as an early component of DR introduces the possibility to explore alternative therapies to prevent the onset of vision loss, including neuroprotective therapies and drugs targeting individual neurotransmitter systems, as well as more general neuroprotective approaches to preserve the integrity of the neural retina. In this review we consider some of the evidence for progressive retinal neurodegeneration in diabetes, and explore potential neuroprotective therapies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In the presence of optical blur at the fovea, blur adaptation can improve visual acuity (VA) and perceived image quality over time. However, little is known regarding blur adaptation in the peripheral retina. Here, we examined neural adaptation to myopic defocus at the fovea and parafovea (10° temporal retina) in both emmetropes and myopes. During a 60-min adaptation period, subjects (3 emmetropes and 3 myopes) watched movies with +2 diopters of defocus blur through a 6-mm artificial pupil in two separate, counter-balanced sessions for each retinal location. VA was measured at 10-min intervals under full aberration-corrected viewing using an adaptive optics (AO) vision simulator. By correcting subjects' native optical aberrations with AO, we bypassed the influence of the individual subjects' optical aberrations on visual performance. Overall, exhibited a small but significant improvement after the 60-min of adaptation at both the fovea (mean±SE VA improvement: -0.06±0.04 logMAR) and parafovea (mean±SE VA improvement: -0.07±0.04 logMAR). Myopic subjects exhibited significantly greater improvement in parafoveal VA (mean±SE VA improvement: 0.10±0.02 logMAR), than that of emmetropic subjects (mean±SE VA improvement: 0.04±0.03 logMAR). In contrast, there was no significant difference in foveal VA between the two refractive-error groups. In conclusion, our results reveal differences in peripheral blur adaptation between refractive-error groups, with myopes displaying a greater degree of adaptation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Our aim is to define related molecular events on how dormant Müller glia cells re-enter the cell cycle, proliferate and produce new retinal neurons from initial injury to glial scar formation. Sodium iodate (NaIO3) was used to induce acute retinal injury. Long-Evans rats were administered with NaIO3 or phosphate-buffered saline by intraperitoneal injection. The proliferation, dedifferentiation and neurogenesis of Müller cells were analyzed by double-labeled fluorescence immunohistochemistry with primary antibodies - against Müller cells and specific cell markers. Possible molecules that limit the regenerative potential of Müller cells were also determined by immunofluorescence staining, quantitative RT-PCR, protein array, ELISA and Western blot. In the first 3-7days after NaIO3 administration, Müller cells were activated and underwent a fate switch, including transient proliferation, dedifferentiation and neurogenesis. Nerve growth factor (NGF) signaling concomitantly increased with the downregulation of p27(Kip1) in Müller cells, which may promote Müller cells to re-enter the cell cycle. The transient increase of NGF signaling and the transient decrease of Notch signaling inhibited Hes1, which might enhance the neuronal differentiation of dedifferentiated Müller cells and suppress gliosis. Upregulated Notch and decreased NGF expressions limit dedifferentiation and neurogenesis, but induces retinal Müller cell gliosis at a later stage. We conclude that transient NGF upregulation and Notch1 downregulation may activate the transient proliferation, dedifferentiation and neurogenesis of Müller cells during NaIO3-induced acute retinal injury; which could be a therapeutic target for overcoming Müller cell gliosis. Such therapy could be potentially used for treating retinal-related diseases., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Our understanding of the development of the retina and visual pathways has seen enormous advances during the past 25years. New imaging technologies, coupled with advances in molecular biology, have permitted a fuller appreciation of the histotypical events associated with proliferation, fate determination, migration, differentiation, pathway navigation, target innervation, synaptogenesis and cell death, and in many instances, in understanding the genetic, molecular, cellular and activity-dependent mechanisms underlying those developmental changes. The present review considers those advances associated with the lineal relationships between retinal nerve cells, the production of retinal nerve cell diversity, the migration, patterning and differentiation of different types of retinal nerve cells, the determinants of the decussation pattern at the optic chiasm, the formation of the retinotopic map, and the establishment of ocular domains within the thalamus., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The effects of pharmacological blockade of the proximal retinal activity by N-methyl-D-aspartate (NMDA) on the V-log I function of the ERG b- and d-waves were studied in dark and light adapted frog eyes. The effects of NMDA depended on the type of photoreceptor input. In rod-dominated ERG the b-wave amplitude was decreased by NMDA, but that of the d-wave remained unchanged. In cone-dominated ERG the b-wave amplitude was increased while the d-wave amplitude was decreased. Thus, the b/d amplitude ratio was decreased in rod-dominated, but increased in cone-dominated ERG. Our results imply that the b/d amplitude ratio would be changed in an opposite way in the rod- and cone-dominated ERG, when the function of the proximal retinal neurons is compromised.

This article summarizes our recent works on stratum-by-stratum structure-function rules for synaptic contacts between retinal bipolar cells and third-order retinal neurons in the inner plexiform layer. These rules were derived from large-scale voltage clamp recordings of various types of bipolar cells in the tiger salamander retina, and they appear applicable to bipolar cells in the mouse and other mammalian species. This review also gives a brief account of how we used pathway-specific knockout mouse models to dissect rod and cone signaling channels in the mammalian retina. Furthermore, studies on cellular and genetic mechanisms underlying several neurodegenerative retinal disorders are described.