Diabetic mice have retinal and choroidal blood flow deficits and electroretinogram deficits with impaired responses to hypercapnia.

Purpose: The purpose of this study was to investigate neuronal and vascular functional deficits in the retina and their association in a diabetic mouse model. We measured electroretinography (ERG) responses and choroidal and retinal blood flow (ChBF, RBF) with magnetic resonance imaging (MRI) in healthy and diabetic mice under basal conditions and under hypercapnic challenge.

Methods: Ins2Akita diabetic (Diab, n = 8) and age-matched, wild-type C57BL/6J mice (Ctrl, n = 8) were studied under room air and moderate hypercapnia (5% CO2).

Correlation of Retinal Structure and Visual Function Assessments in Mouse Diabetes Models.

Purpose: Diabetic retinopathy results in vision loss with changes to both retinal blood vessels and neural retina. Recent studies have revealed that animal models of diabetes demonstrate early loss of visual function. We explored the time course of retinal change in three different mouse models of diabetes in a longitudinal study using in vivo measures of retinal structure (optical coherence tomography [OCT]) and visual function (optomotor and pupillary responses).

Measures of Healthspan as Indices of Aging in Mice-A Recommendation.

Over the past decade, a large number of discoveries have shown that interventions (genetic, pharmacological, and nutritional) increase the lifespan of invertebrates and laboratory rodents. Therefore, the possibility of developing antiaging interventions for humans has gone from a dream to a reality. However, it has also become apparent that we need more information than just lifespan to evaluate the translational potential of any proposed antiaging intervention to humans.

Dark rearing alters the normal development of spatiotemporal response properties but not of contrast detection threshold in mouse retinal ganglion cells.

The mouse visual system is immature when the eyes open two weeks after birth. As in other mammals, some of the maturation that occurs in the subsequent weeks is known to depend on visual experience. Development of the retina, which as the first stage of vision provides the visual information to the brain, also depends on light-driven activity for proper development but has been less well studied than visual cortical development.

Reduced ocular blood flow as an early indicator of diabetic retinopathy in a mouse model of diabetes.

Purpose: To investigate ocular blood flow and visual function in the Ins2(Akita) diabetic retinopathy mouse model at early and late time points after onset of hyperglycemia.

Methods: Mice heterozygous for the Ins2(Akita) mutation, which become hyperglycemic at approximately 4 weeks old, were studied at 2.5 and 7.

Spatial frequency threshold and contrast sensitivity of an optomotor behavior are impaired in the Ins2Akita mouse model of diabetes.

Diabetic retinopathy can lead to progressive loss of vision and is a leading cause of blindness. The Ins2(Akita) mouse model of diabetes develops significant retinal and systemic pathology, but how these affect visual behavior is unknown. Here, we show that Ins2(Akita) mice have progressive, quantifiable vision deficits in an optomotor behavior.

Missing optomotor head-turning reflex in the DBA/2J mouse.

Purpose: The optomotor reflex of DBA/2J (D2), DBA/2J-Gpnmb+ (D2-Gpnmb+), and C57BL/6J (B6) mouse strains was assayed, and the retinal ganglion cell (RGC) firing patterns, direction selectivity, vestibulomotor function and central vision was compared between the D2 and B6 mouse lines.

Methods: Intraocular pressure (IOP) measurements, real-time PCR, and immunohistochemical analysis were used to assess the time course of glaucomatous changes in D2 retinas. Behavioral analyses of optomotor head-turning reflex, visible platform Morris water maze and Rotarod measurements were conducted to test vision and vestibulomotor function.

Receptive field center size decreases and firing properties mature in ON and OFF retinal ganglion cells after eye opening in the mouse.

Development of the mammalian visual system is not complete at birth but continues postnatally well after eye opening. Although numerous studies have revealed changes in the development of the thalamus and visual cortex during this time, less is known about the development of response properties of retinal ganglion cells (RGCs). Here, we mapped functional receptive fields of mouse RGCs using a Gaussian white noise checkerboard stimulus and a multielectrode array to record from retinas at eye opening, 3 days later, and 4 wk after birth, when visual responses are essentially mature.

The polymodal ion channel transient receptor potential vanilloid 4 modulates calcium flux, spiking rate, and apoptosis of mouse retinal ganglion cells.

Sustained increase in intraocular pressure represents a major risk factor for eye disease, yet the cellular mechanisms of pressure transduction in the posterior eye are essentially unknown. Here we show that the mouse retina expresses mRNA and protein for the polymodal transient receptor potential vanilloid 4 (TRPV4) cation channel known to mediate osmotransduction and mechanotransduction. TRPV4 antibodies labeled perikarya, axons, and dendrites of retinal ganglion cells (RGCs) and intensely immunostained the optic nerve head.

Melanopsin-dependent light avoidance in neonatal mice.

Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) form a light-sensitive system separate from rods and cones. Direct light stimulation of ipRGCs can regulate many nonimage-forming visual functions such as photoentrainment of circadian rhythms and pupil responses, and can intensify migraine headache in adults. In mice, ipRGCs are light responsive as early as the day of birth.

Brain-derived neurotrophic factor and TrkB modulate visual experience-dependent refinement of neuronal pathways in retina.

Sensory experience refines neuronal structure and functionality. The visual system has proved to be a productive model system to study this plasticity. In the neonatal retina, the dendritic arbors of a large proportion of ganglion cells are diffuse in the inner plexiform layer.

Vesicular glutamate transporter 1 is required for photoreceptor synaptic signaling but not for intrinsic visual functions.

Glutamatergic neurotransmission requires vesicular glutamate transporters (VGLUTs) to sequester glutamate into synaptic vesicles. Generally, VGLUT1 and VGLUT2 isoforms show complementary expression in the CNS and retina. However, little is known about whether isoform-specific expression serves distinct pathways and physiological functions.

Intrinsic ON responses of the retinal OFF pathway are suppressed by the ON pathway.

Parallel ON and OFF pathways conduct visual signals from bipolar cells in the retina to higher centers in the brain. ON responses are thought to originate by exclusive use of metabotropic glutamate receptor 6 (mGluR6) expressed in retinal ON bipolar cells. Paradoxically, we find ON responses in retinal ganglion cells of mGluR6-null mice, but they occur at long latency.

Neuronal pentraxins mediate synaptic refinement in the developing visual system.

Neuronal pentraxins (NPs) define a family of proteins that are homologous to C-reactive and acute-phase proteins in the immune system and have been hypothesized to be involved in activity-dependent synaptic plasticity. To investigate the role of NPs in vivo, we generated mice that lack one, two, or all three NPs. NP1/2 knock-out mice exhibited defects in the segregation of eye-specific retinal ganglion cell (RGC) projections to the dorsal lateral geniculate nucleus, a process that involves activity-dependent synapse formation and elimination.

Development of precise maps in visual cortex requires patterned spontaneous activity in the retina.

The visual cortex is organized into retinotopic maps that preserve an orderly representation of the visual world, achieved by topographically precise inputs from the lateral geniculate nucleus. We show here that geniculocortical mapping is imprecise when the waves of spontaneous activity in the retina during the first postnatal week are disrupted genetically. This anatomical mapping defect is present by postnatal day 8 and has functional consequences, as revealed by optical imaging and microelectrode recording in adults.

Ontogeny of plasma membrane Ca2+ ATPase isoforms in the neural retina of the postnatal rat.

Calcium ion (Ca(2+)) signaling has been widely implicated in developmental events in the retina, but little is known about the specific mechanisms utilized by developing neurons to decrease intracellular Ca(2+). Using immunocytochemistry, we determined the expression profiles of all known isoforms of a key Ca(2+) transporter, the plasma membrane Ca(2+) ATPase (PMCA), in the rat retina. During the first postnatal week, the four PMCA isoforms were expressed in patterns that differed from their expression in the adult retina.

Ephrin-As and neural activity are required for eye-specific patterning during retinogeniculate mapping.

In mammals, retinal ganglion cell (RGC) projections initially intermingle and then segregate into a stereotyped pattern of eye-specific layers in the dorsal lateral geniculate nucleus (dLGN). Here we found that in mice deficient for ephrin-A2, ephrin-A3 and ephrin-A5, eye-specific inputs segregated but the shape and location of eye-specific layers were profoundly disrupted. In contrast, mice that lacked correlated retinal activity did not segregate eye-specific inputs.

Need rods? Get glycine receptors and taurine.

Taurine, a multifunctional amino acid prevalent in developing nervous tissues, regulates the number of rod photoreceptors in developing postnatal rodent retina. In this issue of Neuron, Young and Cepko show that taurine acts via GlyRalpha2 subunit-containing glycine receptors expressed by retinal progenitor cells at birth.