Browsing by Subject "Retina"

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  • Donner, Kristian; Yovanovich, Carola (2020)
    From the mid-19th century until the 1980's, frogs and toads provided important research models for many fundamental questions in visual neuroscience. In the present century, they have been largely neglected. Yet they are animals with highly developed vision, a complex retina built on the basic vertebrate plan, an accessible brain, and an experimentally useful behavioural repertoire. They also offer a rich diversity of species and life histories on a reasonably restricted physiological and evolutionary background. We suggest that important insights may be gained from revisiting classical questions in anurans with state-of-the-art methods. At the input to the system, this especially concerns the molecular evolution of visual pigments and photoreceptors, at the output, the relation between retinal signals, brain processing and behavioural decision-making.
  • Donner, K.; Grönholm, M.-L. (Elsevier, 1984)
    We have reexamined the receptive fields of frog retinal ganglion cells focussing on their surround properties. Carefully excluding artifacts due to stimulation of the (Gaussian) RF center, we found that spiking responses can be elicited by step stimulation of any receptor type in the surrounds of all the classes 1–4 Maturana et al. (1960) (J. gen. Physiol. 43, 129–175). The surround responses are antagonized by the responsive center and suppressed by the inhibitory surround, but are seen because of their slower dynamics. The responsive surround differs spectrally from the center: in the latter, cones and green rods compete, in the former, their signals sum.
  • Donner, K.; Koskelainen, A.; Djupsund, K.; Hemilä, S. (Elsevier, 1995)
    The kinetics of rod responses to flashes and steps of light was studied as a function of background intensity (IB) at the photoreceptor and ganglion cell levels in the frog retina. Responses of the rod photoreceptors were recorded intracellularly in the eyecup and as ERG mass potentials across the isolated, aspartate-superfused retina. The kinetics of the retinally transmitted signal was derived from the latencies of ganglion cell spike discharges recorded extracellularly in the eyecup. In all states of adaptation the linear-range rod response to dim flashes could be modelled as the impulse response of a chain of low-pass filters with the same number of stages: 4 (ERG) or 4–6 (intracellular). Dark-adapted time-to-peak (tp, mean ± SD) at 12°C was 2.4 ± 0.6 sec (ERG) or 1.7 ± 0.4 sec (intracellular). Under background light, the time scale shortened as a power function of background intensity, IB−b with b = 0.19±0.03 (ERG) or 0.14±0.04 (intracellular). The latency-derived time scale of the rod-driven signal at the ganglion cell agreed well with that of the photoreceptor responses. The apparent underlying impulse response had tp = 2.0±0.7 sec in darkness and accelerated as IB−b with b = 0.17±0.03. The photoreceptor-to-ganglion-cell transmission delay shortened by 30% between darkness and a background delivering ca 104 photoisomerizations per rod per second. Data from the literature suggest that all vertebrate photoreceptors may accelerate according to similar power functions of adapting intensity, with exponents in the range 0.1–0.2. It is noteworthy that the time scale of human (foveal) vision in experiments on flicker sensitivity and temporal summation shortens as a power function of mean luminance with b ≈ 0.15.
  • Bhattacharya, Madhushree; Sarkhel, Sanjay; Peltoniemi, Jonne; Broadbridge, Robert; Tuomainen, Marjo; Auriola, Seppo; Urtti, Arto (2017)
  • Djupsund, K.; Fyhrquist, N.; Hariyama, T.; Donner, K. (Elsevier, 1996)
    The threshold intensity for large-long incremental stimuli rises proportionally to adapting background luminance IB (Weber adaptation), but the intensity required to evoke a criterion high-brightness sensation rises much less steeply. We propose that this difference originates in the very first stage of visual processing, in the phototransduction and adaptation properties of the retinal photoreceptor cells. A physiological model previously found to account for visual latency and brightness as functions of stimulus intensity in the dark-adapted state [Donner, K. (1989). Visual Neuroscience, 3, 39–51] is extended to cover different states of adaptation. It is assumed that the neural coding of high intensities is based on the rate of rise (quasi-derivative) of the photoreceptor response just after it reaches a small threshold amplitude. The shallow background adaptation functions for high-brightness criteria emerge as a consequence of the relative constancy of the leading edge of large responses under backgrounds, a phenomenon that can be formally described by compensating changes in photoreceptor sensitivity and time scale. We first test the model on supra-threshold responses in the frog retina, where the discharge rate of ganglion cells (a possible neural code for brightness) and the primary rod hyperpolarizations can be recorded under identical conditions. The two are related as predicted over at least 3 log units of background intensity. We then show that published data on the background adaptation of human foveal high brightness judgments conform to the same model, assuming that human cones accelerate as IB−b with b = 0.14–0.15.
  • Govardovskii, V.I.; Fyhrquist, N.; Reuter, T.; Kuzmin, D.G.; Donner, K. (Cambridge University Press, 2000)
    Absorbance spectra were recorded by microspectrophotometry from 39 different rod and cone types representing amphibians, reptiles, and fishes, with A1- or A2-based visual pigments and [lambda]max ranging from 357 to 620 nm. The purpose was to investigate accuracy limits of putative universal templates for visual pigment absorbance spectra, and if possible to amend the templates to overcome the limitations. It was found that (1) the absorbance spectrum of frog rhodopsin extract very precisely parallels that of rod outer segments from the same individual, with only a slight hypsochromic shift in [lambda]max, hence templates based on extracts are valid for absorbance in situ; (2) a template based on the bovine rhodopsin extract data of Partridge and De Grip (1991) describes the absorbance of amphibian rod outer segments excellently, contrary to recent electrophysiological results; (3) the [lambda]max/[lambda] invariance of spectral shape fails for A1 pigments with small [lambda]max and for A2 pigments with large [lambda]max, but the deviations are systematic and can be readily incorporated into, for example, the Lamb (1995) template. We thus propose modified templates for the main “[alpha]-band” of A1 and A2 pigments and show that these describe both absorbance and spectral sensitivities of photoreceptors over the whole range of [lambda]max. Subtraction of the [alpha]-band from the full absorbance spectrum leaves a “[beta]-band” described by a [lambda]max-dependent Gaussian. We conclude that the idea of universal templates (one for A1- and one for A2-based visual pigments) remains valid and useful at the present level of accuracy of data on photoreceptor absorbance and sensitivity. The sum of our expressions for the [alpha]- and [beta]-band gives a good description for visual pigment spectra with [lambda]max > 350 nm.
  • Hemilä, S.; Lerber, T.; Donner, K. (Cambridge University Press, 1998)
    Noise recorded in visual neurons, or variability in psychophysical experiments, may be quantified in terms of quantal fluctuations from an “equivalent” steady illumination. The conversion requires assumptions concerning how photon signals are pooled in space and time, i.e. how to pass from light fluxes to numbers of photon events relevant to the Poisson statistics describing signal/noise. It is usual to approximate real weighting profiles for the integration of photon events in space and time (the sensitivity distribution of the receptive field [RF] and the waveform of the impulse response [IR]) by sharp-bordered apertures of “complete,” equal-weight summation of events. Apertures based on signal-equivalence cannot provide noise-equivalence, however, because greater numbers of events summed with smaller weights (as in reality) have lower variances than smaller numbers summed with full weight. Thus sharp-bordered apertures are necessarily smaller if defined for noise- than for signal-equivalence. We here consider the difference for some commonly encountered RF and IR profiles. Summation areas, expressed as numbers of photoreceptors (cones or rods) contributing with equal weight, are denoted NS for signal and NN for noise; sharply delimited summation times are correspondingly denoted tS and tN. We show that the relation in space is NN = 0.5NS for the Gaussian distribution (e.g. for the RF center mechanism of retinal ganglion cells). For a photoreceptor in an electrically coupled network the difference is even larger, e.g., for rods in the toad retina NN = 0.2NS (NS = 13.7 rods and NN = 2.8 rods). In time, the relation is tN [approximate] 0.7tS for realistic quantal response waveforms of photoreceptors. The surround input in a difference-of-Gaussians RF may either decrease or increase total noise, depending on the degree of correlation of center and surround noise. We introduce a third useful definition of sharp-bordered summation apertures: one that provides the same signal-to-noise ratio (SNR) for large-long stimuli as the real integration profiles. The SNR-equivalent summation area is N* = NS 2/NN and summation time t* = tS2/tN.
  • Helenius, Sune (University of Helsinki, 1992)
  • Koskelainen, A.; Donner, K.; Lerber, T.; Hemilä, S. (Elsevier, 1993)
    Mass cone photoresponses were recorded across the aspartate-treated frog retina under treatments chosen to affect putative pH-regulating mechanisms. The saturated response amplitude (Umax) was found to be a monotonically increasing function of perfusion pH in the range 7–8, and thus presumably of intracellular pH (pHi). Accepting that Umax can be used as an index of pH, changes, two results indicate the importance of bicarbonate transport for preventing intracellular acidification: (1) bicarbonate-buffered (6 mM HCO3− + 6 mM HEPES) perfusate increased Umax compared with nominally bicarbonate-free perfusate (12 mM HEPES); (2) the anion transport blocker DIDS (0.1 mM) caused a strong decrease in the amplitude of photoresponses. Substitution of 95 mM chloride by gluconate in the perfusing fluid boosted photoresponses indicating that at least part of the bicarbonate transport involves HCO3−/Cl− exchange. Amiloride (2mM) also caused a decrease of photoresponse amplitude, which suggests that Na+/H+ exchange contributes to pHi regulation. In all these respects, cones behaved similarly to rods. Cones differed from rods (in the intact retina) in that addition of 0.5 mM of the carbonic anhydrase inhibitor acetazolamide reduced (never augmented) photoresponses. The difference is considered in relation to the presence of carbonic anhydrase in cone, as opposed to rod, outer segments.
  • del Amo, Eva M.; Rimpelä, Anna-Kaisa Irmeli; Heikkinen, Emma; Kari, Otto K.; Ramsay, Eva; Lajunen, Tatu; Schmitt, Mechthild; Pelkonen, Laura; Bhattacharya, Madhushree; Richardson, Dominique; Subrizi, Astrid; Turunen, Tiina; Reinisalo, Mika; Itkonen, Jaakko; Toropainen, Elisa; Casteleijn, Marco G.; Kidron, Heidi; Antopolsky, Maxim; Vellonen, Kati-Sisko; Ruponen, Marika; Urtti, Arto (2017)
    Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.
  • Zeiner, Julian; Loukovaara, Sirpa; Losenkova, Karolina; Zuccarini, Mariachiara; Korhonen, Ani M.; Lehti, Kaisa; Kauppinen, Anu; Kaarniranta, Kai; Mueller, Christa E.; Jalkanen, Sirpa; Yegutkin, Gennady G. (2019)
    ATP and adenosine are important signaling molecules involved in vascular remodeling, retinal function, and neurovascular coupling in the eye. Current knowledge on enzymatic pathways governing the duration and magnitude of ocular purinergic signaling is incompletely understood. By employing sensitive analytical assays, this study dissected ocular purine homeostasis as a complex and coordinated network. Along with previously characterized ecto-5-nucleotidase/CD73 and adenylate kinase activities, other enzymes have been identified in vitreous fluids, including nucleoside triphosphate diphosphohydrolase (NTPDase), adenosine deaminase, and alkaline phosphatase. Strikingly, activities of soluble adenylate kinase, adenosine deaminase, ecto-5-nucleotidase/CD73, and alkaline phosphatase, as well as intravitreal concentrations of ATP and ADP, were concurrently upregulated in patients suffering from diabetic retinopathy (DR) with non-clearing vitreous hemorrhage (VH), when compared to DR eyes without VH and control eyes operated due to macular hole or pucker. Additional histochemical analysis revealed selective distribution of key ecto-nucleotidases (NTPDase1/CD39, NTPDase2, ecto-5-nucleotidase/CD73, and alkaline phosphatase) in the human sensory neuroretina and optic nerve head, and also in pathological neofibrovascular tissues surgically excised from patients with advanced proliferative DR. Collectively, these data provide evidence for specific hemorrhage-related shifts in purine homeostasis in DR eyes from the generation of anti-inflammatory adenosine towards a pro-inflammatory and pro-angiogenic ATP-regenerating phenotype. In the future, identifying the exact mechanisms by which a broad spectrum of soluble and membrane-bound enzymes coordinately regulates ocular purine levels and the further translation of purine-converting enzymes as potential therapeutic targets in the treatment of proliferative DR and other vitreoretinal diseases will be an area of intense interest.Key messagesNTPDase, alkaline phosphatase, and adenosine deaminase circulate in human vitreous.Purinergic enzymes are up-regulated in diabetic eyes with vitreous hemorrhage.Soluble adenylate kinase maintains high ATP levels in diabetic retinopathy eyes.Ecto-nucleotidases are co-expressed in the human retina and optic nerve head.Alkaline phosphatase is expressed on neovascular tissues excised from diabetic eyes.
  • Donner, K. (Elsevier, 1987)
    The sensitivity and intensity-response [R (log I)] functions of the receptive field center were determined by extracellular recording from frog retinal ganglion cells. The object was to study the steady-state adapting effects of peripheral background patterns: steady annuli and spinning “windmills” of light. Steady annular backgrounds could not be shown to directly effect any change of center responsiveness, only an enhancement of late response components attributable to depression of surround sensitivity. Movement of a windmill pattern shifted R(log I) functions to higher log intensities and decreased the maximal number of spikes in the response, but did not depress the saturation level of the impulse frequency. Its action thus resembled direct light-adaptation of the center.
  • Donner, Kristian (2021)
    Time is largely a hidden variable in vision. It is the condition for seeing interesting things such as spatial forms and patterns, colours and movements in the external world, and yet is not meant to be noticed in itself. Temporal aspects of visual processing have received comparatively little attention in research. Temporal properties have been made explicit mainly in measurements of resolution and integration in simple tasks such as detection of spatially homogeneous flicker or light pulses of varying duration. Only through a mechanistic understanding of their basis in retinal photoreceptors and circuits can such measures guide modelling of natural vision in different species and illuminate functional and evolutionary trade-offs. Temporal vision research would benefit from bridging traditions that speak different languages. Towards that goal, I here review studies from the fields of human psychophysics, retinal physiology and neuroethology, with a focus on fundamental constraints set by early vision.