Stratified organization and disorganization of inner plexiform layer revealed by TNAP activity in healthy and diabetic rat retina

Kántor, Orsolya; Varga, Alexandra; Toth, R. A.; Énzsöly, Anna; Pálfi, Emese; Kovács-Öller, Tamás; Nitschke, Roland; Szél, Ágoston; Székely, Andrea; Völgyi, Béla; Négyessy, László; Somogyvári, Zoltán; Lukáts, Ákos

doi:10.1007/s00441-014-2047-x

Cited by 8 publications

(6 citation statements)

References 40 publications

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“…The anti-Ank-G anti-PanNa v and anti-TH and antibodies have been utilized in previous publications to respectively identify AIS (Ank-G and PanNa v ) and dopaminergic structures (TH), as cited in Table 1. Our results showed the expected neuronal labeling patterns, as based on the literature using these or other anti-Ank-G (Puthussery, Venkataramani, Gayet-Primo, Smith, & Taylor, 2013;Van Wart, Trimmer, & Matthews, 2007;Wang & Sun, 2012), anti-PanNa v (Ban, Smith, & Markham, 2015;Moore et al, 2009), and anti-TH (Fu et al, 2012;Henny et al, 2012;Hioki et al, 2010;Kantor et al, 2015), antibodies in every case.…”

Section: Antibody Characterizationmentioning

confidence: 99%

Characterization of the axon initial segment of mice substantia nigra dopaminergic neurons

González-Cabrera

Meza

Ulloa

et al. 2017

J of Comparative Neurology

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The axon initial segment (AIS) is the site of initiation of action potentials and influences action potential waveform, firing pattern, and rate. In view of the fundamental aspects of motor function and behavior that depend on the firing of substantia nigra pars compacta (SNc) dopaminergic neurons, we identified and characterized their AIS in the mouse. Immunostaining for tyrosine hydroxylase (TH), sodium channels (Na ) and ankyrin-G (Ank-G) was used to visualize the AIS of dopaminergic neurons. Reconstructions of sampled AIS of dopaminergic neurons revealed variable lengths (12-60 μm) and diameters (0.2-0.8 μm), and an average of 50% reduction in diameter between their widest and thinnest parts. Ultrastructural analysis revealed submembranous localization of Ank-G at nodes of Ranvier and AIS. Serial ultrathin section analysis and 3D reconstructions revealed that Ank-G colocalized with TH only at the AIS. Few cases of synaptic innervation of the AIS of dopaminergic neurons were observed. mRNA in situ hybridization of brain-specific Na subunits revealed the expression of Na 1.2 by most SNc neurons and a small proportion expressing Na 1.6. The presence of sodium channels, along with the submembranous location of Ank-G is consistent with the role of AIS in action potential generation. Differences in the size of the AIS likely underlie differences in firing pattern, while the tapering diameter of AIS may define a trigger zone for action potentials. Finally, the conspicuous expression of Na 1.2 by the majority of dopaminergic neurons may explain their high threshold for firing and their low discharge rate.

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Section: Antibody Characterizationmentioning

confidence: 99%

Characterization of the axon initial segment of mice substantia nigra dopaminergic neurons

González-Cabrera

Meza

Ulloa

et al. 2017

J of Comparative Neurology

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“…The sublayers are formed by the processes of retinal neurons synapsing with their partners in a well-organized and highly specific pattern. Recent publications distinguish 10–11 such strata 83,84 and evidence suggests that some of these layers are more vulnerable to diabetes than others. A damage or oedema of a specific sublayer may change the overall optical properties and reflectance of the IPL and therefore its thickness on OCT scans.…”

Section: Discussionmentioning

confidence: 99%

Detailed Evaluation of Possible Ganglion Cell Loss in the Retina of Zucker Diabetic Fatty (ZDF) Rats

Hajdú

Laurik

Szabó

et al. 2019

Sci Rep

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A thinning of the inner retina is one of the earliest potential markers of neuroretinal damage in diabetic subjects. The histological background is uncertain; retinal ganglion cell (RGC) loss and changes in the structure or thickness of the inner plexiform layer (IPL) have been suspected. Studies conducted on animal models on RGC pathology gave contradictory results. Hereby we present RGC numbers, distribution patterns and IPL thickness from Zucker Diabetic Fatty (ZDF) rats. After labelling RGCs on retinal whole mounts, isodensity maps were constructed, RGC numbers and distribution patterns analysed using a custom-built algorithm, enabling point-by-point comparison. There was no change in staining characteristics of the antibodies and no significant difference in average RGC densities was found compared to controls. The distribution patterns were also comparable and no significant difference was found in IPL thickness and stratification or in the number of apoptotic cells in the ganglion cell layer (GCL). Our results provide a detailed evaluation of the inner retina and exclude major RGC loss in ZDF rats and suggest that other factors could serve as a potential explanation for inner retinal thinning in clinical studies. Our custom-built method could be adopted for the assessment of other animal or human retinas.

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“…Kantor et al describe TNAP activity in the eye localized to vessels of the retina, the photoreceptor layer, and mostly in the outer and inner plexiform layers within many species [182]. TNAP/Tnap is present in the sublayers of the inner plexiform layer, especially in rats and zebrafish, respectively [182,183]. Nevertheless, to the best of our knowledge, no impairment concerning vision ability has been reported in the context of HPP patients so far, which may suggest the presence of a compensatory mechanism in the human eyes.…”

Section: Visual Perceptionmentioning

confidence: 99%

“…[168] [158] [166,167] Eye Expression in the retina is reported for a wide number of vertebrates and is evolutionary highly conserved. [183] [183]…”

Section: Neurons and Brainmentioning

confidence: 99%

Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease

et al. 2020

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Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the ALPL gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme’s role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.

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Stratified organization and disorganization of inner plexiform layer revealed by TNAP activity in healthy and diabetic rat retina

Cited by 8 publications

References 40 publications

Characterization of the axon initial segment of mice substantia nigra dopaminergic neurons

Characterization of the axon initial segment of mice substantia nigra dopaminergic neurons

Detailed Evaluation of Possible Ganglion Cell Loss in the Retina of Zucker Diabetic Fatty (ZDF) Rats

Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease

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