TNAP activity is localized at critical sites of retinal neurotransmission across various vertebrate species

Abstract

Evidence is emerging with regard to the role of tissue non-specific alkaline phosphatase (TNAP) in neural functions. As an ectophosphatase, this enzyme might influence neural activity and synaptic transmission in diverse ways. The localization of the enzyme in known neural circuits, such as the retina, might significantly advance an understanding of its role in normal and pathological functioning. However, the presence of TNAP in the retina is scarcely investigated. Our multispecies comparative study (zebrafish, cichlid, frog, chicken, mouse, rat, golden hamster, guinea pig, rabbit, sheep, cat, dog, ferret, squirrel monkey, human) using enzyme histochemistry and Western blots has shown the presence of TNAP activity in the retina of several mammalian species, including humans. Although the TNAP activity pattern varies across species, we have observed the following trends: (1) in all investigated species (except golden hamster), retinal vessels display TNAP activity; (2) TNAP activity consistently occurs in the photoreceptor layer; (3) in majority of the investigated species, marked TNAP activity is present in the outer and inner plexiform layers. In zebrafish, frog, chicken, guinea pig, and rat, TNAP histochemistry has revealed several sublayers of the inner plexiform layer. Frog, golden hamster, guinea pig, mouse, and human retinas possess a subpopulation of amacrine cells positively staining for TNAP activity. The expression of TNAP in critical sites of retinal signal transmission across a wide range of species suggests its fundamental, evolutionally conserved role in vision.

Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development

“…The lack of responsiveness to levamisole leads to the assumption that those organs express an intestinal (alpi.1 or alpi.2) instead of the tissue-nonspecific isoform of the AP (alpl). Additionally, the highest alpl expression levels along with strong AP-activity can be observed in the eyes, more precisely in the lens and the retina, which seems to be conserved between different vertebrate species and is in line with previously published literature 15 . However, no specific symptoms concerning the visual performance of HPP patients have been described so far and the exact role of TNAP/Tnap in the visual system and potential compensatory mechanisms remain to be unraveled in future experiments.…”

“… Tissue Primates Mouse Zebrafish Blood vessels + + + Retina + + + Forebrain Diencephalon (hypothalamus, thalamus) n.a + + Telencephalon (amygdala, olfactory bulb, cortex, hippocampus, septum, pallium) + + + Olfactory bulb n.a + n.a Midbrain Ventricular zones (e.g. DiV and TeV in the midbrain) + + + Septum n.a + + Hindbrain Medulla oblongata, metencephalon n.a + + References 6 , 13 – 15 , 59 – 62 15 , 16 , 18 , 57 , 60 , 63 , 64 MGI database: 87,983 15 own data n.a. : not available.…”

“…Additionally, TNAP enzyme supports the development and maintenance of synapse functionality and is involved in the outgrowth and myelination of neurites 10 – 12 . Localization of TNAP within primates’ brains has been described as distinct patterns within layer 4 and 5 of the cortex 13 , 14 and has been detected in the retina across a number of different vertebrate species 15 . In mice, TNAP localization was detected predominantly in endothelial cells, primordial germ cells, pioneer growth cones, and neural precursors 16 .…”

Tissue-nonspecific Alkaline Phosphatase Regulates Purinergic Transmission in the Central Nervous System During Development and Disease

“…It is of interest that the high activity of TNAP in the cortex coincides with the peak of synaptogenesis [55,56] , suggesting a functional involvement of TNAP in synapse formation and maturation. Recent studies demonstrated the presence of TNAP in the retina of several vertebral species, including humans, suggesting a role in retinal neurotransmission [57] . While the precise biological functions of TNAP at these CNS sites remain to be further elucidated, emerging evidence suggests that TNAP may act through metabolic pathways additional to hydrolyzing extracellular nucleotides.…”

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

“…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.…”