Denervation of rabbit lacrimal gland increases levels of transferrin and unidentified tear proteins of 44 and 36 kDa

Salvatore, Michael F.; Pedroza, Lia; Beuerman, Roger W.

doi:10.1076/ceyr.18.6.455.5270

Cited by 16 publications

(12 citation statements)

References 16 publications

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“…Blockade of adrenoceptors and cholinoceptors with the use of the corresponding antagonists did not alter the effect produced by adenine dinucleotides, in contrast to the partial reduction in basal tear secretion, as has been previously described (Salvatore et al, 1999). These results are consistent with the observation that P2Y 2 receptor gene expression is observed throughout the corneal and conjunctival epithelium, but not found in nerve terminals innervating the meibomian gland (Yerxa et al, 2000).…”

Section: Discussionsupporting

confidence: 81%

Effects of Diadenosine Polyphosphates on Tear Secretion in New Zealand White Rabbits

Pintor¹,

Peral²,

Hoyle³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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Extracellular diadenosine polyphosphates play important signaling functions in a number of physiological responses. Here we show that diadenosine polyphosphates are normal constituents of tear fluid and are potent stimulators of tear secretion through their interaction with P2Y receptors. Diadenosine tetraphosphate (Ap 4 A) and Ap 5 A were found in rabbit tears under basal conditions at concentrations of 2.92 and 0.58 M, respectively. Single applications of UTP, ATP, and Ap 4 A increased tear secretion to 160 Ϯ 8% (n ϭ 16) (P Ͻ 0.001), 131 Ϯ 6% (P Ͻ 0.05), and 162 Ϯ 11% (P Ͻ 0.05) of placebo values, respectively. Ap 4 A, Ap 5 A, and Ap 6 A, but not Ap 2 A and Ap 3 A, were able to stimulate tear secretion in a dose-dependent manner. Concentration-response studies produced pD 2 values of 5.56 Ϯ 0.03, 5.75 Ϯ 0.12, and 5.50 Ϯ 0.09 for Ap 4 A, Ap 5 A, and Ap 6 A, respectively, with Ap 4 A showing the greatest efficacy. Diadenosine polyphosphates also stimulated P2Y 1 and P2Y 2 receptors expressed in 1321N1 cells with no apparent effect on the other P2Y receptors tested. Nonselective P2 antagonists did not modify the tear secretion induced by UTP or Ap 4 A in rabbit eyes in vivo or in cloned receptors, except for a weak but significant reduction in stimulated tear secretion by reactive blue 2. These results suggest that diadenosine polyphosphates stimulate tear secretion via a P2Y receptormediated mechanism. Comparing the effects of diadenosine polyphosphates applied to the rabbit eye and to cloned P2Y receptors, it appears that the P2Y 2 receptor subtype is responsible for the prosecretory effects of these compounds.

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Section: Discussionsupporting

confidence: 81%

Effects of Diadenosine Polyphosphates on Tear Secretion in New Zealand White Rabbits

Pintor¹,

Peral²,

Hoyle³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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“…In the denervated glands there was a downregulation of genes for the Golgi apparatus and the endoplasmic reticulum, but an upregulation of genes for cytoskeletal and extracellular matrix components, inflammation, and apoptosis(Nguyen, Toshida et al 2004; Nguyen, Vadlamudi et al 2006). Furthermore, postganglionic denervation increased the concentration of three tear proteins one of which was identified as transferrin, in the lacrimal gland (Salvatore, Pedroza et al 1999). In a later study, in denervated animals, tear protein concentration was decreased consistent with decreased lacrimal gland secretion.…”

Section: Regulation Of Sensory Reflexes From the Ocular Surfacementioning

confidence: 99%

Neural regulation of lacrimal gland secretory processes: Relevance in dry eye diseases

Dartt

2009

Progress in Retinal and Eye Research

411

370

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The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins. The amount and composition of this layer is critical for the health, maintenance, and protection of the cells of the cornea and conjunctiva (the ocular surface). Small changes in the concentration of tear electrolytes have been correlated with dry eye syndrome. While the mechanisms of secretion of water, electrolytes and proteins from the lacrimal gland differ, all three are under tight neural control. This allows for a rapid response to meet the needs of the cells of the ocular surface in response to environmental conditions. The neural response consists of the activation of the afferent sensory nerves in the cornea and conjunctiva to stimulate efferent parasympathetic and sympathetic nerves that innervate the lacrimal gland. Neurotransmitters are released from the stimulated parasympathetic and sympathetic nerves that cause secretion of water, electrolytes, and proteins from the lacrimal gland and onto the ocular surface. This review focuses on the neural regulation of lacrimal gland secretion under normal and dry eye conditions.

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“…Numerous proteins have been detected in the tears such as lysosomal hydrolases (van Haeringen and Glasius, 1980), secretory IgA (van Haeringen, 1981), lactoferrin (Yoshino et al, 1997), transferrin (Salvatore et al, 1999) and growth factors (Van Setten et al, 1996). These tear proteins are largely produced by the acinar epithelial cells of the lacrimal gland.…”

Section: Introductionmentioning

confidence: 99%

Male NOD mouse external lacrimal glands exhibit profound changes in the exocytotic pathway early in postnatal development

Costa

Veigh

et al. 2006

Experimental Eye Research

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The lacrimal glands of male NOD mice exhibit many of the features of the human lacrimal gland in patients afflicted with the autoimmune disease, Sjögren's syndrome, including loss of secretory functions and lymphocytic infiltration into the lacrimal gland. To elucidate the early changes in the secretory pathway associated with development of Sjögren's syndrome, we investigated the organization of the exocytotic pathway in lacrimal glands of age-matched male BALB/c and NOD mice. Cryosections from lacrimal glands from 1 and 4 month male BALB/c and NOD mice were processed for confocal fluorescence and electron microscopic evaluation of different participants in exocytosis. No changes in apical actin filaments were noted in glands from NOD mice, but these glands exhibited thickening of basolateral actin relative to that seen in the BALB/c mice. Rab3D immunofluorescence associated with mature secretory vesicles was distributed abundantly in a continuous vesicular network concentrated beneath the apical plasma membrane in glands from 1 and 4 month BALB/c mice. In glands from 1 month NOD mice, rab3D immunofluorescence exhibited marked discontinuity and irregularity in the vesicular labeling pattern. While this change was also detected in glands from 4 month NOD mice, many of these glands exhibited an additional extension of rab3D labeling through the cell to the basolateral membrane. Electron microscopic analysis confirmed the formation of irregularly-shaped, unusually large secretory vesicles in lacrimal glands from NOD mice. Quantitation of multiple secretory vesicles from electron micrographs revealed a significant (p ≤5) increase in the percentage of secretory vesicles incorporated into multivesicular aggregates in lacrimal glands from 1 and 4 month NOD mice compared to BALB/c mice. The M3 muscarinic receptor, a key signaling effector of exocytosis, was redistributed away from its normally basolateral locale in glands from BALB/c mice, with concomitant enrichment in intracellular aggregates in glands from NOD mice. These findings show that lacrimal glands in NOD mice as young as 1 month contain aberrant secretory vesicles with altered effector composition that undergo premature cytoplasmic fusion, and that changes in the distribution of the M3 muscarinic receptor occur within the same time frame.

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Denervation of rabbit lacrimal gland increases levels of transferrin and unidentified tear proteins of 44 and 36 kDa

Cited by 16 publications

References 16 publications

Effects of Diadenosine Polyphosphates on Tear Secretion in New Zealand White Rabbits

Effects of Diadenosine Polyphosphates on Tear Secretion in New Zealand White Rabbits

Neural regulation of lacrimal gland secretory processes: Relevance in dry eye diseases

Male NOD mouse external lacrimal glands exhibit profound changes in the exocytotic pathway early in postnatal development

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