vasoactive-intestinal-peptide and Keratoconjunctivitis-Sicca

Histopathological parameters of the main lachrymal gland from patients with primary Sjögren's syndrome (SS1) were investigated, and the relation between morphological and immunohistochemical changes in the innervation of lachrymal gland in patients with SS1, as well as the immunopathological differences between SS1, non-autoimmune keratoconjunctivitis sicca (KCS) and controls were analysed.. Lachrymal glands from patients with SS1, KCS and control subjects were biopsied and examined using standard transmission electron microscopic techniques and an immunohistochemical method (vasoactive intestinal polypeptide-VIP).. Moderate numbers of myelinated and non-myelinated nerve fibres were found in the connective tissue around lachrymal glands in patients with SS1. Non-myelinated nerve fibres made contact with glandular epithelium, myoepithelial cells, vascular endothelium, plasma cells and fibroblasts. Patients with non-immunological KCS had similar characteristics as SS1 in number and activity, showing a normal morphological pattern. Control subjects showed a higher number of active nerve fibres.. Main lachrymal gland from patients with SS1 were therefore definitively innervated with moderate activity and normal structures. The ultrastructural study demonstrated there were no statistical differences with respect to patients with non-autoimmune KCS. Immunohistochemical studies showed a similar VIP activity in lachrymal gland between patients with SS1 and KCS, but there was a significant decrease in the innervation activity with regard to control subjects. All this implies that the autoimmunological factor in patients with SS1 does not significantly affect the lachrymal gland innervation.

Topics: Adult; Aged; Aged, 80 and over; Female; Fluorescent Antibody Technique, Indirect; Humans; Keratoconjunctivitis Sicca; Lacrimal Apparatus; Male; Middle Aged; Nerve Fibers; Parasympathetic Nervous System; Sjogren's Syndrome; Vasoactive Intestinal Peptide

The authors examined the effect of topical application of agents known to increase cyclic nucleotide levels on tear secretion by accessory lacrimal gland tissue in their rabbit model for keratoconjunctivitis sicca (KCS). Tear secretion was studied by changes in tear film osmolarity and tear volume caused by application of the agents relative to application of isotonic buffer solution alone. A decrease in tear film osmolarity or increase in tear volume was interpreted as an increase in tear secretion. Irritative stimulation was distinguished from pharmacologic stimulation by the prior use of topical proparacaine. The following agents significantly decreased tear film osmolarity and increased tear volume: vasoactive intestinal peptide (2 X 10(-8) to 2 X 10(-6) M); three pro-opiomelanocortin fragments alpha-, beta-, and gamma-melanocyte stimulating hormone at 10(-4), 10(-3), and 10(-3) M, respectively; the permeable cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) analogs 8-Br cAMP (0.3-3.0 X 10(-3) M) and 8-Br cGMP (1.0-10.0 X 10(-3) M); and the cyclic nucleotide phosphodiesterase inhibitor 1-isobutyl-3-methyl xanthine (0.3-3.0 X 10(-3) M). Forskolin (2 X 10(-4) M), which activates the catalytic subunits of adenyl cyclase, increased tear volume significantly. Secretin, adrenocorticotropic hormone, and pilocarpine were ineffective. The authors conclude that agents that increase either cAMP or cGMP levels pharmacologically stimulated tear secretion when applied topically to rabbit eyes with surgically induced KCS.

Topics: Administration, Topical; Animals; Colforsin; Disease Models, Animal; Female; Keratoconjunctivitis; Keratoconjunctivitis Sicca; Lacrimal Apparatus; Male; Nucleotides, Cyclic; Ophthalmic Solutions; Osmolar Concentration; Phosphodiesterase Inhibitors; Pilocarpine; Pro-Opiomelanocortin; Rabbits; Signal Transduction; Tears; Vasoactive Intestinal Peptide