Intranasal self-administration of high-pressure physiological saline isotonic solution ameliorates dry eye symptoms and tear film composition: a pilot study.

OBJECTIVE: High-pressure physiological saline isotonic solution (HPpSIS) delivery into the nasal cavity was found to modulate the local expression of immune cells, increase NGF protein, and enhance the NGF receptors' expression. Since the nasal cavity directly communicates with the eye and as NGF was previously found to ameliorate the symptoms of dry eye when topically delivered, the aim of this study was to establish whether the HPpSIS might ameliorate ocular dryness and tear film composition. SUBJECTS AND METHODS: This is an observational self-controlled case study carried out on 16 patients with dry-eye diagnosis, concerning 3-month self-administration of HPpSIS and two serial assessments of the ocular surface and tear film. OSDI questionnaire was used for ocular symptoms of dryness. BUT and Schirmer tests were used for qualitative and quantitative tear film analysis. The lipid composition was also examined. R-studio was employed for the detection of the difference between the pre- and post-analysis. RESULTS: On the basis of the OSDI questionnaire, the study population was divided into severe (61.1%), moderate (5.5%), and mild (16.6%) dry-eye symptoms. OSDI score was significantly reduced after HPpSIS (p<0.05). BUT and TMH values also ameliorated after HPpSIS (p>0.05), although not significantly. The lipid layer improved statistically (p<0.05) and correlated positively with OSDI grading. The variability of presentation in the numerical distribution before and after therapy suggests poor test sensitivity. CONCLUSIONS: HPpSIS showed a positive effect in reducing OSDI scores and ameliorating tear film quality. The possibility of an endogenous HPpSIS-induced NGF should be taken into account in dry-eye therapy.

Antiviral effect of high-pressure nasal stimulation.

OBJECTIVE: In a previous study, we reported an increase of nasal nerve growth factor (NGF) in patients treated with high-pressure administration of sterile saline isotonic solution (HPpSIS). Herein we characterized the nasal mucosa in terms of innate immune response and cytokine signature, including antiviral properties. Potential NGF and antiviral benefits of HPpSIS were also discussed. PATIENTS AND METHODS: Twenty (20) patients (11 males, 9 females; age range 30-75 years old) underwent HPpSIS and nasal samples were collected before and after treatment. Nasal scraping was used for morphological (smears and Quick May-Grunwald Giemsa staining, MGG), biochemical (Histamine, Serotonin; ELISA) and molecular (messenger RNA, mRNA) analyses. Amplification of transcripts specific for Toll-like receptor (TLR) 3 (TLR3), TLR7, TLR9, Interleukin-(IL) 18 (IL18), IL13, IL12, eosinophil-derived neurotoxin (EDN), Eosinophil Cationic Protein (ECP), γ Interferon (γIFN), tryptase and serotonin was performed using the 2-step real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR). Clinical and laboratory data were analyzed and compared. RESULTS: The clinical evaluation showed a protective effect of our therapy. Smears showed the presence of leucocytes, eosinophils (EOs) and mast cells (MCs), and increased immunoreactivity for ECP/RNase3 and EDN after HPpSIS. ELISA showed increased levels of Serotonin and EDN associated with unchanged levels of substance P(SP) and histamine. Increased eosinophil-derived neurotoxin eosinophil-derived neurotoxin (EDN) levels were confirmed by in situ fluorescent analysis. HPpSIS induced the upregulation of TLR3, TLR7 and TLR9 transcripts, while no changes were observed for Intercellular Adhesion Molecule 1 (ICAM1), IL18, Interleukin-15 (IL15) and IL12 transcripts nor for Interleukin-6 (IL6) and IL13. No changes were also observed for γIFN and EDN/RNase2 transcripts, while ECP/RNase3 transcripts were significantly upregulated after HPpSIS. Finally, tryptase transcripts were unchanged while serotonin transcripts were significantly increased after HPpSIS. CONCLUSIONS: The clinical and biomolecular changes observed at the nasal mucosa due to HpSS treatment suggest the activation of an innate surveillance, by means of TLR transcription, and a possible anti-viral response due to EDN upregulation. It remains to be verified if NGF, known to be released locally upon HpSIS treatment, might in part be responsible for this local activation.

Current progress of Reelin in development, inflammation and tissue remodeling: from nervous to visual systems.

Reelin is a matrix glycoprotein that plays a pivotal role for the positioning of neurons throughout brain development. In the early developing cortex Reelin regulates radial migration of cortical neurons while later in development, Reelin promotes maturation of dendrites and dendritic spines. Low Reelin levels characterize healthy adult brain while increased Reelin levels have been associated with cellular events underlying response to injury. Reelin has been detected in structural and immune cells outside brain (liver, gut/colon tracts, kidney, testis, ovary, lung, retina and cornea). In the Visual system, Reelin was first described in the retina and thereafter in the cornea. Increased Reelin levels were observed during retinogenesis, low levels were found in adulthood and a significant increase was detected upon injury. Insult-driven Reelin changes occur after upregulation of adhesion molecules, cytokines, neurotrophins, growth factors, neuropeptides and other mediators as well as their receptors. These soluble factors contribute to the development of nervous and visual system and promote survival/recovery of neurons/accessory cells populating the injured visual system. Likewise, Reelin might modulate these factors by driving different multiple effects on homeostasis/plasticity, inflammation, healing and remodeling at different physiopathological levels. Very low-density lipoprotein receptor, apolipoprotein E receptor 2, integrins and the adaptor molecule Disabled 1 trigger Reelin. Recent advances highlight some Reelin activities during inflammation and tissue remodeling and point out to a crucial Reelin activity in the visual system. A better understanding of Reelin function in retinal development might open to new attractive perspective for counteracting retina degeneration.